Imaging paclitaxel (chemotherapy)-induced tumor apoptosis with 99mTc C2A, a domain of synaptotagmin I: a preliminary study.
OBJECTIVE
To evaluate the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using 99mTc-labeled C2A domain of synaptotagmin I in a mouse model.


METHODS
H460 tumor-bearing mice were treated with intravenous paclitaxel, and 12, 24, 48 and 72 h later, 99mTc-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 ROI analysis and reflected specific binding of 99mTc-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 1 % 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).


CONCLUSIONS
This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using 99mTc-labeled C2A.
Wang
Feng
F
Nanjing First Hospital affiliated to Nanjing Medical University, Nanjing 210006, China. fengwang1972cn@yahoo.com.cn
Fang
Wei
W
Zhao
Ming
M
Wang
Zizheng
Z
Ji
Shundong
S
Li
Yan
Y
Zheng
Yuming
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D011869:Radioligand Assay / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050863:Synaptotagmin I / Q000737:chemistry* / Q000187:drug effects; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D019275:Radiopharmaceuticals; D050863:Synaptotagmin I; D013667:Technetium; C505409:Casp3 protein, mouse; D053148:Caspase 3; D017239:Paclitaxel