TY - JOUR
T1 - Imaging paclitaxel (chemotherapy)-induced tumor apoptosis with 99mTc C2A, a domain of synaptotagmin I
T2 - a preliminary study
AU - Wang, Feng
AU - Fang, Wei
AU - Zhao, Ming
AU - Wang, Zizheng
AU - Ji, Shundong
AU - Li, Yan
AU - Zheng, Yuming
N1 - Funding Information:
We are grateful to Prof. A. Cahid Civelek (Division of Nuclear Medicine, Saint Louis University) for his valuable advice and assistance in the revision of the manuscript. This research was supported by grants from Jiangsu Government Science (grant BS2006010) and National Nature Science Foundation of China (grant 30700186, 30500134).
PY - 2008/4
Y1 - 2008/4
N2 - Purpose: 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. Materials and 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). Conclusion: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using 99mTc-labeled C2A.
AB - Purpose: 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. Materials and 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). Conclusion: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using 99mTc-labeled C2A.
KW - Apoptosis
KW - C2A domain
KW - Non-small cell lung cancer
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U2 - 10.1016/j.nucmedbio.2007.12.007
DO - 10.1016/j.nucmedbio.2007.12.007
M3 - Article
C2 - 18355692
AN - SCOPUS:40749117682
SN - 0969-8051
VL - 35
SP - 359
EP - 364
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 3
ER -