Clinical trial NCT00804544: 99mTc-MIBI SPECT/CT in Breast Malignancy
Official title: Tc-99m Sestamibi SPECT/CT for Prediction of the Response of Locally Advanced Breast Malignancy to Neoadjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Breast Cancer
Keywords: Integrated SPECT/CT
99mTc-sestMIBI
Chemosensitivity
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2008-12-09
Enrollment: 4
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 99mTc-SestaMIBI mammoscintigraphy (MMS) may be used in patients with locally advanced breast cancer (LABC) scheduled for neoadjuvant chemotherapy. MMS may be performed for 1) nodal staging of axillary lymph node metastases, 2) prediction of chemosensitivity or Pgp/MDR-1 mediated chemoresistance, and 3) evaluation of efficacy to chemotherapy and radiation therapy.

MMS is routinely performed with planar/SPECT imaging according to the Society of Nuclear Medicine and European Association of Nuclear Medicine guidelines.

In this pilot study, an optimised acquisition protocol will be setup with SPECT/low-dose multislice CT in addition to planar imaging.

Detailed description: 99mTc-SestaMIBI is a lipophylic cation as many cytotoxic chemotherapy drugs (i.e. anthracyclines, inhibitor of topoisomerase II, antimicrotubule, vinca alkaloids, inhibitors of DNA replication) accumulating in the mitochondria of tumour cells. MIBI tumour uptake is related to viability and proliferation due to increased perfusion and increased energy-dependent metabolism.

99mTc-SestaMIBI is a substrate for the glycoprotein P (Pgp) pump encoded by the multidrug resistance gene -1 (MDR-1). MIBI tumour uptake with no significant wash-out over time (\<45% at 3H) predicts a chemosensitivity with no Pgp/MDR-1 overexpression. MIBI efflux with no significant tumour uptake predicts efflux of chemotherapy drugs from the tumour cells related to Pgp/MDR-1 overexpression or to anti-apoptotic Bcl-2 overexpression. Early MIBI efflux (\< 1H) may also be related to pro-apoptotic Bax overexpression.

SPECT/CT will be used for anatomic localisation and and attenuation correction. CT from SPECT/CT is a low-dose (\< 2 mSv) multislice CT (4 slice). SPECT/CT will also be used for correction of image-degrading factors including collimator-detector-response compensation for resolution recovery, and scatter correction. SPECT/CT based absolute semi-quantification of MIBI uptake into primary tumour and lymph nodes (i.e. standardised uptake value or SUV) will also be performed.

SPECT/CT optimised imaging will be compared to planar/SPECT conventional nuclear imaging for 1) detection of MIBI-avid primary breast tumour and lymph node metastases, 2) semi-quantification of MIBI uptake (T/B, SUV, and %wash-out) into primary breast tumour and lymph node metastases, 3) prediction of chemosensitivity at baseline, 3) Evaluation of chemotherapy efficacy after the first course of chemotherapy (after 2 weeks) compared to clinical response and histo-pathological response.

SPECT/CT mammoscintigraphy findings will be compared to clinical findings (palpation), radiological findings (mammography, US, MRI), and histo-pathological findings (Pgp/MDR-1 expression) into tumours after surgery.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically proven breast cancer
* Patients with locally advanced breast cancer (stages T2-4 N0-3 M0)
* Patients scheduled for neoadjuvant chemotherapy
* Patients scheduled for radical modified mastectomy
* Patients with no physical and/or psychological contraindications
* Patients with no recent nuclear medicine study using long-lived isotopes (i.e. 67Ga, 111In, 131I) within the 48 hour preceding the mammoscintigraphy

Exclusion Criteria:

* Patient with no histologically proven breast cancer
* Patients with early stage T1 breast cancer
* Patients who are not candidates for neoadjuvant chemotherapy
* Patients who are not surgical candidates
* Patients with physical and/or psychological contraindications
* Pregnant or breast feeding patients
* Patients with a recent nuclear medicine study using long-lived isotopes (i.e. 67Ga, 111In, 131I) within the 48 hour preceding the mammoscintigraphy

Primary outcomes:
measure: 1- Nodal staging 2- Prediction of chemosensitivity 3- Evaluation of chemosensitivity
timeFrame: 1 year
Secondary outcomes:
measure: Added-Value of integrated SPECT/Low-dose MultiSlice CT versus planar/SPECT imaging in mammoscintigraphy with 99mTc-SestaMIBI
timeFrame: 1 year
Other outcomes:
Locations:
city: London
country: Canada
facility: South Street Hospital - Department of Nuclear Medicine
state: Ontario
Study officials:
affiliation: The UWO - LHSC - Department of Nuclear Medicine
name: Irina Rachinsky, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: The UWO -LHSC - Department of Nuclear Medicine
name: Albert A Driedger, MD, PhD
role: STUDY_CHAIR
affiliation: The UWO - LHSC - Department of General Surgery
name: Muriel Brackstone, MD
role: STUDY_DIRECTOR
affiliation: The UWO - LHSC - Department of Medical Oncology
name: Francisco Perera, MD
role: STUDY_DIRECTOR
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