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

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.

• Authors: Feng Wang, Wei Fang, Ming Zhao, Zizheng Wang, Shundong Ji, Yan Li, Yuming Zheng
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 35 Issue 3 Pg. 359-64 (Apr 2008) ISSN: 0969-8051 [Print] United States
• PMID: 18355692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Radiopharmaceuticals
• Synaptotagmin I
• Technetium
• Casp3 protein, mouse
• Caspase 3
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy)
• Caspase 3 (drug effects, metabolism)
• Cell Line, Tumor
• DNA Fragmentation (drug effects)
• Disease Models, Animal
• Female
• Humans
• Injections, Intravenous
• Lung Neoplasms (diagnostic imaging, drug therapy)
• Male
• Mice
• Paclitaxel (therapeutic use)
• Protein Structure, Tertiary
• Radioligand Assay (methods)
• Radionuclide Imaging
• Radiopharmaceuticals (pharmacokinetics)
• Synaptotagmin I (chemistry, drug effects)
• Technetium (pharmacokinetics)
• Tissue Distribution