PT  - JOURNAL ARTICLE
AU  - Witney, Timothy H.
AU  - Hoehne, Aileen
AU  - Reeves, Robert E.
AU  - Ilovich, Ohad
AU  - Namavari, Mohammad
AU  - Shen, Bin
AU  - Chin, Frederick T.
AU  - Rao, Jianghong
AU  - Gambhir, Sanjiv S.
TI  - A Systematic Comparison of <sup>18</sup>F-C-SNAT to Established Radiotracer Imaging Agents for the Detection of Tumor Response to Treatment
DP  - 2015 May 13
TA  - Clinical Cancer Research
4099  - http://clincancerres.aacrjournals.org/content/early/2015/07/16/1078-0432.CCR-14-3176.short
4100  - http://clincancerres.aacrjournals.org/content/early/2015/07/16/1078-0432.CCR-14-3176.full
AB  - 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 18F-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 18F-C-SNAT for the detection of drug-induced cell death to clinically evaluated radiotracers, 18F-FDG, 99mTc-Annexin V, and 18F-ML-10 in tumor cells in culture, and in tumor-bearing mice in vivo.Results: In drug-treated lymphoma cells, 18F-FDG, 99mTc-Annexin V, and 18F-C-SNAT cell-associated radioactivity correlated well to levels of cell death (R 2 > 0.8; P < 0.001), with no correlation measured for 18F-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 99mTc-Annexin V and 18F-C-SNAT were increased 1.4- and 2.1-fold, respectively, in drug-treated versus naïve control animals (P < 0.05), although 99mTc-Annexin V binding did not correlate to ex vivo TUNEL staining of tissue sections. A differential response was not observed with either 18F-FDG or 18F-ML-10.Conclusions: We have demonstrated here that 18F-C-SNAT can sensitively detect drug-induced cell death in murine lymphoma and human NSCLC. Despite favorable image contrast obtained with 18F-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. Clin Cancer Res; 1–10. ©2015 AACR.