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

Feng Wang*, Wei Fang, Ming Zhao, Zizheng Wang, Shundong Ji, Yan Li, Yuming Zheng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
JournalNuclear Medicine and Biology
Volume35
Issue number3
DOIs
StatePublished - Apr 2008

Funding

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).

Keywords

  • Apoptosis
  • C2A domain
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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