Imaging paclitaxel (chemotherapy)-induced tumor apoptosis with Tc-99m C2A, a domain of synaptotagmin I: a preliminary study

Purpose: To evaluate the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using Tc-99m-labeled C2A domain of synaptotagmin I in a mouse model, Materials and Methods: H460 tumor-bearing mice were treated with intravenous paclitaxel, and 12, 24, 48 and 72 h later, Tc-99m-C2A-GST was injected intravenously, and planar images were acquired at 2, 4 and 6 h postinjection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROT analysis and reflected specific binding of Tc-99m-C2A-GST. Mice were sacrificed after 6-h imaging; caspase-3 as apoptosis executer was determined by flow cytometry; DNA fragmentation was analyzed by terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Whereas nonspecific accumulation was estimated using inactivated C2A-GST. The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity. Results: T/NT significantly increased after paclitaxel inducement, whereas it was low in untreated tumors (T/NT=1.24 +/- 0.23). In terms of % ID/g, activity in Group 2 (12 h), Group 3 (24 h), Group 4 (48 h) and Group 5 (72 h) after the treatment was 2.05 +/- 0.20, 3.02 +/- 1.01, 3.17 +/- 1.16 and 3.96 +/- 1.72, respectively. Whereas in the nontreated group, Group I % ID/g was 1.21 +/- 0.51. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.70, P<01), as well as caspase-3 activity (r = 0.75, P<01). Conclusion: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using Tc-99m-labeled C2A. (C) 2008 Elsevier Inc. All rights reserved.