PT - JOURNAL ARTICLE AU - Sonja Schelhaas AU - Lydia Wachsmuth AU - Sven Hermann AU - Natascha Rieder AU - Astrid Heller AU - Kathrin Heinzmann AU - Davina J. Honess AU - Donna-Michelle Smith AU - Inga B. Fricke AU - Nathalie Just AU - Sabrina Doblas AU - Ralph Sinkus AU - Christian Döring AU - Klaus P. Schäfers AU - John R. Griffiths AU - Cornelius Faber AU - Richard Schneider AU - Eric O. Aboagye AU - Andreas H. Jacobs TI - Thymidine Metabolism as a Confounding Factor for 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine Uptake After Therapy in a Colorectal Cancer Model AID - 10.2967/jnumed.117.206250 DP - 2018 Jul 01 TA - Journal of Nuclear Medicine PG - 1063--1069 VI - 59 IP - 7 4099 - http://jnm.snmjournals.org/content/59/7/1063.short 4100 - http://jnm.snmjournals.org/content/59/7/1063.full SO - J Nucl Med2018 Jul 01; 59 AB - Noninvasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential PET and diffusion-weighted MRI to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Methods: Tumor-bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 colorectal cancer xenografts, were treated with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) weekly. On days 1, 2, 6, 9, and 13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on day 1 of therapy. Results: In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) accompanied by increases in markers for proliferation (Ki-67, thymidine kinase 1) and for activated DNA damage response (γH2AX), whereas the effect on cell death was minimal. Because tracer uptake was unaltered in the HCT116 model, these changes appear to be specific for tumor response. Conclusion: We demonstrated that 18F-FLT PET can noninvasively monitor cancer treatment–induced molecular alterations, including thymidine metabolism and DNA damage response. The cellular or imaging changes may not, however, be directly related to therapy response as assessed by volumetric measurements.