Pathological complete response to the
neoadjuvant therapy (
NAT) for
triple negative breast cancer (TNBC) is predictive of prolonged patient survival. Methods for early evaluation of
NAT efficiency are still needed, in order to rapidly adjust the therapeutic strategy in case of initial non-response. One option for this is molecular imaging of apoptosis induced by
chemotherapy. Therefore, we investigated the capacity of [18F]ML-10 PET imaging, an apoptosis radiotracer, to detect
tumor cell apoptosis and early predict the therapeutic response of human TNBC.
RESULTS: Initially, the induction of apoptosis by different
therapies was quantified. We confirmed, in vitro, that
paclitaxel or
epirubicin, the fundamental cytotoxic drugs for
breast cancer, induce apoptosis in TNBC cell lines. Exposure of TNBC models MDA-MB-231 and MDA-MB-468 to these drugs induced a significant increase (p < 0.01) of the apoptotic hallmarks: DNA fragmentation, membrane
phospholipid scrambling, and PARP activation. Secondarily, apoptotic fraction was compared to the intracellular accumulation of the radiotracer. [18F]ML-10 accumulated in the apoptotic cells after 72 h of treatment by
paclitaxel in vitro; this accumulation positively correlated with the apoptotic fraction. In vivo, [18F]ML-10 was rapidly cleared from the nontarget organs and mainly eliminated by the kidneys. Comparison of the in vivo [18F]FDG, [18F]
FMISO, and [18F]ML-10 uptakes revealed that the
tumor accumulation of [18F]ML-10 was directly related to the tumor hypoxia level. Finally, after the in vivo treatment of TNBC murine xenografts by
paclitaxel, apoptosis was well induced, as demonstrated by the cleaved
caspase-3 levels; however, no significant increase of [18F]ML-10 accumulation in the
tumors was observed, either on day 3 or day 6 after the end of the treatment.
CONCLUSIONS: These results highlighted that PET imaging using [18F]ML-10 allows the visualization of apoptotic cells in TNBC models. Nevertheless, the increase of the
chemotherapy-induced apoptotic response when using
paclitaxel could not be assessed using this radiotracer in our mouse model.