TY - JOUR T1 - Thymidine Metabolism as a Confounding Factor for 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine Uptake After Therapy in a Colorectal Cancer Model JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1063 LP - 1069 DO - 10.2967/jnumed.117.206250 VL - 59 IS - 7 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 Y1 - 2018/07/01 UR - http://jnm.snmjournals.org/content/59/7/1063.abstract N2 - 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. ER -