Abstract
1100
Background: Therapy-induced apoptosis in vivo has been shown to improve tumor response and to correlate with subsequent outcome. Targeted therapy using antibody (AMG-655, a fully human IgG1 mAb, targeted death receptor DR5), has been shown to induce apoptosis in cell lines derived from colon and pancreatic cancers, as well as in vivo models of human cancer such as colorectal cancer. Duramycin is a 19-amino acid peptide that can identify apoptotic cells by targeting phosphatidylethanolamine (PE). Our objective was to evaluate colorectal cancer response to anti-DR5 targeted therapy by imaging early apoptosis using 18F-duramycin. Methods: Female nude mice (n=6) were subcutaneously injected with luciferase-transfected HT29 cells and COLO205 cells into the left and right shoulder of the mouse respectively. When tumors reached about 6-7 mm in diameter, bioluminescent imaging (BLI) was performed, followed by imaging on a microPET-R4 scanner and a microCAT-II scanner. 200 µCi of 18F-Al-duramycin was injected into each mouse via the tail vein. PET/CT baseline imaging was performed 1 h post-injection. Immediately after imaging, AMG655 (1.5 mg/kg) was injected IP into each mouse. BLI and PET/CT imaging were repeated 24 h post treatment. After imaging was completed, all the mice were then sacrificed for biodistribution studies. Results: BLI data showed that COLO205 tumor responded to drug treatment better than that of HT29, with about 15-20% more BLI signal reduction in 4 out of 6 mice. Uptake ratios for COLO205/HT29 tumors as shown by PET imaging were 1.1±0.5 and 2.0±0.3 at baseline and 24 h post-treatment, respectively. Biodistribution data showed comparable results with uptake ratio (COLO205/HT29) of 2.9 after treatment. In addition, both PET and biodistribution studies revealed significant tracer accumulation in liver, kidney and spleen.
Conclusions: Our preliminary data demonstrated that 18F-duramycin targeted drug-sensitive COLO205 tumor but not drug-resistant HT29 tumor and holds promise as a useful tool to monitor early tumor response to anti-DR5 targeted therapy.