Sentinel Lymph Node Localisation With an Ultra-low Dose of Superparamagnetic Iron Oxide Nanoparticles in Patients With Breast Cancer
Phase: PHASE2
Conditions: Breast Cancer, Sentinel Lymph Node
Sponsor: Vastra Gotaland Region

Sponsor: Sahlgrenska University Hospital 
Protocol: MagSnow 2.0 version 1.2 2023-02-26 
 
 
 
                              
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Sentinel lymph node localisation with an ultra-low 
dose of superparamagnetic iron oxide nanoparticles 
in patients with breast cancer 
 
Protocol: SUGBG-2022002 
Version: 1.2 2023-02-26 
Sponsor: Sahlgrenska University Hospital 
Principal Investigator: Fredrik Wärnberg 
 
 

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1 SIGNATURES 
1.1 Principal investigator’s Agreement 
 
This confidential document is the property of the sponsor. No unpublished information 
contained in this document may be disclosed without prior written approval of the sponsor. I 
have read the attached protocol entitled ”Sentinel lymph node localisation with an ultra-low 
dose of superparamagnetic iron oxide nanoparticles in patients with breast cancer”, and agree 
to abide by all provisions set forth therein. 
 
I agree to comply with the International Conference on Harmonization (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP), ISO14155, and applicable national or regional 
regulations/guidelines. 
 
I agree to ensure that Financial Disclosure Statements will be completed by: 
• me (including, if applicable, my spouse [or legal partner] and dependent children) 
• my co-investigators (including, if applicable, their spouses [or legal partners] and dependent 
children) at the start of the study and for up to one year after the study is completed, if there 
are changes that affect the financial disclosure status. 
 
 
 
------------------------------- 
Signature 
 
Fredrik Wärnberg 
-------------------------------- 
 
 
-------------------------------- 
Principal investigator  
 
 
Date (DD Month YYYY) 
Department of Surgery 
Sahlgrenska University Hospital 
SE-413 45 Gothenburg, Sweden 
 
 

Sponsor: Sahlgrenska University Hospital 
Protocol: MagSnow 2.0 version 1.2 2023-02-26 
 
 
 
                              
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1.2 Sponsor´s agreement 
 
I approve the attached protocol entitled ”Sentinel lymph node localisation with an ultra-low 
dose of superparamagnetic iron oxide nanoparticles in patients with breast cancer”, and agree 
that the study is conducted at the Department of Surgery, Sahlgrenska University Hospital, 
Sweden. 
 
 
 
 
 
------------------------------- 
Signature 
 
Erik Johnsson  
-------------------------------- 
 
 
-------------------------------- 
Chair, Department of Surgery 
 
Date (DD Month YYYY) 
Sahlgrenska University Hospital 
SE-413 45 Gothenburg, Sweden 
 

Sponsor: Sahlgrenska University Hospital 
Protocol: MagSnow 2.0 version 1.2 2023-02-26 
 
 
 
                              
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2 INVESTIGATORS 
2.1 Principal investigators 
Fredrik Wärnberg 
Department of Surgery, Sahlgrenska University Hospital, 
Gothenburg 
2.2 Co-investigators  
Nushin Mirzaei 
Department of Surgery, Sahlgrenska University Hospital, 
Gothenburg 
Roger Olofsson Bagge 
Department of Surgery, Sahlgrenska University Hospital, 
Gothenburg  
Henrik Leonhardt 
Department of Radiology, Sahlgrenska University Hospital, 
Gothenburg 
Pontus Zaar 
Department of Radiology, Sahlgrenska University Hospital, 
Gothenburg 
Andreas Karakatsanis 
Department of Surgery, Uppsala Academic Hospital, Uppsala 
 
Staffan Eriksson 
Department of Surgery, Västmanland´s Central Hospital 
Västerås 
Eva Vikhe Patil 
Department of Surgery, Linköping University Hospital, 
Linköping 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
1 
Signatures ............................................................................................................................ 2 
1.1 
Principal investigator’s Agreement ........................................................................................ 2 
1.2 
Sponsor´s agreement ............................................................................................................. 3 
2 
Investigators ........................................................................................................................ 4 
2.1 
Principal investigators ............................................................................................................ 4 
2.2 
Co-investigators ..................................................................................................................... 4 
3 
List of abbreviations and key terms ....................................................................................... 7 
3.1 
List of abbreviations ............................................................................................................... 7 
3.2 
List of key study terms ............................................................................................................ 8 
4 
Synopsis ............................................................................................................................... 9 
5 
Introduction ........................................................................................................................10 
5.1 
Background .......................................................................................................................... 10 
6 
Study objectives and design .................................................................................................10 
6.1 
Study Objectives ................................................................................................................... 11 
6.2 
Study endpoints .................................................................................................................... 11 
6.3 
Risk benefit evaulation ......................................................................................................... 11 
6.4 
Study design and procedures………………………………………………………………………………………….. 12 
6.4.1 
Overall study design…………………………………………………………………………………………………… 12 
6.4.2 
Procedures ....................................................................................................................... 12 
6.4.3 
Flow-chart/time and events schedule ............................................................................. 12 
7 
Study population .................................................................................................................13 
7.1 
Inclusion criteria ................................................................................................................... 13 
7.2 
Exclusion criteria .................................................................................................................. 13 
7.3 
Subject enrolment ................................................................................................................ 13 
7.4 
Discontinuation criteria for individual subjects .................................................................... 13 
7.5 
Premature termination of the study .................................................................................... 13 
8 
Study Treatments ................................................................................................................14 
8.1 
Description of investigational product(s) ............................................................................. 14 
8.2 
Dose and administration ...................................................................................................... 14 
8.3 
Packaging, labeling, and handling of investigational products(s) ....................................... 14 
9 
Safety and tolerability .........................................................................................................16 
9.1 
Investigational device .......................................................................................................... 16 
9.1.1 
Adverse Event (AE) .......................................................................................................... 16 
9.1.2 
Serious Adverse Event (SAE) ............................................................................................ 16 
9.1.3 
Device deficiency.Unanticipated Adverse Device Effect (UADE)..................................... 17 
9.1.4 
Unanticipated Adverse Device Effect (UADE)………… ....................................................... 17 
9.1.5 
Causality…………………………………………………………………………………………………………………….  17 
9.1.6 
Reporting ………………………………………………………………………………………………………………….. 18 
10 
Termination of the clinical study ..........................................................................................19 
11 
Statistics .............................................................................................................................19 
11.1 
Statistical methods ............................................................................................................... 19 
11.2 
Drop-outs ............................................................................................................................. 20 
12 
Operational and administrative considerations 

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12.1 
Procedure for clinical study quality control .......................................................................... 20 
12.1.1 Data Collection ................................................................................................................ 20 
12.1.2 Data Management ........................................................................................................... 20 
12.1.3 Specification of Source Documents ................................................................................. 20 
12.1.4 Direct Access to Source Data/Documents ....................................................................... 21 
12.1.5 Data Storage and Management....................................................................................... 20 
12.2 
Clinical Study Monitoring ..................................................................................................... 22 
12.3 
Audits and Inspections ......................................................................................................... 23 
12.4 
Deviations from clinical investigation plan .......................................................................... 24 
12.5 
Ethics and protection of subject confidentialityublications ................................................. 24 
12.5.1 Independent Ethics Committee ....................................................................................... 21 
12.5.2 Protocol Amendment and/or Revision ............................................................................ 21 
12.5.3 Ethical Conduct of Study .................................................................................................. 22 
12.5.4 Informed Consent of Subjects ......................................................................................... 22 
12.5.5 Subject Confidentiality............................................................. ……………………………………..22 
12.6 
Administrative matters ........................................................................................................ 24 
12.6.1 Arrangement for Use of Information and Publication of the Clinical Study.................... 22 
12.6.2 Documents and Records Related to the Clinical Study ................................................... 23 
12.7 
Economics ............................................................................................................................ 24 
12.8 
Publications .......................................................................................................................... 24 
12.9  
Insurance .............................................................................................................................. 24 
13 
Study organization ..............................................................................................................24 
14 
References ..........................................................................................................................24 
 
 

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3 LIST OF ABBREVIATIONS AND KEY TERMS 
3.1 List of abbreviations 
AE 
Adverse Event 
CT  
Computed Tomography 
EC 
Ethics Committee 
CRF  
Case Report Form 
GCP 
Good Clinical Practice 
IB 
Investigators Brochure  
MDR 
Medical Device Regulation 
MPA 
Medical Products Agency 
MRI  
Magnetic Resonance Imaging 
PMCF 
Post Market Clinical Follow-up 
SAE 
Serious Adverse Event 
SDIEQ  
Skin Discoloration Impact Evaluation Questionnaire 
SLN 
Sentinel Lymph Node 
SLNB 
Sentinel Lymph Node Biopsy 
SOC  
Standard of Care 
SPC 
Summary of Product Characteristics 
SPIO 
Superparamagnetic nanoparticles of Iron Oxide 
Tc99m 
Technetium99m 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 
 

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3.2 List of key study terms 
Terms 
Definition of terms 
Investigational period  
Period of time where major interests of protocol objectives related 
to defined endpoints are observed, and usually where the test 
device or comparative device (sometimes without randomization) 
is given to a subject and continues until the last observation after 
completing administration of the test device or comparative device. 
 
Treatment number 
Number assigned to each subject who has completed all screening 
assessments successfully at baseline and is willing to be included in 
the study. 
 
Enrolled subject 
Subjects included in the study. 
 
Source data  
All information in original records and certified copies of original 
records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the 
trial. Source data are contained in source documents (original 
records or certified copies). 
 
Source documents 
Original documents, data, and records including source data. 
 
Subject  
An individual who participates in a clinical trial, including 
screening but not necessarily given study device (enrolment).  
 
Withdrawal 
Subject enrolled but did not complete the study for any reason. 
 
 
 

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4 SYNOPSIS 
Title of Study 
Sentinel lymph node localisation with an ultra-low dose of 
superparamagnetic iron oxide nanoparticles in patients with breast 
cancer 
Planned Study 
Period 
4 years, 6 months 
Enrolment period: 18 months (Q1/2023 – Q3/2024). Follow-up 
period: 3 years (Q3/2024 – Q3/2027) 
Study 
Objective(s) 
The overall aim is to demonstrate that the use of superparamagnetic 
iron oxide nanoparticles (SPIO) as a tracer in an ultra-low dose 
(0.1ml) is non-inferior for sentinel lymph node (SLN) detection in 
patients with breast cancer compared to the dual technique using 
Tc99m +/- blue dye, and to evaluate MRI breast artefacts and skin 
staining over time.  
Primary objective: 
To compare SLN detection rates between Magtrace® 0.1ml 
and the dual routine technique with radioactive tracer 
(Technetium99m, Tc99) +/- blue dye 
Secondary objectives: 
A. To follow MRI breast artefacts for two years 
B. To follow SPIO and blue dye skin staining for three years 
Design and 
Methodology 
A prospective cohort study where all research persons have a SLN 
biopsy using both SPIO and the dual technique 
Number of 
Subjects Planned 
220 patients, based on a non-inferiority design with a 4% margin with 
each patient being their own control 
Endpoints 
Primary endpoint: 
SLN detection rate for Magtrace® 0.1ml and for the dual technique 
(Tc99 +/- blue dye) measured as per cent of patients where a SLN is 
identified using either the magnetic or the dual technique 
Secondary endpoints: 
A. MRI Magtrace® artefacts at 3-6, 12 and 24-36 months 
postoperatively measured as per cent of patients with remaining 
artefacts evaluated by blinded central review. 
 
B. Skin staining due to injected Magtrace® and blue dye at 4 weeks, 
12, 24 and 36 months measured as per cent of patients with 
remaining brown or blue skin staining and stain size, evaluated 
by the investigator and the Skin Discoloration Impact 
Evaluation Questionnaire (SDIEQ) 
 
C. Rate of device-related AEs and SAEs 
 
D. Numbers of nodes detected and removed for Magtrace® 0.1ml 
and for the dual technique (Tc99 +/- blue dye) 
 
E. Concordance between detected sentinel lymph nodes by 
Magtrace® 0.1ml or by the dual technique (Tc99 +/- blue dye)  
 

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Selection 
Criteria 
Inclusion Criteria 
1. Age above 18 years 
2. Planned for sentinel lymph node biopsy at (or after) breast 
surgery 
3. Signed and dated written informed consent before the start of 
specific protocol procedures 
Exclusion Criteria  
1. Pregnant or breast-feeding 
2. Iron overload disease 
3. Known hypersensitivity to iron, dextran compounds or blue dye. 
4. Inability to understand given information and give informed 
consent or undergo study procedures 
Discontinuation 
Criteria 
 
Subjects must be discontinued from the study for the following 
reasons: 
1. Inappropriate enrolment (violation of Inclusion / Exclusion 
Criteria) 
2. Withdrawal of consent 
3. Due to safety reasons judged by the Investigator 
5 INTRODUCTION 
5.1 Background 
Breast cancer is the most frequent cancer in women with approximately 10,000 new patients 
in Sweden yearly (The National Board of Health and Welfare of Sweden, 
www.socialstyrelsen.se). The sentinel lymph node (SLN) is the first lymph node that receives 
lymphatic drainage from the primary tumour site. Sentinel lymph node biopsy (SLNB) is an 
established technique for tumour staging in breast cancer patients [1]. The SLN is usually 
detected by the dual technique of injecting a radioactive isotope (Technetium99m, Tc99) and a 
blue dye (Patent bleu®) in the breast. The SLN is identified by a handheld gamma-probe and 
the dye stains the SLN with a blue colour which makes it easy to visualize during surgery. 
 
A new SLN tracer containing superparamagnetic nanoparticles of iron oxide 
(SPIO/Magtrace®) has shown similar detection rates as for the dual technique [2-4]. Magtrace 
has been injected interstitially (intra/peri-tumourally or subcutaneously behind the areola) 
before surgery and the SLNs are detected during surgery with a handheld probe (SentiMag®) 
that measures the strength of the magnetic field created by the magnetic tracer. 
 
After the use of SPIO/Magtrace® in breast cancer there is a risk of magnetic resonance 
imaging (MRI) artefacts after breast conserving surgery, as well as a risk for long-lasting skin 
staining after the injection. A feasibility study in melanoma, the MAGMEN study, have 
reported promising results using a ultra-low dose of 0.1 mL Magtrace®, that was injected 
intradermally [5]. In a feasibility study including 30 patients with breast cancer, we have 
shown that the SLN was detected in all 30 patients with a similar intradermal injection of 
0.1ml SPIO/Magtrace® (results not yet published). This ultra-low dose of Magtrace® would 
potentially reduce the drawbacks of SPIO related MRI artefacts and skin staining. 

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6 STUDY OBJECTIVES AND DESIGN 
6.1 Study objectives 
The overall aim is to evaluate the use of superparamagnetic iron oxide nanoparticles (SPIO) 
as a tracer in an ultra-low dose (0.1ml) is non-inferior for sentinel lymph node (SLN) 
detection in patients with breast cancer compared to the dual technique using Tc99m and blue 
dye, and to evaluate MRI breast artefacts and skin staining over time.  
 
Primary objective: 
SLN detection rate for Magtrace® 0.1ml and for the dual technique (Tc99 +/- blue 
dye) measured as per cent of patients where a SLN is identified using either the 
magnetic or the dual technique 
Secondary objectives: 
A. To follow MRI breast artefacts for two to three years 
B. To follow SPIO and blue dye skin staining for three years 
6.2 Study endpoints 
 
Primary endpoint: 
SLN detection rate for Magtrace® 0.1ml and for the dual technique (Tc99 +/- blue dye) 
measured as per cent of patients where a SLN is identified using either the magnetic or 
the dual technique 
 
Secondary endpoints: 
A. MRI Magtrace® artefacts at 3-6, 12 and 24-36 months postoperatively measured as per 
cent of patients with remaining artefacts evaluated by blinded central review. 
 
B. Skin staining due to injected Magtrace® and blue dye at 4 weeks, 12, 24 and 36 
months measured as per cent of patients with remaining brown or blue skin staining 
and stain size, evaluated by the investigator and the Skin Discoloration Impact 
Evaluation Questionnaire (SDIEQ)[8] 
 
C. Rate of device-related AEs and SAEs 
 
D. Numbers of nodes detected and removed for Magtrace® 0.1ml and for the dual 
technique (Tc99 +/- blue dye) 
 
E. Concordance between detected sentinel lymph nodes by Magtrace® 0.1ml or by for the 
dual technique (Tc99 +/- blue dye) 
6.3 Risk-benefit evaluation 
The magnetic technique is already approved for SLN diagnostics in breast cancer. The results 
are comparable to the clinically routine use of Tc99 and blue dye. The risk of using a lower 
dose of Magtrace® is that the SLN is not detected. An ultra-low dose of Magtrace® for 
identifying the SLN has been explored in a feasibility study with 30 patients and in all 
patients the SLN was detected. Also, in this study Tc99 +/- blue dye will be used in parallel as 
a comparison and back up minimising the risk of an unsuccessful SLNB.  
 

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For the study participants the study will result in an extra injection that can be painful but 
only for a short time. Skin staining from the Magtrace® can occur but as Magtrace® is 
currently used as a routine tracer in Sweden in a ten times higher dose, the benefit of testing a 
lower dose is greater than the risk of a small skin staining. The skin staining is also one of the 
outcomes that will be followed. 
 
In a subgroup of included persons, two to three breast MRIs will be performed after 3-6, 12 
and 24-36 months. MRI is painless and does not cause ionising radiation, but some people 
find the tight space discomforting. This part of the study is optional and up to the research 
person´s. The magnetic field could affect metal objects which are inside the body. Therefore, 
persons with surgical implants (e.g., insulin pump, or pacemaker) will be excluded from this 
part of the study.  
 
Participating in the study also takes extra time and personal data is to be handled. The risk of 
breaking their integrity is considered as small in this study. All patients are given information 
about both the benefits and risks of the research. They can then voluntarily decide whether 
they want to participate or not, and they can withdraw their consent at any time. 
 
In summary, the risk of being included in this trial is assessed to be low, and we have not 
identified any ethical problem in a broader perspective. The study participants contribute to 
advancing research on SLN and staging technology, which may be useful for other patients in 
the future. 
6.4 Study design and procedures 
6.4.1 Overall study design 
This is a prospective cohort study comparing an ultra-low dose of 0.1 mL Magtrace® with the 
dual technique with Tc99 +/- blue dye for SLN detection with a non-inferiority design. There 
is no randomisation but instead every person is their own control, i.e., the patient will have the 
SLN identified with both tracer methods. This study design has already been used in several 
international studies and 220 persons will be included at four study sites, during 18 months. 
Skin staining will be documented at the first follow up at four weeks with measurements of 
size of staining performed and documented with a photograph if staining is present for either 
SPIO or blue dye. Skin staining will be followed for three years after surgery. Those with a 
remaining skin staining at the routine 12 months follow up will be followed by telephone 
interview or physical visit at 24 and 36 months. 
Furthermore, up to 50 persons will be included for secondary objective A, for evaluation of 
MRI artefacts in the operated breast at 3-6, 12, and 24 months. All MRI and corresponding 
mammograms will be evaluated centrally regarding artefacts and breast density.  
6.4.2 Procedures 
An intradermal dose of 0.1ml Magtrace® will be injected up to 30 days before surgery. The 
injection should be in the skin over the tumour, or at the border of the areola. A pre-operative 
photo of the breast will be taken, including any staining. 

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Before surgery Tc99 is injected in the breast as per routine practice. Blue dye is optional and if 
used, it is injected after induction of anaesthesia. During surgery, SLNs are first identified 
with the SentiMag®-probe. The dual technique, with the gamma probe +/- blue dye will be 
used afterwards, confirming each removed SLN and for detection of additional SLNs. For 
each tracer, the following parameters will be recorded in the CRF: transcutaneous magnetic 
and radioactive signals in breast and axilla, number of nodes, the colour of the nodes, signals 
in vivo and ex vivo for each SLN, residual transcutaneous signals at the end of surgery in 
breast and axilla. A lymph node is considered a SLN if it contains more than a 10% activity 
compared to the maximum activity of the highest scoring lymph node (first SLN) with either 
tracer. Each SLN will be sent separately for routine histopathology with the specific question 
concerning microscopically detected SPIO. For all patients, the pathologists are requested to 
report the lymph node status separately. 
 
At the first post-operative visit (approximately 4 weeks after surgery) blue and brown skin 
staining will be recorded by photography including a centimetre scale, and any residual 
magnetic signal will be measured in the breast. In those patients with a remaining skin 
staining this procedure will be repeated at 12 months, and after 24 and 36 months by 
telephone interview without a photo or a physical visit. Patients will be asked about how they 
experience the staining according to a 5-point Likert scale (Skin Discoloration Impact 
Evaluation Questionnaire (SDIEQ))[8]. 
 
In up to 50 patients, a postoperative routine MRI of the breast, with contrast medium will be 
performed at 3-6, 12 and 24-36 months after surgery to evaluate the presence of SPIO 
artefacts. MRI artifacts and mammographic density will be recorded in a separate CRF by the 
radiologists and then transferred to our CRF. 
6.4.3 Flow-chart/time and events schedule 
*Optional, **One MRI between 24 and 36 months, a Follow up is ended when the stain is gone. bMagtrace injection 
0-30 days before surgery. 
 
Screening 
Day 
Week 
Months 
 
 
-30 to 0 
0 
4 +/-2 
3-6 +/-1 
12 
24 
36 
Eligibility 
assessments 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
Clinical Procedures 
 
 
 
 
 
 
 
 
Photographya 
X 
 
 
X 
 
X 
X* 
X* 
Administration of 
Magtraceb 
 
X 
 
 
 
 
 
 
Administration of 
Tc99 +/- blue dye 
 
 
X 
 
 
 
 
 
Surgery 
 
 
X 
 
 
 
 
 
Residual magnetic 
activitya 
 
 
X 
X 
 
X 
X 
X 
MRI breast* 
 
 
 
 
X 
X 
X** 
X** 

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7 STUDY POPULATION 
Patients planned for breast surgery and SLNB, will be considered for enrolment. 
7.1 Inclusion criteria 
1. Age above 18 years 
2. Planned for sentinel lymph node biopsy at (or after) breast surgery 
3. Signed and dated written informed consent before the start of specific protocol 
procedures 
7.2 Exclusion criteria 
A patient meeting ANY of the following criteria is not eligible for study participation: 
1. Pregnant or breast-feeding 
2. Iron overload disease 
3. Known hypersensitivity to iron, dextran compounds or blue dye. 
4. Inability to understand given information and give informed consent or undergo study 
procedures 
7.3 Subject enrolment 
Subject eligibility will be established before enrolment. Subjects will be enrolled strictly 
sequentially, as subjects are eligible for study participation. After enrolment the subject will 
be given a unique subject number per site, consisting of three letters for the study, the 
following three letters for the site and then a lot number, i.e., MAGGBG001. If a subject 
discontinues from the study, the subject number will not be reused, but the subject may be 
replaced.   
7.4 Discontinuation criteria for individual subjects 
The subject is free to withdraw from the study for any reason and at any time without giving 
reason for doing so and without penalty or prejudice to their treatment. The investigator is 
also free to terminate a subject’s study treatment at any time if the subject’s clinical condition 
warrants it. 
 
Discontinuation Criteria for Individual Subjects: 
Subjects must be discontinued from the study for the following reasons: 
1. Inappropriate enrolment (violation of Inclusion / Exclusion Criteria) 
2. Withdrawal of consent 
3. Due to safety reasons judged by the Investigator. 
 
The reasons for discontinuation should be recorded in the case report form (CRF). Persons 
discontinued from the study will be asked to return for an “End of Treatment Visit” and will 
thereafter be taken care of and followed at the discretion of the treating physician. Persons 
who discontinue the study will be replaced. Data collected up to the moment of withdrawal 
will be a part of the study analysis if accepted by the person. 
7.5 Premature termination of the study 
The sponsor has the right to terminate the trial prematurely if there are any relevant medical 
or ethical concerns, or if completing the trial is no longer feasible. If such action is taken, the 
investigator must inform all subjects and ensure appropriate care and follow up. The reasons 

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for terminating the trial must be documented in detail and the Ethics Committee must be 
given a written explanation.  
 
Premature termination of the trial will be considered if: 
1. The risk-benefit balance for the trial subjects’ changes markedly. 
2. The sponsor considers that the trial must be discontinued for safety reasons. 
3. Due to futility 
8 STUDY TREATMENTS 
8.1 Description of investigational product(s) 
Magtrace® (Endomagnetics Limited) is the magnetic tracer that is intended and calibrated for 
use with the SentiMag® device to identify SLN. It is a blackish-brown sterile suspension of 
SPIOs coated with carboxydextran, in a saline solution, with an iron concentration of 
28mg/ml. The carboxydextran coating prevents agglomeration while maintaining 
biocompatibility. The Z-averaged particle diameter, including the organic coating, is 60nm 
(<0.25 polydispersity). The diameter enables the SLNs to selectively filter out the particles. 
After injection the particles drain naturally to the lymph nodes via the lymphatic system 
where they are physically filtered, trapped, and accumulate. This allows them to be used as a 
lymph node marker, which can be identified by the SentiMag® device. Magtrace® can be 
injected up to 30 days before SLNB. There is no evidence of anaphylaxis with interstitial 
tracer injection. Sentimag and Magtrace are CE-approved for SLN localisation. 
 
Tc99 consists of a sterile aqueous suspension of Technetium-99m labelled to human albumin 
aggregate particles and is used for radioactive detection of sentinel nodes. Blue dye, (Bleu 
Patenté V Sodique Guerbet, 25mg/ml) is a blue dye that is approved for use as a sentinel node 
tracer. Both are used within the context of a general license from the MPA after a license 
application (Licensmotivering avseende Generell humanlicens) since many years, and this is 
regularly updated. 
8.2 Dose and administration 
In this trial a low dose of Magtrace® 28mg/ml (0.1ml) will be injected intracutaneously at one 
time-point. This is different from the recommendation of 1-2 mL in the subcutaneous tissue. 
The rationale is that the lymphatic outflow from an intracutaneous injection is much higher, 
and a lower dose is then needed. This is the same type of injection that is currently used with 
Tc99 and blue dye. The injection should be done slowly with a thin needle in the most 
superficial part of the skin, so that the tip of the needle is visible and that the Magtrace® 
creates a small spider web in the skin as it enters the lymphatic vessels. 
8.3 Packaging, labelling, and handling of investigational products(s) 
Magtrace® will be purchased by the official distributor in Sweden according to current 
clinical routine and stored according to manufacturer’s instructions. As control, the routine 
use of Tc99 and blue dye will be used according to current clinical routine. Magtrace® will be 
packaged, delivered and stored according to manufacturer’s instructions and current clinical 
routine and accompanied with the approved study IFU.  

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9 SAFETY AND TOLERABILITY 
Safety reporting in clinical investigations of medical devices shall be performed in line with 
the requirements of the Regulation (EU) 2017/745 – Medical Device Regulation (MDR) 
Article 80(2). The sponsor shall report, without delay to all Member States in which the 
clinical investigation is being conducted, all of the following by means of the electronic 
system referred to in MDR Article 73: 
a. any serious adverse event that has a causal relationship with the investigational device, the 
comparator or the investigation procedure or where such causal relationship is reasonably 
possible; 
b. any device deficiency that might have led to a serious adverse event if appropriate action 
had not been taken, intervention had not occurred, or circumstances had been less fortunate; c. 
any new findings in relation to any event referred to in points 1 and 2. 
 
The period for reporting shall take account of the severity of the event. Where necessary to 
ensure timely reporting, the sponsor may submit an initial report that is incomplete followed 
up by a complete report. 
9.1 Investigational device 
The definition of an investigational device is a device that is assessed in a clinical 
investigation, MDR Article 2(46). An investigational device can be a non-CE marked device 
or a CE marked device. The definition does not differentiate between different regulatory 
statuses of devices. However, the reporting requirements are different depending on whether 
the clinical investigation is done for purposes described in Article 62, 74 or 82. The definition 
is understood to cover also the devices investigated in PMCF investigations, even if they are 
not subject to notification per Article 74.2. 
9.1.1 Adverse Event (AE)  
An adverse event is defined as any untoward medical occurrence experienced by or 
worsening of a pre-existing condition of a subject during this trial in relation to the 
investigational device or study procedure. The assessment whether a detected adverse event is 
related to the investigational product or procedure is done by the specific site investigator. 
Any untoward medical occurrence, unintended disease or injury or any untoward clinical 
signs, including an abnormal laboratory finding, in subjects, users or other persons, in the 
context of a clinical investigation, whether or not related to the investigational device. This 
definition includes events that are anticipated as well as unanticipated events, and also 
includes events occurring in the context of a clinical investigation related to the 
investigational device, the comparator or the procedures involved. 
9.1.2 Serious Adverse Event (SAE) 
A serious adverse event (SAE) is any adverse event that led to any of the following: a) death, 
b) serious deterioration in the health of the subject, that resulted in any of the following: i. 
life-threatening illness or injury, ii. permanent impairment of a body structure or a body 
function, iii. hospitalisation or prolongation of patient hospitalisation, iv. medical or surgical 
intervention to prevent life-threatening illness or injury or permanent impairment to a body 
structure or a body function, v. chronic disease, c) foetal distress, foetal death or a congenital 
physical or mental impairment or birth defect. 

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9.1.3 Device deficiency 
Any inadequacy in the identity, quality, durability, reliability, safety or performance of an 
investigational device, including malfunction, use errors or inadequacy in information 
supplied by the manufacturer. 
9.1.4 Unanticipated Serious Adverse Device Effect (USADE) 
An Unanticipated Serious Adverse Device Effect (USADE) is an effect which by its nature, 
incidence, severity or outcome has not been identified in the current risk assessment. 
Procedures associated with the use of a device should be addressed in the risk assessment, 
which makes it possible to determine whether the procedure related SAEs are Unanticipated 
Serious Adverse Device Effect or not. SAEs related to procedures imposed by the clinical 
investigation plan but not with the use of the device should not be considered Serious Adverse 
Device Effects. 
9.1.5 Causality 
The relationship between the use of the medical device (including the medical - surgical 
procedure) and the occurrence of each adverse event shall be assessed and categorized. 
During causality assessment activity, clinical judgement shall be used and the relevant 
documents, such as the Investigator’s Brochure, the Clinical Investigation Plan or the Risk 
Analysis Report shall be consulted, as all the foreseeable serious adverse events and the 
potential risks are listed and assessed there. The presence of confounding factors, such as 
concomitant medication/treatment, the natural history of the underlying disease, other 
concurrent illness or risk factors shall also be considered. The above considerations apply also 
to the serious adverse events occurring in the comparison group. 
For the purpose of harmonizing reports, each SAE will be classified according to four 
different levels of causality: 1. Not related 2. Possible 3. Probable 4. Causal relationship 
The sponsor and the investigators will use the following definitions to assess the relationship 
of the serious adverse event to the investigational device, the comparator or the investigation 
procedure. 
1. Not related: Relationship to the device, comparator or procedures can be excluded when: - 
the event has no temporal relationship with the use of the investigational device, or the 
procedures related to application of the investigational device; - the serious adverse event 
does not follow a known response pattern to the medical device (if the response pattern is 
previously known) and is biologically implausible; - the discontinuation of medical device 
application or the reduction of the level of activation/exposure - when clinically feasible - and 
reintroduction of its use (or increase of the level of activation/exposure), do not impact on the 
serious adverse event; - the event involves a body-site or an organ that cannot be affected by 
the device or procedure; the serious adverse event can be attributed to another cause (e.g. an 
underlying or concurrent illness/ clinical condition, an effect of another device, drug, 
treatment or other risk factors); - the event does not depend on a false result given by the 
investigational device used for diagnosis, when applicable; In order to establish the non-
relatedness, not all the criteria listed above might be met at the same time, depending on the 
type of device/procedures and the serious adverse event. 
2. Possible: The relationship with the use of the investigational device or comparator, or the 
relationship with procedures, is weak but cannot be ruled out completely. Alternative causes 

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are also possible (e.g., an underlying or concurrent illness/ clinical condition or/and an effect 
of another device, drug or treatment). Cases where relatedness cannot be assessed, or no 
information has been obtained should also be classified as possible. 
3. Probable: The relationship with the use of the investigational device or comparator, or the 
relationship with procedures, seems relevant and/or the event cannot be reasonably explained 
by another cause. 
4. Causal relationship: the serious adverse event is associated with the investigational device, 
comparator or with beyond reasonable doubt when: - the event is a known side effect of the 
product category the device belongs to or of similar devices and procedures; - the event has a 
temporal relationship with investigational device use/application or procedures; - the event 
involves a body-site or organ that - the investigational device or procedures are applied to; - 
the investigational device or procedures have an effect on; - the serious adverse event follows 
a known response pattern to the medical device (if the response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious adverse event (when clinically feasible); - other 
possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an effect of 
another device, drug or treatment) have been adequately ruled out; - harm to the subject is due 
to error in use; - the event depends on a false result given by the investigational device used 
for diagnosis, when applicable; 
In order to establish the relatedness, not all the criteria listed above might be met at the same 
time, depending on the type of device/procedures and the serious adverse event. The sponsor 
and the investigators will distinguish between the serious adverse events related to the 
investigational device and those related to the procedures (any procedure specific to the 
clinical investigation). An adverse event can be related both to procedures and the 
investigational device. Complications caused by concomitant treatments not imposed by the 
clinical investigation plan are considered not related. Similarly, several routine diagnostic or 
patient management procedures are applied to patients regardless of the clinical investigation 
plan. If routine procedures are not imposed by the clinical investigation plan, complications 
caused by them are also considered not related. In some particular cases the event may not be 
adequately assessed because information is insufficient or contradictory and/or the data 
cannot be verified or supplemented. The sponsor and the Investigators will make the 
maximum effort to define and categorize the event and avoid these situations. Where an 
investigator assessment is not available and/or the sponsor remains uncertain about 
classifying the serious adverse event, the sponsor should not exclude the relatedness; the 
event should be classified as “possible” and the reporting should not be delayed. Particular 
attention shall be given to the causality evaluation of unanticipated serious adverse events. 
The occurrence of unanticipated events related could suggest that the clinical investigation 
places subjects at increased risk of harm than was to be expected beforehand. 
9.1.6 Reporting 
All reporting will be performed using the MDCG 2020-10/2 Clinical Investigation Summary 
Safety Report Form v1.0 as provided by the MPA. It shall be transmitted to all NCAs where 
the clinical investigation is being performed. Once Eudamed is available and fully functional 
the obligations and requirements that relate to performing safety reporting via Eudamed shall 
apply from the date corresponding to six months after the date of publication of the notice 

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referred to in Article 34(3) of the MDR. Any reported events will also be sent to Endomag for 
their knowledge. 
Contact details to sponsor: Professor Fredrik Wärnberg, Dept. of Surgery, Sahlgrenska 
University Hospital 413 45 Gothenburg Sweden Fax: +46 31-823931 Phone: +46 70 6146251 
E-mail: fredrik.warnberg@vgregion.se 
Reportable events: For the purpose of this guidance and based on the definitions above, the 
following events are considered reportable events in accordance with MDR Art. 80(2): 
1. any serious adverse event that has a causal relationship with the investigational device, the 
comparator or the investigation procedure or where such causal relationship is reasonably 
possible; 
2. any device deficiency that might have led to a serious adverse event if appropriate action 
had not been taken, intervention had not occurred, or circumstances had been less fortunate; 
3. any new findings in relation to any event referred to in points 1 and 2. 
Reporting timelines: Reportable events have to be reported to the sponsor immediately, but 
not later than 3 calendar days after investigation site study personnel’s awareness of the event. 
Reportable events have to be reported to the competent authority by the sponsor of the clinical 
investigation. The timeline for these reports is based on: 
1. For all reportable events which indicate an imminent risk of death, serious injury, or serious 
illness and that requires prompt remedial action for other patients/subjects, users or other 
persons or a new finding to it: Immediately, but not later than 2 calendar days after awareness 
by sponsor of a new reportable event or of new information in relation with an already 
reported event. This includes events that are of significant and unexpected nature such that 
they become alarming as a potential public health hazard. It also includes the possibility of 
multiple deaths occurring at short intervals. These concerns may be identified by either the 
NCA or the manufacturer. 
2. Any other reportable events or a new finding/update to it: Immediately, but not later than 7 
calendar days following the date of awareness by the sponsor of the new reportable event or 
of new information in relation with an already reported event 
10 TERMINATION OF THE CLINICAL STUDY 
The study end is defined as date of the last visit of the last subject participating in the study. 
11 STATISTICS  
11.1 Statistical methods 
We estimate the SLN detection rate to be about 98% for both Magtrace® and the dual 
technique based on our earlier feasibility study where all patients had a successful SLN-
biopsy with 0.1ml Magtrace® intracutanously. The detection rate for the dual technique is 
estimated based on our earlier studies, i.e., Nordic Trial, Monos and SentiDose trials. We set 
an acceptable difference in SLN-detection rate to 4%. If there is truly no difference between 
the dual technique and the experimental 0.1ml Magtrace®, then 386 patients would be 

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required in a randomised study to be 80% sure that the upper limit of a one sided 97.5% 
confidence interval will exclude a difference in favour of the dual technique of more than 4%. 
As every patient is their own control the sample size required is 193. Allowing for a dropout 
rate of approximately 10%, 220 patients will be recruited.  
 
For the second endpoint skin staining, a subgroup of patients will be included in the analyses. 
Regarding skin staining, only patients undergoing breast conserving surgery will be included. 
As breast conserving surgery is done in approximately 85% of all patients, this cohort will 
include approximately 187 patients. 
 
For the second endpoint, MRI artefacts, 50 of the 187 patients undergoing breast conserving 
surgery will be asked separately if they accept doing an MRI at 3-6, 12 and 24-36 months 
postoperatively. These patients will only be included in Gothenburg and Uppsala. They are 
recruited consecutively, and inclusion stops when 50 have accepted participation. 
11.2 Drop-outs 
Persons that drop-out from the study can be replaced.  
12 OPERATIONAL AND ADMINISTRATIVE 
CONSIDERATIONS 
12.1 Procedure for clinical study quality control 
This trial will be conducted in accordance with the GCP standard ISO 14155, Clinical 
investigations of medical devices for human subjects – Good clinical practice, version SS-EN 
ISO 14155:2020)  
12.1.1 Data Collection 
All data on each subject generated according to the protocol must be recorded continuously in 
the CRF. 
12.1.2 Data Management 
Data management will be coordinated by the sponsor. 
12.1.3 Specification of Source Documents 
The investigator must keep source documents for each subject in the study. A document 
describing what has been classified as source data in the study should be included in the 
Investigator Site File (ISF). The investigator must ensure that all source documents are 
accessible for monitoring and other quality control activities. 
 
The following documents are considered source, including but not limited to: Medical 
records, medical records from other department(s), or other hospital(s), or discharge letters 
and correspondence with other departments/hospitals, if subject visited any during the study 
period. 
Source data must be available at the centre to document the existence of the study subjects 
and substantiate the integrity of study data collected. The following information (at least but 
not limited to) should be included in the source medical records: 
1. Demographic data (age, sex, weight, and height) 

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2. Participation in the study and signed and dated Informed Consent Form 
3. Visit dates 
4. Key efficacy and safety data (as specified in the protocol) 
5. Reason for premature discontinuation 
12.1.4 Direct Access to Source Data/Documents 
The investigator and the study site must accept auditing by the sponsor as well as inspections 
from the Independent Ethics Committee (IEC) and relevant regulatory authorities. The 
confidentiality of the subjects’ identities shall be well protected consistent with local and 
national regulations when the source documents are subject to direct access. 
12.1.5 Data storage and management 
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. All source data including informed consent, a copy of 
completed CRF if applicable, original protocol with amendments and the final report will be 
stored at study site for a minimum period of 15 years after termination of the trial, in 
accordance with Swedish regulation/law (Chapter 10, 3 § in LVFS 2011:19). 
 
Staff designated by the Sponsor will review the data entered into the eCRFs by investigational 
staff for completeness and accuracy and instruct the site personnel to make any required 
corrections or additions. Queries are issued electronically. Designated investigator site staff is 
required to respond to the query and confirm or correct the data. 
 
At the conclusion of the study, the occurrence of any protocol deviations will be determined. 
After these actions have been completed and the database has been declared to be complete 
and accurate, it will be locked and available for data analysis. 
12.2 Clinical Study Monitoring  
A study monitor will be appointed by the sponsor. The monitor will be appropriately trained 
and informed about the nature of the study, subject written information, GCP and applicable 
regulatory requirements. The monitor’s qualifications will be documented. 
 
The monitor will have regular contacts with the clinic to verify informed consents of 
participating subjects, to confirm that facilities remain acceptable, that the investigational 
team is adhering to the protocol, that data are being accurately recorded in the CRFs, to verify 
inclusion/exclusion criteria, study main endpoints, check AE/SAE reporting and that product 
accountability is being carried out. The investigator should ensure that all persons assisting 
with the trial are adequately informed and trained about the protocol, the investigational 
products(s) and their trial related duties and factions. The monitor will check that training has 
been performed and that this is documented. The monitor will also ensure source data 
verification (comparison of the data in the eCRF with the medical records and other source 
data). The monitor must have direct access to source data. The confidentiality of the subjects’ 
identities shall be well protected consistent with local and national regulations when the 
source documents are subject to direct access. The extent of monitoring will be defined in a 
monitoring plan. 

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12.3 Audits and inspections 
Authorized representatives of the sponsor, a Competent Authority or an Ethics Committee 
may perform audits or inspection at the center, including source data verification. The 
purpose of an audit or inspection is to examine all study-related activities and documents 
systematically and independently, to determine whether these activities were conducted, and 
data were recorded, analysed and accurately reported according to the protocol, Good Clinical 
Practice (GCP) and any applicable regulatory requirements. The monitor(s), the auditor(s), 
and the MPA(s) must be granted direct access to the subject’s original medical records for 
verification of clinical trial procedures and/or data, without violating the confidentiality of the 
subject, to the extent permitted by the applicable laws and regulations. 
 
12.4 Deviations from clinical investigation plan 
An Investigator must not make any changes or deviate from the protocol, except to protect the 
life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor, the reviewing ethics committee and the MPA of any deviation from the 
investigational plan to protect the life or physical well-being of a subject in an emergency, 
and those deviations which affect the scientific integrity of the clinical investigation. Such 
notice shall be given as soon as possible, but no later than 3 business days after the emergency 
occurred. All deviations from the investigational plan will be reported to the sponsor. 
Investigators must also adhere to ethics committee and MPA reporting requirements for 
institutional reporting of deviations. Deviations will be reviewed throughout the study. If 
necessary, corrective and preventive actions will be initiated by the sponsor. Principal 
investigator disqualification will be initiated if a principal investigator repeatedly or 
deliberately deviates from the protocol for reasons other than to protect the rights, safety and 
well-being of human subjects under emergency circumstances, if the investigator repeatedly 
or deliberately submits false information to the sponsor, ethics committee or, if applicable, 
MPA 
12.5 Ethics and protection of subject confidentiality 
12.5.1 Independent Ethics Committee  
This protocol and the Subject Information Sheet and Informed Consent Form will be 
submitted to both the Swedish Ethical Review Authority and the Swedish Medical Products 
Agency according to the national laws and regulations. Prior to starting the study favourable 
opinion must be obtained in writing. No subject must be included in the study before the 
accredited Ethics Committee and the MPA has issued a favourable opinion. 
 
12.5.2 Protocol Amendment and/or Revision 
Any changes to the study, which arise after approval of the protocol, must be documented as 
protocol amendment or administrative amendments. Depending on the nature of the 
amendment and/or revision, either approval from the accredited Ethics Committee and the 
MPA or notification is required. The changes will become effective only after the approval of 
the sponsor, the regulatory authority and the accredited Ethics Committee and the MPA (if 
applicable). Written verification of the accredited Ethics Committee and the MPA and 
regulatory authority approval will be obtained before any amendment is implemented. 

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12.5.3 Ethical Conduct of Study 
The investigator(s) and all parties involved in this study should conduct the study in 
adherence to the ethical principles based on the Declaration of Helsinki, Good Clinical 
Practice (GCP), ICH Guidelines (GCP standard ISO 14155, Clinical investigations of medical 
devices for human subjects – Good clinical practice, version SS-EN ISO 14155:2020). 
12.5.4 Informed Consent of Subjects 
The Principal Investigator at each centre will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose and possible risks and benefits of the 
study. Subjects must also be notified that they are free to discontinue from the study at any 
time. The subject should be given the opportunity to ask questions and allowed time to 
consider the information provided. 
 
Verbal and written informed consent must take place before any specific procedure related to 
the study is started. Signed and dated informed consent will be obtained from each patient in 
accordance with the principles of Good Clinical Practice (GCP). Documentation that the 
informed consent was signed and dated prior to study inclusion must be entered into the 
medical records at the time the informed consent is obtained. The original, signed Informed 
Consent Form (ICF) must be stored in the Investigator’s Study File. A copy of the signed ICF 
must be given to the subject. 
12.5.5 Subject Confidentiality 
All patient data collected and processed for the purposes of this study will be managed by the 
sponsor with adequate precautions to ensure the confidentiality of those data, and in 
accordance with applicable national and/local laws and regulations on personal data 
protection. No patient identifiable data will be obtained. In any presentations of the results of 
this study; at meetings or in publications, the patients’ identity will remain confidential. 
12.6 Administrative matters 
The sponsor will be responsible for all data registrations, statistical programming and analysis 
as well as statistical quality control and validation of programming and statistical analysis. 
The sponsor will be responsible for the collected data in the study. 
12.6.1 Arrangement for Use of Information and Publication of the Clinical Study 
The study will be registered on clinicaltrials.gov, the results from the trial will be presented at 
scientific symposia and congresses, and in a peer reviewed scientific journal. Authorship 
credit should be based on substantial contribution to conception and design, execution, or 
analysis and interpretation of data. All authors should be involved in drafting the article or 
revising it critically for important intellectual content and must have read and approved the 
final version of the manuscript. Authors should adhere to the practices of their research field 
and the guidelines of the International Committee of Medical Journal Editors (ICMJE) 
12.6.2 Documents and Records Related to the Clinical Study 
The investigator will archive all study data (e.g., Subject Identification Code List, source data, 
CRFs, and Investigator's File) and relevant correspondence. These documents are to be kept 
on file for at least 15 years after final study report, in case of audit or follow-up of subjects 
who participated in the study. The investigator agrees to obtain the sponsor’s agreement prior 
to disposal, moving, or transferring of any study-related records. The sponsor will archive and 
retain all documents pertaining to the study according to local regulations. 

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12.7  Economics 
There will be no financial compensation for study participants. Sponsoring of the trial from 
Endomagnetics Limited will be given as an institutional grant to cover costs for the research 
procedures involved in the trial. 
12.8 Publications 
After completion of the study, the results will be analysed, and a clinical study report will be 
prepared. Within one year after the end of the study, the sponsor will submit a final study 
report with the results of the study, including any publications/abstracts of the study, to the 
accredited Ethics Committee and the MPA. 
The study results will be considered for publication in an international peer-reviewed journal 
and/or presented at scientific symposia and congresses. Both positive and negative results will 
be published. 
12.9  Insurance 
The study subjects are covered by the Swedish Patient Insurance. 
13 STUDY ORGANIZATION 
The study is conducted at Department of Surgery, Sahlgrenska University Hospital. Screening 
and enrolment of patients will be done from patients being referred for SLNB at the different 
study sites.  
14 REFERENCES 
1. Balch, C.M., Detection of melanoma metastases with the sentinel node biopsy: the legacy 
of Donald L. Morton, MD (1934-2014). Clin Exp Metastasis, 2018. 35(5-6): p. 425-429. 
2. Waanders, S., et al., A handheld SPIO-based sentinel lymph node mapping device using 
differential magnetometry. Phys Med Biol, 2016. 61(22): p. 8120-8134. 
3. Karakatsanis, A., et al., Superparamagnetic iron oxide nanoparticles as the sole method 
for sentinel node biopsy detection in patients with breast cancer. Br J Surg, 2017. 
4. Karakatsanis, A., et al., The Nordic SentiMag trial: a comparison of super paramagnetic 
iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel 
node (SN) in patients with breast cancer and a meta-analysis of earlier studies. Breast 
Cancer Res Treat, 2016. 157(2): p. 281-294. 
5. Mirzaei N, Katsarelias D, Zaar P, Jalnefjord O, Johansson I, Leonhardt H, Wärnberg F, 
Olofsson Bagge R. Sentinel lymph node localization and staging with a low-dose of 
superparamagnetic iron oxide (SPIO) enhanced MRI and magnetometer in patients with 
cutaneous melanoma of the extremity - The MAGMEN feasibility study. Eur J Surg 
Oncol. 2022 Jan 1;S0748-7983(21)01439-6. 
 

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6.   Andreas Karakatsanis, Kosmas Daskalakis, Peter Stålberg, Helena Olofsson, Yvette    
Andersson, Staffan Eriksson, Leif Bergkvist, Fredrik Wärnberg. The routine use of Super 
Paramagnetic Iron Oxide nanoparticles as the sole method for Sentinel Node Biopsy in 
patients with breast cancer. The MONOS study. Br J Surg. 2017 Nov;104(12):1675-1685.  
 
 
7.   Hersi AF, Pistiolis L, Dussan Luberth C, Vikhe-Patil E, Nilsson F, Mohammed I, 
Olofsson Bagge R, Wärnberg F, Eriksson S, Karakatsanis A. Optimizing Dose and Timing 
in Magnetic Tracer Techniques for Sentinel Lymph Node Detection in Early Breast 
Cancers: The Prospective Multicenter SentiDose Trial. Cancers (Basel). 2021 Feb 
9;13(4):693.  
 
8. Balkrishnan R, Kelly AP, McMichael A, Torok H. Improved quality of life with 
effective treatment of facial melasma: the pigment trial. J Drugs Dermatol 2004; 3(4):  
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