[Technetium-99m labeled synaptotagmin I C2A detection of paclitaxel-induced apoptosis in non-small cell lung cancer].
Objective To evaluate the efficacy of 99mTc-labeled C2A probe in detection of apoptosis of non-small cell lung cancer (NSCLC) cells after chemotherapy.


METHODS
Imaging studies were performed in NSCLC H460-bearing mice. The mice were divided into 2 groups: the paclitaxel-treated group and control group. 99mTc-C2A was injected intravenously at 12, 24, 48 and 72 h after chemotherapy. Images were acquired at 3 h and 6 h after injection using a pinhole collimator. The regions of interest (ROI) were drawn in tumor area and contralateral nomal tissue, and the ratio of T/NT were caculated. The tumor sections were stained by HE and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-nick-end labeling) staining to confirm the presence of apoptosis. Activated caspase-3 was also analyzed with flow cytometry.


RESULTS
Little uptake of 99mTc-C2A was found in baseline images, but tumor uptake increased very much after chemotherapy, the T/NT ratio was 1.79 +/- 0.34, 2.23 +/- 0.33 and 2.78 +/- 0.34, respectively. The T/NT ratio of control was 1.48 +/- 0.23. Tumor uptake (% ID/g) of 99mTc-C2A in chemotherapy groups were 2.82 +/- 0.90, 3.13 +/- 0.48 and 3.52 +/- 1.18, respectively. Tumor uptake (% ID/g) in the control group was 1.21 +/- 0.51. It in paclitaxel-treatment groups were 2.82 +/- 0.90, 3.13 +/- 0.48 and 3.51 +/- 1.18, respectively, significantly higher than that in untreated mice. Furthermore, the uptake of 99mTc-C2A correlated well with apoptotic index (r = 0.56, P < 0.01), and activated caspase-3 (r = 0.59, P < 0.01).


CONCLUSIONS
Our preliminary results demonstrated that 99mTc-C2A imaging in vivo for detection of cell death in solid tumors is feasible and well correlated with TUNEL staining and activated caspase-3. The C2A holds promise and warrants further development as a molecular probe to early predict cancer treatment efficacy.
Wang
Feng
F
Department of Nuclear Medcine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. fengwangcn@hotmail.com
Fang
Wei
W
Ji
Shun-dong
SD
Meng
Qing-le
QL
Li
Yan
Y
Fan
Ke-wu
KW
Wang
Zi-zheng
ZZ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D050863:Synaptotagmin I / Q000737:chemistry / Q000378:metabolism*; D013667:Technetium / Q000008:administration & dosage / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D050863:Synaptotagmin I; D013667:Technetium; D053148:Caspase 3; D017239:Paclitaxel