科研之友
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摘要
Purpose: An early readout of tumor response to therapy through measurement of drug or radiation-induced cell death may provide important prognostic indications and improved patient management. It has been shown that the uptake of F-18-C-SNAT can be used to detect early response to therapy in tumors by positron emission tomography (PET) via a mechanism of caspase-3-triggered nanoaggregation. Experimental Design: Here, we compared the preclinical utility of F-18-C-SNAT for the detection of drug-induced cell death to clinically evaluated radiotracers, F-18-FDG, Tc-99m-Annexin V, and F-18-ML-10 in tumor cells in culture, and in tumor-bearing mice in vivo. Results: In drug-treated lymphoma cells, F-18-FDG, Tc-99m-Annexin V, and F-18-C-SNAT cell-associated radioactivity correlated well to levels of cell death (R-2 > 0.8; P < 0.001), with no correlation measured for F-18-ML-10 (R-2 = 0.05; P > 0.05). A similar pattern of response was observed in two human NSCLC cell lines following carboplatin treatment. EL-4 tumor uptake of Tc-99m-Annexin V and F-18-C-SNAT were increased 1.4-and 2.1-fold, respectively, in drug-treated versus naive control animals (P < 0.05), although Tc-99m-Annexin V binding did not correlate to ex vivo TUNEL staining of tissue sections. A differential response was not observed with either F-18-FDG or F-18-ML-10. Conclusions: We have demonstrated here that F-18-C-SNAT can sensitively detect drug-induced cell death in murine lymphoma and human NSCLC. Despite favorable image contrast obtained with F-18-C-SNAT, the development of next-generation derivatives, using the same novel and promising uptake mechanism, but displaying improved biodistribution profiles, are warranted for maximum clinical utility.
- 出版日期2015-9-1
