RT Journal Article SR Electronic T1 Thymidine Metabolism as a Confounding Factor for 3′-Deoxy-3′-18F-Fluorothymidine Uptake After Therapy in a Colorectal Cancer Model JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1063 OP 1069 DO 10.2967/jnumed.117.206250 VO 59 IS 7 A1 Sonja Schelhaas A1 Lydia Wachsmuth A1 Sven Hermann A1 Natascha Rieder A1 Astrid Heller A1 Kathrin Heinzmann A1 Davina J. Honess A1 Donna-Michelle Smith A1 Inga B. Fricke A1 Nathalie Just A1 Sabrina Doblas A1 Ralph Sinkus A1 Christian Döring A1 Klaus P. Schäfers A1 John R. Griffiths A1 Cornelius Faber A1 Richard Schneider A1 Eric O. Aboagye A1 Andreas H. Jacobs YR 2018 UL http://jnm.snmjournals.org/content/59/7/1063.abstract 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.