Determining the Magnitude of Early Steps of Fatty Acid Oxidation in Cerebral Metastases Using [18F]FPIA PET/MRI
Conditions: Cerebral Metastases
Sponsor: Imperial College London

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Determining the magnitude of early steps of fatty acid oxidation in cerebral 
metastases using [18F]FPIA PET/MRI 
Short title: Measuring fatty acid oxidation in cerebral metastases using [18F]FPIA  
 
Chief Investigator:    
Dr. Matthew Williams1  
Principal Investigator:     Prof. Eric Aboagye2                            
Co- Investigators:     
Prof. Adam Waldman1,3, Dr. Shahriar Islam4, 
Dr. Matthew Grech-Sollars2, Dr. Tara Barwick1,  
Dr. Suraiya Dubash2, Ms. Kasia Kozlowski2, Dr. 
Frans Van Den Berg5, Mr. David Peterson1,  
Mr. Kevin O’Neil1, Dr. Clara Limback1, Ms. Sophie 
Camp1, Mr. Giulio Anchini1, Dr. Anastassia 
Gontsarova1, Dr Neva Patel1 
1 Imperial College Healthcare NHS Trust. 
2 Department of Surgery and Cancer, Imperial College 
London. 
3Centre for Clinical Brain Sciences, University of      
Edinburgh. 
4 Faculty of Medicine, Imperial College London 
5  Invicro, Centre for Imaging Sciences. 
 
Sponsor: 
 
 
Imperial College London 
Funder:        
 
Medical Research Council  
Protocol Version :            2.0 
 
Protocol Date:    
 
08Apr2022 
 
IRAS Project ID: 272728  
REC reference: 20/SC/0134 
 

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CONTACT LIST 
 
Chief Investigator 
Dr Matthew Williams 
Radiotherapy Department 
Charing Cross Hospital 
Fulham Palace Road 
London, W6 8RF 
Tel: 020 3311 0733                                 
 
 
Principal Investigator 
Professor Eric Aboagye 
 
Professor of Cancer Pharmacology & Molecular Imaging,  
Imperial College London 
Commonwealth Building GN1  
Hammersmith Campus 
Du Cane Road 
London, W12 0NN 
 
 
Study Co-ordination Centre: 
Comprehensive Cancer Imaging Centre Office 
Imperial College London 
Commonwealth Building GN1  
Hammersmith Campus 
Du Cane Road 
London, W12 0NN 
Tel: 020 3313 3720  
 
 
 
 
 
 
 

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Sponsor: 
 
 
Funder: 
 
 
This protocol describes the ‘Determining the magnitude of early steps of fatty 
acid oxidation in cerebral metastases using 18F-FPIA PET/MRI’ study and 
provides information about procedures for entering participants. Every care was 
taken in its drafting, but corrections or amendments may be necessary. These 
will be circulated to investigators in the study. Problems relating to this study 
should be referred, in the first instance, to the Chief Investigator. This study will 
adhere to the principles outlined in the UK Policy Frame Work for Health and 
Social Care Research. It will be conducted in compliance with the protocol, the 
Data Protection Act and other regulatory requirements as appropriate. 
Clinical Queries: Clinical queries should be directed to Dr Matthew Williams who 
will direct the query to the appropriate person 
 
 
 
Imperial College London is the main research Sponsor for this study.  
For further information regarding the sponsorship conditions, please contact the Head of 
Regulatory Compliance at:  
Research Governance and Integrity Team (RGIT) 
Imperial College London and Imperial College Healthcare NHS Trust  
Room 215, Level 2, Medical School Building  
Norfolk Place  
London, W2 1PG  
Tel: 020 7594 9459/ 020 7594 1862  
https://www.imperial.ac.uk/research-and-innovation/research-office/research-governance-and-
integrity/  
Medical Research Council 
One Kemble Street London, WC2B 4AN 

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Investigator Protocol Agreement Page 
 
 
• 
I confirm agreement to conduct the study in compliance with the protocol. 
• 
I acknowledge that I am responsible for overall study conduct. 
• 
I agree to personally conduct or supervise the described clinical study in 
accordance with Good Clinical Practice requirements. 
• 
I agree to ensure that all associates, colleagues and employees assisting 
in the conduct of the study are informed about their obligations.  
• 
I authorise this protocol. 
 
 
Chief Investigator Name: 
Dr. Matthew Williams 
 
Investigator Address: 
Radiotherapy Department 
Charing Cross Hospital 
Fulham Palace Road 
London W6 8RF 
United Kingdom 
 
 
T: 020 3311 0733                                 
 
 
Investigator Signature 
 
Date 
 
 
 
 

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TABLE OF CONTENTS 
1       LIST OF ABBREVIATIONS and TERMS .................................................................... 7 
2       SYNOPSIS ............................................................................................................ 8 
3       BACKGROUND AND RATIONALE ........................................................................ 10 
3.1   Background .............................................................................................................. 10 
3.2   Rationale .................................................................................................................. 11 
3.2.1 Aim ............................................................................................................................. 11 
3.2.2 Hypothesis ................................................................................................................. 11 
4        STUDY OBJECTIVES AND ENDPOINTS ................................................................ 12 
4.1  
Study Objectives .................................................................................................. 12 
4.1.1 
Primary Objective: ................................................................................................. 12 
4.1.2 
Secondary Objectives: ......................................................................................... 12 
4.1.3 
Tertiary Objective: ................................................................................................. 12 
4.2 
Study Endpoints ................................................................................................... 12 
4.2.1    Primary Endpoint: ................................................................................................. 12 
4.2.2 
Secondary Endpoints: .......................................................................................... 12 
4.2.3   Tertiary Endpoint: ................................................................................................... 12 
5        STUDY OUTLINE ................................................................................................ 13 
5.1   Study Overview ........................................................................................................ 13 
5.2  Study Flow Chart ....................................................................................................... 13 
6       PARTICIPANT ENTRY .......................................................................................... 14 
6.1  Identification and recruitment of subjects .................................................................. 14 
6.2  Screening .................................................................................................................. 15 
6.3  Inclusion Criteria ....................................................................................................... 15 
6.4  Exclusion Criteria ....................................................................................................... 16 
6.5  ID Assignment ........................................................................................................... 16 
7       STUDY PROCEDURES ......................................................................................... 17 
7.1  Schedule of Events ..................................................................................................... 17 
Table 1. ............................................................................................................................ 17 
7.2  Screening Period ........................................................................................................ 18 
7.3  Screening Assessments .............................................................................................. 18 
7.3.1  Demographic Data and Medical History .............................................................. 18 
7.3.2  WHO Performance Status ..................................................................................... 18 
Table 2: ..................................................................................................................... 18 
7.3.3 
Pregnancy Test ..................................................................................................... 18 
7.3.4   Laboratory Evaluations ......................................................................................... 19 
7.3.5   Concomitant Medications ..................................................................................... 19 
7.3.6   Vital Signs ............................................................................................................... 19 
7.3.7   Follow Up period .................................................................................................... 19 
8       COMPLETION, WITHDRAWAL AND TERMINATION CRITERIA .............................. 19 
8.1 
Completion .......................................................................................................... 19 
8.1.1   Definition of completed subject ............................................................................ 19 

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8.1.2   Definition of an evaluable subject ........................................................................ 19 
8.1.3   Time on study ......................................................................................................... 20 
8.2  Rules for subject withdrawal ...................................................................................... 20 
8.3  Rules for terminating study ........................................................................................ 20 
8.4  End of Study .............................................................................................................. 21 
9       RADIOTRACER AND IMAGING ............................................................................ 21 
9.1  Radiopharmaceutical ................................................................................................. 21 
9.2  Imaging Protocol ....................................................................................................... 22 
9.3  PET Protocol .............................................................................................................. 22 
9.4  MRI Protocol ............................................................................................................. 22 
9.5  Radiation dosimetry .................................................................................................. 23 
Table 3: Radiation dose estimation ........................................................................... 23 
9.6  Radiation dose .......................................................................................................... 23 
9.7  Imaging Complications ............................................................................................... 24 
10 ADVERSE EVENTS .............................................................................................. 25 
10.1  Definitions ............................................................................................................... 25 
10.2  Reporting of Adverse Events .................................................................................... 26 
10.2.1 Non serious AEs .................................................................................................... 26 
10.2.2 Serious AEs ............................................................................................................ 26 
11       STATISTICS AND DATA ANALYSES .................................................................... 27 
11.1  Statistical Design ..................................................................................................... 27 
11.2  PET Analysis ............................................................................................................ 27 
11.3  Kinetic Analysis ........................................................................................................ 27 
11.4  MRI Analysis ............................................................................................................ 28 
12       REGULATORY, ETHICAL AND LEGAL ISSUES ...................................................... 28 
12.1  Good Clinical Practice .............................................................................................. 28 
12.2  Ethics Approval ........................................................................................................ 28 
12.3  Approval of Amendments ........................................................................................ 29 
12.4  ARSAC Approval ...................................................................................................... 29 
12.5  Informed Consent .................................................................................................... 29 
12.6  Indemnity ................................................................................................................ 30 
12.7  Sponsor ................................................................................................................... 30 
12.8  Funding ................................................................................................................... 30 
12.9  Subject Confidentiality ............................................................................................. 30 
12.10  Material Storage and Analysis. ............................................................................... 31 
13       DATA MANAGEMENT ...................................................................................... 32 
13.1  Data Recording and Storage ..................................................................................... 32 
13.2  Audits and inspections ............................................................................................. 32 
13.3  Disclosure of Data .................................................................................................... 33 
14       STUDY MANAGEMENT .................................................................................... 33 
15       PUBLICATION AND DISSEMINATION ................................................................ 33 
16       REFERENCES .................................................................................................... 34 

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1       LIST OF ABBREVIATIONS and TERMS                                                                                  
 
AE 
 
 
Adverse event 
 
 
ARSAC  
 Administration of Radioactive Substances Advisory       
Committee 
CT 
 Computed Tomography 
ED 
 Effective Dose (i.e., the sum of risk weighted organ absorbed     
radiation dose used as a measure of stochastic radiation 
risk) 
EC 
 Ethics committee 
FDG 
  18F – fluorodeoxyglucose 
18F  
 
 
Fluorine with an Atomic Mass of 18 
[18F]FPIA 
 
18F-fluoropivalate (18F-fluoro-2,2-dimethylpropionic acid) 
GCP  
 
Good Clinical Practice 
GMP 
 
 
Good Manufacturing Practice 
i.v  
 
 
Intravenous 
MBq     
 
Megabecquerel 
PET 
 Positron emission tomography 
SAE   
 
Serious adverse event 
SRS   
 
Stereotactic radiosurgery 
SUV  
 
Standardized uptake value 
MRI 
 
 
Magnetic resonance imaging 
eGFR  
 
Estimated glomerular filtration rate 
 
 
 
 
 
 
 
 
 

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2       SYNOPSIS 
Name of Sponsor: Imperial College London 
Name of biomarker: [18F]Fluoropivalate positron emission tomography magnetic 
resonance imaging (18F-FPIA PET/MRI) 
Title of Study:  Determining the magnitude of early steps of fatty acid oxidation in 
cerebral metastases using [18F]FPIA PET/MRI 
Study Centres:    
• Invicro, Hammersmith Hospital Campus, UK  
• Imperial College London   
• Imperial College Healthcare NHS Trust, London  
Phase of Development: Explorative biomarker use/ Phase 2 
 
Primary Objective:  
• Determine the magnitude of the early steps of fatty acid oxidation in cerebral 
metastases using [18F]FPIA PET/MRI. 
 
Secondary objective: 
• Investigate the magnitude of tracer-derived biochemical uptake between 
treated metastases and treatment naïve metastases. 
 
Tertiary objective: 
• Comparison of tracer-derived biochemical uptake measure with conventional 
MRI variables including perfusion imaging and contrast enhancement. 
 Primary Endpoint:  
• Quantitative measurement of [18F]FPIA uptake in cerebral metastases. 
 
Secondary endpoint: 
• Distribution of [18F]FPIA uptake in lesions which have undergone treatment, 
with those that are treatment naïve. 
 
Tertiary endpoint: 
• Correlation of [18F]FPIA variables with volumetric and functional MRI 
variables including perfusion.  
 
Selection of Subjects: Inclusion Criteria: 
Patients with radiological evidence of cerebral metastases on MRI  that are either: 

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A) Treatment naïve*  
or 
B) SRS +/- combination treated** 
and 
C)  that fulfill the following criteria: 
 
1. Age ≥18 
2. Target metastases size ≥ 1cm.    
3. WHO performance status 0 – 2. 
4. If female, the subject is either post-menopausal (at least 1 year), or surgically 
sterilized (has had a documented bilateral oophorectomy and/or documented 
hysterectomy for at least 2 years), or if of childbearing potential, must have a 
negative urine beta human chorionic gonadotropin (β-HCG) pregnancy test done  
prior to tracer administration.   
5. The subject is able and willing to comply with study procedures, and a signed 
and dated informed consent is obtained. 
6. The subject has a satisfactory medical history as judged by the investigator with 
no significant co-morbidities.  
7. The subject’s clinical and laboratory tests are within normal limits and/or 
considered clinically insignificant. 
 
* Treatment Naïve = =  patients who have not and will not be undergoing treatment 
for  cerebral metastases at the time of the PET/MRI scan. 
 ** SRS+/- combination therapy = patients who have completed the stereotactic 
radiosurgery (SRS)  part of  a combination regime   enabling a 4-8 week post SRS 
treatment 
PET/MRI 
scan. 
 
Combination 
therapy 
can 
be 
+/- 
chemotherapy/immunotherapy/targeted therapies. 
 
Exclusion Criteria: 
1.  The subject is pregnant or lactating. 
2.  Any other chronic illness that will or musculoskeletal condition that would not 
allow comfortable performance of a PET study. 
3.  Prior use within 14 days of enrolment or concurrent therapy with any other 
investigational agent. 
4.  Unsatisfactory renal function (eGFR<30). 

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3       BACKGROUND AND RATIONALE  
3.1   Background 
Cerebral metastases represent a significant problem for oncological management. 
It is estimated that 20% to 40% of patients with cancer will develop metastatic 
cancer to the brain during the course of their illness [1]. The burden 
of brain metastases impacts on quality and length of survival. Although 
cerebral metastases may spread from any primary site, most common primary site 
is the lung, followed by the breast then gastrointestinal sites.   Very recent work 
indicates a striking common metabolic phenotype of brain metastases and 
glioblastoma  to simultaneously oxidise acetate and glucose [3].  This adaptation 
may be important for meeting the high biosynthetic and bioenergetic demands of 
malignant growth. Furthermore, it has been shown that the key gene responsible 
5.  The subject has non-MRI compatible devices (e.g. a pacemaker, an 
implantable cardioverter-defibrillator (ICD), a nerve stimulator, a cochlear 
implant or a drug pump) or implanted material (e.g. non-MRI compatible 
sternal wires, biostimulators, metals or alloys).  
Number of Patients Planned: 24 
• In the event of  withdrawals or unevaluable data, additional patients will be 
recruited to reach a total number of 24 evaluable subjects. 
 
Treatment of Subjects: Experimental imaging biomarker tracer:   
• Subjects will receive a single I.V. bolus injection of [18F]FPIA over a period 
of about 30 seconds.  The tracer injection will be followed by a saline flush.  
Patients will receive a maximum 18F activity of 370 MBq per scan, and a 
maximum of 2 scans.  
Statistical Methods and Planned Analysis:  
• The study is an Observational Non-randomised Phase 2 study to determine 
the magnitude of the early steps of fatty acid oxidation in cerebral metastases 
using [18F]FPIA PET/MRI. This is the first time we are using FPIA in patients 
with cerebral metastases, thus we do not know a priori the magnitude of 
uptake.  Statistical tests will use a 0.05 significance level and will be 2-sided 
unless otherwise noted. 24 evaluable patients will be recruited for the study 
with the Upper Confidence Interval of sensitivity to detect fatty acid 
metabolism set to ≥ 90%.  
 

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for this phenotype, ACSS2, permits cells to exist under bioenergetic stress, which 
is a potential adaptation to therapy resistance [4]. Tumour cells, including brain 
tumour cells efficiently oxidize fatty acids synthesized from acetate to generate a 
substantial part of the cell’s ATP requirement, as well as NADPH to buffer reactive 
oxygen species.  
There is currently no method for quantifying tissue fatty acid oxidation in humans. 
Our group has characterized 18F-fluoropivalate ([18F]FPIA; 3-18F-fluoro-2,2-
dimethylpropionic acid) as a tracer to report the early steps of fatty acid oxidation 
in non-clinical studies using PET imaging [4] [5]. 18F-FPIA shows high contrast for 
imaging brain tumour xenografts implanted subcutaneously in mice [5], and 
orthotopically in the brain (unpublished) with the magnitude of tumour uptake 
equivalent to that of conventional tracers such as [18F]FDG but with significantly 
lower normal brain uptake giving a high signal to noise ratio enabling its use as 
suitable surrogate biomarker for fatty acid oxidation.  Our current objective is to 
quantify the magnitude of early step fatty acid oxidation in cerebral metastases 
thought to possess enhanced fatty acid oxidation [3].   
Combined hybrid PET/MRI technology permits simultaneous acquisition of PET 
imaging with conventional MRI sequences including T1, T2/FLAIR (with and 
without contrast) and perfusion (DSC-MRI).  Patients with brain metastases will 
either be treatment naïve or have undergone radiotherapy and so we will have the 
opportunity to investigate the degree of fatty acid oxidation between untreated and 
treated patient groups, as well as differences in fatty acid metabolism between 
cerebral metastases from different primary tumours. Depending on the outcome of 
this study, [18F]FPIA PET/MRI may be further investigated, in a longitudinal setting, 
for assessing response to therapies including intracranial stereotactic radiosurgery 
in patients with brain metastases. 
3.2   Rationale 
3.2.1 Aim 
The aim of this study is to quantify the degree of early step fatty acid 
oxidation in cerebral metastases as imaged by [18F]FPIA PET/MRI. 
3.2.2 Hypothesis 
We hypothesise that FPIA uptake will be higher in metastases that are 
treatment naïve compared to those that have undergone treatment, in 
keeping with viable tumour cells having a high propensity to generate ATP 
and NADPH via fatty acid oxidation under bioenergetic stress. 

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4        STUDY OBJECTIVES AND ENDPOINTS  
 
4.1  
Study Objectives 
4.1.1 Primary Objective:   
• Determine the magnitude of the early steps of fatty acid oxidation in cerebral 
metastases using [18F]FPIA PET/MRI. 
4.1.2 Secondary Objectives: 
• Investigate of the magnitude of tracer-derived biochemical uptake between 
treated metastases and treatment naïve metastases. 
4.1.3 Tertiary Objective: 
• Comparison 
of 
tracer-derived 
biochemical 
uptake 
measure 
with 
conventional MRI variables including perfusion imaging and contrast 
enhancement. 
 
4.2 
Study Endpoints 
4.2.1    Primary Endpoint:  
• Quantitative measurement of [18F]FPIA uptake in cerebral metastases. 
 
4.2.2 Secondary Endpoints: 
• Distribution of [18F]FPIA uptake in lesions which have undergone treatment, 
with those that are treatment naïve. 
   
4.2.3   Tertiary Endpoint: 
• Correlation of [18F]FPIA variables with volumetric and functional MRI 
variables including perfusion.  
 
 
 
 

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5        STUDY OUTLINE 
 
5.1   Study Overview 
24 evaluable patients with radiological evidence of cerebral metastases on MRI 
will be enrolled into the study (12 who are treatment naïve + 12 who have 
completed SRS+/- combination therapy).  The patients invited to participate in the 
study will provide written informed consent, but will only undergo [18F]FPIA 
PET/MRI imaging once they have satisfied the inclusion and exclusion criteria.. 
Once these have been satisfied, eligible patients will proceed to [18F]FPIA 
PET/MRI. The same treatment naiive patients, who have had one [18F]FPIA 
PET/MRI scan and completed SRS+/- combination therapy, may be invited to take 
part in a second [18F]FPIA PET/MRI scan, as long as they satisfy the inclusion and 
exlusion criteria. 
On the day of imaging the patients will undergo a blood test to measure plasma 
concentrations of carnitine (approximately 6mls).   During the scan, a single dose 
of [18F]FPIA (maximum, 370 MBq) IV will be administered to the participant 
followed by a whole brain dynamic PET/MRI scan over 66 minutes.  During the 
MRI sequences, the patient will receive a 2 stage IV bolus of Gadolinium contrast 
medium administered through a peripheral venous cannula.   
 
5.2  Study Flow Chart 
 
Figure 1.      
 
 
 
 
 
 
 

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6       PARTICIPANT ENTRY 
A target of 24 evaluable subjects will be recruited.  In the case of subject withdrawal 
or non-evaluable subjects before or after dosing,  additional subjects will be 
enrolled to reach 24 evaluable subjects.  
6.1  Identification and recruitment of subjects 
Potentially eligible patients will be identified from the Imperial College Healthcare 
NHS Trust oncology multidisciplinary team meeting and from outpatient clinics by 
a members of the clinical and research team. The treating clinician will discuss the 
study with the patient at their clinic appointment and a patient information sheet 
explaining the study will be given to them or agreed to email or post to them either 
by the clinician or by a member of the clinical research team.  Patients will be given 
a minimum of 24 hrs to consider participation in the study. After this time, they will 
be contacted by a member of the research team to discuss the study in more detail. 
Patients will then be invited to attend a screening up to 21 days before tracer 
administration and imaging.  
Figure 2. Recruitment pathway 
 
 
 
 
 
 
 
 
 
 
 
*Treatment naïve or **SRS +/- combination therapy 
 
SRS 
Treated**   
subject 
identified at 
MDT /Clinic 
Subject 
approached 
for study and 
PIS given 
≥  24 hours  
Subject 
contacted 
by the study 
team 
Patient declines study 
Patient agrees to study 
entry 
Proceed to screening visit 
for informed consent and 
schedule imaging  
Treatment 
Naïve * 
subject 
identified at 
MDT /Clinic 

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6.2  Screening 
Each patient will undergo screening assessments to confirm eligibility. Evaluations 
of the tumour and other clinical data obtained as standard of care prior to consent 
may be used for the study, provided they comply with the protocol specified 
timelines. Written informed consent will be obtained before the patient undergoes 
any study specific procedures.  
Each potential patient will be assigned a unique identifier number for use during 
the trial. A complete record of all patients who enter screening for the study, as 
well as those who go on to be enrolled must be maintained at each site.  
6.3  Inclusion Criteria 
 
Patients who meet any of the following inclusion criteria will be considered eligible 
for this study: 
 
Patients with radiological evidence of cerebral metastases on MRI  that are either: 
A) Treatment naïve*  
or 
B) SRS+/- combination treated**  
and 
C) That fulfil the following criteria: 
 
1. Age ≥18. 
2. Target metastases size ≥  1cm. 
3. WHO performance status 0 – 2. 
4. If female, the subject is either post-menopausal (at least 1 year), or 
surgically sterilized (has had a documented bilateral oophorectomy 
and/or documented hysterectomy for at least 2 years), or if of 
childbearing potential, must have a negative urine beta human chorionic 
gonadotropin 
(β-HCG) 
pregnancy 
test 
done 
prior 
to 
tracer 
administration. 
5. The subject is able and willing to comply with study procedures, and 
signed and dated informed consent is obtained. 
6. The subject has a satisfactory medical history as judged by the 
investigator with no significant co-morbidities. 

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7. The subject’s clinical and laboratory tests are within normal limits and/or 
considered clinically insignificant. 
 
* Treatment Naïve = patients who have not and will not be undergoing treatment 
for  cerebral metastases at the time of the PET/MRI scan 
** SRS +/-combination therapy = patients who have completed the stereotactic 
radiosurgery (SRS) part of a combination regime  enabling a 4-8 week post SRS 
treatment 
PET/MRI 
scan. 
Combination 
therapy 
can 
be 
+/- 
chemotherapy/immunotherapy/targeted therapy.  
 
 
6.4  Exclusion Criteria 
Patients who meet all of the following exclusion criteria will not be considered 
eligible for this study: 
1. The subject is pregnant or lactating. 
2. Any other chronic illness that will or musculoskeletal condition that 
would  not allow comfortable performance of a PET study. 
3. Prior use within 14 days of enrolment or concurrent therapy with any 
other  investigational agent. 
4. Unsatisfactory renal function (eGFR<30). 
5. The subject has non-MRI compatible devices (e.g.a pacemaker, an 
implantable cardioverter-defibrillator (ICD), a nerve stimulator, a 
cochlear implant or a drug pump) or implanted material (e.g. non-MRI 
compatible sternal wires, biostimulators, metals or alloys). 
** A previous [18F]FPIA PET/MRI scan as part of the treatment naiive arm, is not 
an exlclusion for a second [18F]FPIA PET/MRI scan in the post SRS arm. 
 
 
6.5  ID Assignment  
Subject numbers will be assigned in successive order of inclusion. 
 
 
 

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7       STUDY PROCEDURES 
The patient procedures are summarized in Table 1 below.  
7.1  Schedule of Events               
Table 1. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
• 
1 If screening and PET/MRI are on same day – procedures do not have to 
be repeated. 
 
• 
2 If result available from routine test within 90 days of [18F]FPIA injection, this 
does not need to be repeated (determined by investigator). 
 
• 
3 In women of child bearing potential prior to injection of imaging agent. 
• 
4 24-hour post scan Adverse Event reporting period. 
 
Screening        
- 21 to day 0 
Pre-PET/MRI     
day 0 
[18F] FPIA Dose 
PET/MRI  
 
Informed Consent 
• 
 
 
 
 
Entry Criteria 
• 
 
 
 
 
Demographic Information 
• 
 
 
 
 
Medical History 
• 
 
 
 
 
WHO performance status 
• 
 
 
 
 
Height and Weight 
 
• 
 
 
 
Prior/Concomitant Medication 1 
• 
• 
 
 
 
Blood test for renal function2 
• 
 
 
 
 
Carnitine blood test 
 
• 
 
 
 
Pregnancy Test,3 
 
• 
 
 
 
Vital Signs  
 
• 
 
 
 
[18F]FPIA injection 
 
 
• 
 
 
Gadolinium contrast injection /kg (in 
2 stages) 
 
 
 
• 
 
Simultaneous PET/MRI Imaging* 
 
 
 
 
 
Adverse events4 
 
 
• 
• 
• 

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7.2  Screening Period 
Subjects will be screened up to 21 days before tracer administration to confirm 
eligibility.   
Signed and dated informed consent must be obtained from all subjects prior to any 
protocol specific procedures being performed. 
 
7.3  Screening Assessments 
7.3.1  Demographic Data and Medical History 
Demographic data and other characteristics will be recorded and will include date 
of birth, height, weight. 
A standard medical history will be obtained including details of previous cancer  
medication, surgical history and tumour characteristics. 
7.3.2  WHO Performance Status 
Performance status will be assessed at the scheduled time points indicated in 
Table 1 according to WHO criteria as follows: 
Table 2:  
 
0 
Fully active, able to carry on all pre‐disease activities without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature. For example, light housework, office work 
2 
Ambulatory and capable of all self‐care but unable to carry out any work activities. Up 
and about more than 50% of waking hours 
3 
Capable of only limited self‐care, confined to bed or chair 50% or more of waking hours 
4 
Completely disabled. Cannot carry on any self‐care. Totally confined to bed or chair 
5 
Death 
 
 
7.3.3  Pregnancy Test 
A urine pregnancy test will be performed prior to injection of imaging agent in 
women of child bearing potential.   
 

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7.3.4   Laboratory Evaluations 
Blood samples for renal function may have been taken as standard of care in this 
patient population. Results of blood tests taken within 90 days of the scan can be 
used for study purposes. A new blood sample will be taken if a result is not 
available. 
Blood will be taken for carnitine testing prior to the PET/MRI scan.   
7.3.5   Concomitant Medications 
Any concurrent, or procedural medications or therapy given to or taken by the 
subject from 2 weeks before inclusion into the study up to the end of the 
observation period will be recorded in the research notes. 
7.3.6   Vital Signs 
Blood pressure, pulse and temperature will be recorded. 
7.3.7   Follow Up period 
There is no PET/MRI related routine follow up. AEs will be reportable for up to 24 
hours post scan. The patients will be assessed and followed up in all routine 
clinical procedures as per local policy by the treating clinician.  
 
8       COMPLETION, WITHDRAWAL AND TERMINATION CRITERIA 
 
8.1   Completion 
8.1.1   Definition of completed subject  
A completed subject is one who has completed all imaging sequences of the 
combined [18F]FPIA PET/MRI protocol.  
8.1.2   Definition of an evaluable subject 
An evaluable subject is one who has completed study and where the images 
from the [18F]FPIA PET/MRI are of sufficient quality for analysis. 
In the case of subject withdrawal or non-evaluable subjects before or after dosing,  
additional subjects will be enrolled to reach 24 evaluable subjects.  

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8.1.3   Time on study 
The last study related visit for a subject would be the PET/MRI  scan. There are 
no follow up patient visits unless follow up for resolution of Adverse Events is 
required. 
Depending on the screening period taken in relation to the scan day, a subject can 
be on study between 2 and 23 days including a 24 hour post scan reportable 
Adverse event period.  
 
8.2  Rules for subject withdrawal 
There are no formal withdrawal criteria for this study.  During the conduct of the 
study, the study team will review the safety data for trends and signals that would 
indicate the need for withdrawal of a subject. 
In accordance with the Declaration of Helsinki, each subject is free to withdraw 
from the study at any time.  Investigator(s) also have the right to withdraw subjects 
from the study in the event of illness, AEs, or other reasons concerning the health 
or well-being of the subject, or in the case of lack of co-operation. Should a subject 
decide to withdraw after administration of the tracer, or should the investigator 
decide to withdraw the subject, all efforts will be made to complete and report the 
observations up to the time of withdrawal as thoroughly as possible.  A complete 
final evaluation at the time of the subject’s withdrawal will be made and an 
explanation given of why the subject is withdrawing or being withdrawn from the 
study.   
The reason for non-completion and the date and time of the last contact with the 
subject must be noted in the research documentation. If the reason for withdrawal 
is a clinical AE or an abnormal laboratory result, monitoring will continue until the 
outcome is evident.  The specific event or test result(s) must be recorded in the 
research documentation. In the case of subject withdrawal before or after dosing 
(i.e., non-evaluable subjects) additional subjects may be enrolled to reach a total 
of 24 evaluable subjects. 
 
8.3  Rules for terminating study 
The sponsor reserves the right to terminate the study at any time.  Prior to dosing 
of the first subject, the study may be terminated by the sponsor and the investigator 

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without consultation with the Administration of Radioactive Substances Advisory 
Committee (ARSAC) holder and Ethics Committee. The ARSAC holder, Ethics 
Committee and Health Research Authority (HRA), must be promptly notified that 
the study will no longer be taking place and provided with a detailed written 
explanation.  Once dosing with radiopharmaceutical has begun, the study may only 
be terminated if a careful review of the overall risk benefit analysis demonstrates 
that the assumptions have changed and that the overall balance is no longer 
acceptable. The investigators will temporarily halt the study if there has been a 
SAE which has been judged to be related to the study dosing. In these 
circumstances’ termination can only take place with the agreement of the Sponsor, 
ARSAC holder and the Ethics Committee. 
If it becomes necessary to consider termination of the study after dosing has 
begun, dosing may be suspended pending discussion between the sponsor, the 
investigator, the ARSAC holder and the Ethics Committee.  Dosing may always be 
immediately suspended for safety reasons. 
 
8.4  End of Study 
The end of the study is defined as the last visit of the last patient undergoing the 
study. 
9       RADIOTRACER AND IMAGING 
 
9.1  Radiopharmaceutical 
The [18F]FPIA radiotracer will be made to GMP standards at the Good 
Manufacturing Practice (GMP) Facility, University College London.   
Due to the short half-life of [18F]FPIA, the supply will be provided on a per-patient 
basis.  
[18F]FPIA will be packaged labelled and distributed by an appropriate courier to 
Invicro by the GMP Facility, University College London. Labels will be prepared in 
accordance with Good Manufacturing Practice Annex 13 requirements and local 
regulatory guidelines.  
The investigators are responsible for ensuring that deliveries of the tracer and 
study material are correctly received, recorded, handled and stored safely and 

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properly, in accordance with regulatory guidelines (ICH-GCP and Good 
Manufacturing Practice (GMP) and used in accordance with this protocol. 
 
9.2  Imaging Protocol 
• Patients taking part in this study will have either one or two [18F]FPIA 
PET/MRI scans 
• 
18F-FPIA PET/MRI imaging will be carried out at the Hammersmith Hospital 
site,within Invicro.  
• Pre-scan assessments will be carried out as per Table 1. 
• A peripheral venous cannula will be inserted within the arm for radiotracer 
and MRI contrast injections. 
• Simultaneous [18F]FPIA PET and MRI whole brain imaging (single bed 
position over the whole brain from vertex). 
• Following completion of imaging, the venous cannula will be removed at the 
end of the scan and patient will be discharged.  
• AEs will be reportable for up to 24 hours after the scan. 
 
9.3  PET Protocol 
• For the PET scan, a maximum of 370 MBq [18F]FPIA will be injected 
followed by a saline flush per scan. 
• PET data will be acquired immediately after tracer injection as a single-bed 
position (single bed position over the whole brain from vertex) with a 
dynamic imaging scan duration of 66 minutes. 
 
9.4  MRI Protocol 
The MRI protocol will include the following sequences: 
• Sequences for attenuation correction of PET data (DIXON, zero-TE) 
• Volumetric T1-weighted images, pre- and post-contrast administration 
• Volumetric T2 
• Dynamic susceptibility contrast perfusion (DSC)  
• Dynamic contrast enhanced perfusion (DCE) 
 

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The exact image acquisition parameters for sequences (e.g. TE, TR, flip angle) are 
hardware dependent and vary between scanner manufacturers and models, and 
are therefore not specified here. DWI sequences will be acquired prior to contrast 
agent administration. 
9.5  Radiation dosimetry  
The total ionising radiation exposure will be from the PET component of one 
PET/MRI scan.  There is no ionising radiation for the MRI component of the scan. 
 
 
 
Table 3: Radiation dose estimation 
 
Tracer 
[18F]FPIA PET 
Maximum [18F]FPIA injected 
activity  
370 MBq 
Conversion factor (mSv/MBq) 
0.0154* 
Total effective dose (mSv)/ 
patient for one  [18F]FPIA PET 
scan only 
5.7 mSv 
Total effective dose (mSv)/patient 
for two [18F]FPIA PET scans 
11.4 mSv 
 
*estimated Effective Dose of 18F-FPIA in humans to be 0.0154 mSv/MBq 
(Dubash et al, Manuscript in preparation). 
 
9.6  Radiation dose 
Each 
patient 
that 
participates 
in 
this 
study 
will 
have up 
to 
two 
additional PET/MRI scan in addition to their standard of care. If the patient is 
having radiotherapy (SRS) as part of their standard of care, the radiation dose 
estimated is 12-35Gy in 1-5 fractions. 

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For each PET MRI,  simultaneous 18F-FPIA PET and MRI whole brain imaging 
(vertex to C1 vertebral body) will be performed. 
There is no ionizing radiation from the MR component of the study only from the 
one PET scan. 
The maximum additional radiation dose associated with having 1 [18F]FPIA 
PET scan and is estimated to be 5.7mSv (from an administered activity of 370MBq 
of [18F]FPIA -which is similar to other common 18F PET imaging tracers).  
The radiation dose required by the study is additional to routine clinical care. The 
total protocol dose is 5.7mSv per scan. This is equivalent to 2 years and 6 months 
of average natural background radiation in the UK.  If you have 2 scans as part of 
this study, the total dose you will receive is 11.4 mSv, which is equivalant to 5 years 
of the average natural background radiation in the UK. Ionising radiation can cause 
cancer which manifests itself after many years or decades. The risk of developing 
cancer as a consequence of taking part in this study is estimated as 0.03% (1 in 
3,510) for one scan, and 0.06% (1 in 1,755) for 2 scans. 
For comparison, the natural lifetime cancer incidence in the general population is 
about 50% (1 in 2). 
For the patients having radiotherapy, the radiation dose from the [18F]FPIA 
PET/MRI scan will be very small compared to radiotherapy. 
  
9.7  Imaging Complications  
There are no immediate complications anticipated of the PET/MRI scan except for 
a potential mild bruising at the site of insertion of the peripheral cannula which 
should resolve within a few days .  Rarely,  the participant  feel may dizzy after the 
scan due to lying flat but this is normally short lived.   
MRI scanners use strong magnets, and therefore the subject will be given a safety 
questionnaire to complete and the study personnel will ask questions to make sure 
that you can safely have an MRI scan. As the MRI is noisy the subject will be given 
ear protection to wear. There is a risk of claustrophobia (fear of being in small 
places) associated with the scanner. 
A contrast agent (Gadolinium) will be used for the MRI scans which is injected 
intravenously. Some studies have shown gadolinium deposits in the brain and 
other tissues when using gadolinium contrast agents. There is no evidence that 

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this has caused any harm to patients and recommendations by the European 
Medicines Agency to use contrast agents with a lower risk of gadolinium deposition 
will be followed.  
Scans will be stopped at any time during the procedure if the subject is unable to 
tolerate it. 
 
10        ADVERSE EVENTS 
 
10.1  Definitions  
Adverse Event (AE): any untoward medical occurrence in a patient or clinical 
study subject. 
Serious Adverse Event (SAE): any untoward and unexpected medical 
occurrence or effect that:  
•   Results in death; 
•  Is life‐threatening*; 
• Requires hospitalisation or prolongation of existing inpatient’s     
hospitalisation**; 
•  Results in persistent or significant disability or incapacity; 
•  Is a congenital abnormality or birth defect; 
* “Life‐threatening” in the definition of “serious” refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe. 
** “Hospitalisation” means any unexpected admission to a hospital department. It 
does not usually apply to scheduled admissions that were planned before study 
inclusion or visits to casualty (without admission). 
Medical judgement should be exercised in deciding whether an adverse 
event/reaction is serious in other situations. Important adverse events/reactions 
that are not immediately life‐threatening, or do not result in death or hospitalisation 
but may jeopardise a patient or may require intervention to prevent one of the other 
outcomes listed in the definition above should also be considered serious. 

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10.2  Reporting of Adverse Events 
10.2.1 Non serious AEs 
  AEs will be collected from the start of each scan visit  to  up to 24 hours after 
each PET/CT scan.  
Any AEs which remain unresolved at the patient’s last visit in the study should be 
followed up by the Investigator for as long as medically indicated. 
Depending on the nature of the event the reporting procedures below should be 
followed. Any questions concerning adverse event reporting should be directed to 
the Chief Investigator in the first instance 
10.2.2 Serious AEs 
An SAE form should be sent to the Chief Investigator with 24 hours. However, 
relapse, death and/or hospitalisations for elective treatment of a pre-existing 
condition do not need reporting as SAEs.  
 
All SAEs will be reviewed by the Chief Investigator or a designated medically 
qualified representative to confirm expectedness and causality. 
 
All SAEs should be reported to the relevant REC where in the opinion of the Chief 
Investigator, the event was:  
 
• ‘Related’, i.e. resulted from the administration of any of the research procedures; 
and  
• ‘Unexpected’, i.e. an event that is not listed in the protocol as an expected 
occurrence  
 
Reports of related and unexpected SAEs should be submitted within 15 days of 
the Chief Investigator becoming aware of the event, using the NRES SAE form for 
non-IMP studies. The Chief Investigator must also notify the Sponsor of all SAEs.  
 
Local investigators should report any SAEs as required by their Local Research 
Ethics Committee, Sponsor and/or Research & Development Office. 
 
Please send SAE forms to the Sponsor and CI to the below email addresses: 
 

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11       STATISTICS AND DATA ANALYSES 
 
11.1  Statistical Design  
The study is an Observational Non-randomised Phase 2 study to determine the 
magnitude of the early steps of fatty acid oxidation in cerebral metastases using 
[18F]FPIA PET/MRI. This is the first time we are using FPIA in patients (with 
cerebral metastases), thus we do not know a priori the magnitude of uptake.  
Statistical tests will use a 0.05 significance level and will be 2-sided unless 
otherwise noted. 24 evaluable patients will be recruited for the study with the Upper 
Confidence Interval of sensitivity to detect fatty acid metabolism set to ≥ 90%.  
 
11.2  PET Analysis 
Dynamic PET attenuation corrected images will be reconstructed. Regions of 
interest (ROIs) corresponding to tumour and normal brain tissue will be drawn on 
summed images (e.g. 15 – 65 min), and used to generate. The ROIs will be used 
to derive semi-quantitative uptake parameters. These may include SUVmean (mean 
of standardized uptake values (SUV) within an ROI) normalised to body weight 
(bw), SUVmax and SUVpeak. 
11.3  Kinetic Analysis 
Contact details for reporting SAEs are as follows: 
 
 jrco@imperial.ac.uk (Sponsor E-mail) 
matt.williams3@nhs.net(CI E-mail) 
Tel: 020 3311 0733 
Please send SAE forms to the Sponsor and CI on the above email addresses: 
 (Mon to Fri 09.00 -17.00) 
 

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The kinetics of [18F]FPIA will be explored by visual inspection of regional time 
activity curves (TACs). If an adequate estimate of radioactivity in arterial plasma 
can be derived directly from delineation of an ROI in the field of view, then the use 
of image-derived input functions will be explored, along with modelling techniques 
such as compartmental analysis and / or graphical approaches to derive  
quantitative measures of tracer uptake. These may include the net irreversible 
plasma to tumour transfer constant (Ki, ml cm-3·min-1 , as well as compartmental 
analysis-derived [18F]FPIA delivery (K1, ml·cm-3·min-1 For comparison, tracer 
retention will also be estimated from SUV analysis (ratio of SUV at 60 min relative 
to 5 min). 
11.4  MRI Analysis 
MRI structural imaging sequences will be used for motion correction of PET data 
and to define tumour volumes using semi-automated intensity based segmentation 
algorithms such as those available in the software ‘Jim’. Perfusion data will be 
analysed using custom in-house image analysis tools and other software tools 
such as MATLAB, FSL, Nordic Neurolab and Tarquin. MRI and PET imaging 
parameters will be combined to develop novel biomarkers which can be used for 
tumour characterisation and assessment of treatment response.  
 
12       REGULATORY, ETHICAL AND LEGAL ISSUES  
 
12.1  Good Clinical Practice 
The study will be conducted in accordance with the guidelines laid down by the 
International Conference on Harmonisation for Good Clinical Practice (ICH GCP 
E6 guidelines). 
12.2  Ethics Approval 
Study approval has obtained from the South Central – Berkshire Research Ethics 
Committee (REC) and Health Regulator Authority (HRA). The study must also 
receive confirmation of capacity and capability from each participating NHS Trust 
before accepting participants into the study or any research activity is carried out. 
The study will be conducted in accordance with the recommendations for 
physicians involved in research on human subjects adopted by the 18th World 
Medical Assembly, Helsinki 1964 and later revisions. 
 

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12.3  Approval of Amendments 
Proposed amendments to the protocol and aforementioned documents must be 
submitted to the HRA/REC for approval as instructed by the Sponsor. 
Amendments requiring HRA/REC approval may be implemented only after a copy 
of the all necessary approval letters have been obtained. Imperial College London 
Sponsor approval is required before any amendments are made with the exception 
of urgent safety measures. Amendments that are intended to eliminate an 
apparent immediate hazard to subjects may be implemented prior to receiving 
Sponsor or REC approval. However, in this case, approval must be obtained as 
soon as possible after implementation. 
12.4  ARSAC Approval 
Employer and Practioner Administration of Radioactive Substances Advisory 
Committee (ARSAC) certificates will be required for the specified tracer and 
indication, and both the employer and practioner must be authorised to use this 
tracer for research purposes.  
 
The Chief Investigator will ensure that the procedures are compliant with the 
Ionising Radiation (Medical Exposure) Regulations, and appropriate review by a 
Medical Physics Expert and Clinical Radiation Expert has been undertaken. 
 
12.5  Informed Consent 
The Chief Investigator will: 
• Ensure that the right of the participant to refuse to participate without giving 
reasons is respected. 
 
• Ensure that each patient is given full and adequate oral and written 
information about the study including the background, purpose and 
risks/benefits of participation and the risk associated with the radiation 
exposure from the PET tracer. 
• Ensure that each patient is notified that they are free to withdraw from the 
study at any time without giving reasons and without prejudicing further 
treatment. 
• Ensure that each patient is given the opportunity to ask questions and 
allowed sufficient time to read and understand the information sheet. 

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• Ensure each patient provides signed, dated informed consent before 
undergoing any study specific procedure. 
• Ensure the original copy of the signed, dated Informed Consent Form is 
stored in the Investigator site file and a copy is also filed in the medical 
records. 
• Ensure that each patient receives a copy of the signed, dated Informed 
Consent Form. 
12.6  Indemnity 
Imperial College London holds negligent harm and non- negligent harm insurance 
policies, which apply to this study. 
12.7  Sponsor 
Imperial College London will act as the main Sponsor for this study. Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.  
12.8  Funding 
This study is funded by Medical Research Council (MRC). 
Patient travel expenses to attend study visits will be reimbursed where necessary. 
Patients will not be paid for taking part in the study. Patient travel expenses to 
attend study visits will be reimbursed where necessary or a taxi will be provided.  
12.9  Subject Confidentiality 
Imperial College London and Imperial College NHS Trust data protection policies 
will be followed. Subjects personal data will be available only to clinical and 
research members directly involved in the study conduct. The Chief Investigator 
will preserve the confidentiality of participants taking part in the study and is 
registered under the Data Protection Act. 
Participants will be allocated a unique study identifier code which will be known to 
the study research team and staff. The study identifier code will be used to 
pseudonymise samples, results, datasets and scans which would be held 
electronically on Imperial College London computers . 
Subjects’ identification data will be required for the recruitment, screening and 
registration processes. On study documents submitted to the Sponsor, patients 
will be identified by a trial ID number only. Documents that are not submitted to the 

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Sponsor (e.g. signed informed consent form) will be kept in a strictly confidential 
file by the investigator. 
The Chief  Investigator shall permit direct access to patients’ records and source 
document for the purposes of monitoring, auditing, or inspection by the Sponsor, 
authorised representatives of the Sponsor, Regulatory Authorities and REC. 
Invicro. staff will have access to limited participants' personal data for registration, 
IRMER, safety and governance purposes but may need to view the participant's 
medical records in the event of any study adverse events or emergencies on the 
scan day. This would be for the period of an event only and under the jurisdiction 
of the study investigator.   
The subject’s GP will be informed of their participation in the study. 
The taxi company will be given the name address & contact number of the subject 
by email or telephone. 
12.10  Material Storage and Analysis. 
Blood samples for renal function will be analysed by Imperial College Healthcare 
NHS Pathology department and  identifiable results reported on a secure web-
based results reporting system under the Imperial NHS Trust data protection 
policy, only accessible by NHS contracted staff. 
Carnitine plasma samples will be pseudonymised & stored frozen at Imperial 
College London. They will be sent to an external hospital laboratory for analysis 
and will not be identifiable to laboratory personnel.  
Urine samples for pregnancy testing will be pseudonymised and tested 
immediately by research staff.  
All samples will be disposed of after analysis according to local policies and will 
not be stored for future use.   
If the subject withdraws from the study, samples already taken as part of the 
research will be destroyed if the subject wishes, but data collected up to the 
withdrawal will be used. 
 
 

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13       DATA MANAGEMENT 
 
13.1  Data Recording and Storage 
All data except for the PET/MRI  scan will originate in the NHS. The principal 
means of data collection from patient visits will be imaging data obtained at 
Imperial College. This is uploaded fully pseudonymised to a dedicated electronic 
sharing system . Other screening, visit and follow up data will be collected on paper 
CRFs and collated on to an electronic database (excel spreadsheet) held on a 
secure, password protected computer within Imperial College Healthcare Trust, as 
required. Data will be pseudonymised and then stored on Imperial College secure 
servers and on encrypted drives in accordance with the data protection act. All 
data will be linked pseudonymised prior to being analysed and stored for 10 years. 
All paper/ manual study documentation including those with personal identifiers 
will be stored in an access controlled locked office within Imperial College London 
and Invicro.  
Subject’s original consent forms will be kept in the investigator site file in a 
controlled entry secure office at  Imperial College London ( Hammersmith 
campus). A copy of the consent forms will be kept in a investigator site file locked 
in a secure office at Invicro. for governance purposes and will also be copied to 
the medical records. 
Personal identifiable data collected at Invicro for registration, IRMER safety & 
governance purposes will be stored on an electronic Phase 1 system which is 
compliant with data protection registration. 
The Investigator must retain essential documents until notified by the Sponsor and 
at least for ten years after study completion. Documents should be stored in such 
a way that they can be accessed/data retrieved at a later date. The data for this 
study will be maintained on a secure, password protected Imperial College 
Healthcare Trust computer, with only authorised personnel having access to them. 
No study document will be destroyed without prior written agreement between the 
Sponsor and the CI. Should the CI wish to assign the study records to another 
party or move them to another location, written agreement must be obtained from 
the Sponsor. 
Data and images obtained from scans may be used in an anonymous form for 
future research, including that carried out by commercial healthcare companies. 
13.2  Audits and inspections 

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The study may be subject to inspection and audit by Imperial College London 
under their remit as sponsor, the Study Coordination Centre and other regulatory 
bodies to ensure adherence to GCP and the UK Policy Frame Work for Health and 
Social Care Research. 
13.3  Disclosure of Data  
Information concerning the study, patent applications, processes, scientific data or 
other pertinent information is confidential and remains the property of the Sponsor. 
The investigator may use this information for the purposes of the study only. 
All data information obtained as a result of the study will be regarded as 
CONFIDENTIAL, at least until appropriate analysis and review by the 
investigator(s) is completed. 
 
14       STUDY MANAGEMENT 
The day-to-day management of the study will be co-ordinated through the Imaging 
research office, Imperial College London,  GN1, Commonwealth Building, 
Hammersmith Campus, Du Cane Rd, London, W12 0NN. 
 
15       PUBLICATION AND DISSEMINATION  
 
The results of the study will be written and will be submitted for publication to a 
suitable peer reviewed journal. Results may be presented at conferences and 
internally within the Sponsor institution. A final summary of results will be provided 
to the REC. All data will be anonymised for publication and no identifiable personal 
data will be used. 
 
Patients will have the opportunity of being informed when data is published, if they 
wish. 
 
 
 
 
 
 
 

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16       REFERENCES 
 
[1]  Tsao, M. N., Rades, D., Wirth, A., Lo, S. S., Danielson, B. L., Gaspar, L. E., … 
Chang, E. L. (2012). Radiotherapeutic and surgical management for newly 
diagnosed brain metastasis(es): An American Society for Radiation Oncology 
evidence-based guideline. Practical Radiation Oncology, 2(3), 210–225. 
https://doi.org/10.1016/j.prro.2011.12.004 
[3]  T. Mashimo et al., “Acetate Is a Bioenergetic Substrate for Human 
Glioblastoma and Brain Metastases,” Cell, vol. 159, no. 7, pp. 1603–1614, Dec. 
2014.  
[4]  Z. T. Schug et al., “Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and 
Maintains Cancer Cell Growth under Metabolic Stress,” Cancer Cell, vol. 27, no. 
1, pp. 57–71, Jan. 2015.  
[5]  T. H. Witney et al., “Preclinical Evaluation of 3-18F-Fluoro-2,2- 
Dimethylpropionic Acid as an Imaging Agent for Tumor Detection,” J. Nucl. Med. , 
vol. 55, no. 9, pp. 1506–1512, Sep. 2014.