Trial Information

Tc-99m Sestamibi SPECT/CT for Prediction of the Response of Locally Advanced Breast Malignancy to Neoadjuvant Chemotherapy

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.