99mTc]Tc-duramycin, a potential molecular probe for early prediction of tumor response after chemotherapy

Abstract

ObjectiveApoptosis plays a crucial role in many biological processes, especially in cancer. However, real-time monitoring of apoptosis is challenging. [99mTc]duramycin can selectively target an apoptosis biomarker: phosphatidylethanolamine (PE), which is normally located on the intracellular cell-membrane surface but redistributes onto the outer cell-membrane upon apoptosis. Therefore, 99mTc-duramycin is a potential probe for non-invasive detection of apoptosis in real-time. The aim of this study was to evaluate the value of [99mTc]duramycin for detecting early apoptotic response in tumors after chemotherapy, thus providing a tool for early prediction of curative effects in tumors. MethodsHuman breast cancer MDA-MB-468 model mice, randomly divided into two groups, were injected with cisplatin or vehicle once per day. [99mTc]duramycin imaging was performed for group 1 before treatment and 24 h after the third day of treatment to evaluate treatment response through animal single-photon emission computed tomography (SPECT/CT). Mice in group 2 were treated for 10 days consecutively, to observe treatment response by tumor volume changes. Treatment response was further demonstrated through TdT-mediated dUTP nick-end labeling (TUNEL) and cleaved caspase-3 (CC3). Results[99mTc]duramycin uptake in MDA-MB-468 tumors was significantly higher in the treatment group than the control group after as few as 3 days of cisplatin treatment (p = 0.0001), and it also increased after treatment as comparison with that before treatment (p = 0.0001). Moreover, [99mTc]duramycin uptake in tumors clearly correlated with immunohistochemistry results (TUNEL: r = 0.892, p = 0.0001, and CC3: r = 0.89, p = 0.0001). Additionally, tumor size reduction, indicating effective treatment, was not observed until the eighth day after treatment, far later than the time when diagnosis could be made through [99mTc]duramycin imaging. Conclusions[99mTc]duramycin SPECT/CT provides a non-invasive molecular imaging strategy for early detection of tumor apoptosis after chemotherapy and thus may have great potential value in the clinic.