RT Journal Article SR Electronic T1 The Thymidine Phosphorylase Imaging Agent 123I-IIMU Predicts the Efficacy of Capecitabine JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1276 OP 1281 DO 10.2967/jnumed.115.165811 VO 57 IS 8 A1 Kobashi, Nobuya A1 Matsumoto, Hiroki A1 Zhao, Songji A1 Meike, Shunsuke A1 Okumura, Yuki A1 Abe, Tsutomu A1 Akizawa, Hiromichi A1 Ohkura, Kazue A1 Nishijima, Ken-ichi A1 Tamaki, Nagara A1 Kuge, Yuji YR 2016 UL http://jnm.snmjournals.org/content/57/8/1276.abstract AB Recently, companion diagnostics with nuclear medicine techniques have been anticipated as more suitable means than biopsy for predicting treatment efficacy. The anticancer effect of capecitabine, an orally administered chemotherapeutic agent activated by thymidine phosphorylase (TP), is positively associated with tumor TP expression levels. This study aimed to assess whether TP imaging using a radiolabeled uracil derivative, 123I-5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (123I-IIMU), could predict the efficacy of capecitabine treatment. Methods: Sensitivity to doxifluridine, a metabolite of capecitabine and direct substrate for TP, was assessed by water-soluble tetrazolium salt assays in vitro for 3 human colon cancer cell lines with different TP expression profiles. The intracellular uptake and retention of 123I-IIMU were evaluated. Mice inoculated with each cell line were treated with capecitabine for 2 wk, and tumor growth was compared. In vivo distribution studies and SPECT/CT imaging of 123I-IIMU were performed in inoculated mice. Results: In vitro experiments showed a positive relation between TP expression levels and doxifluridine sensitivity. In vitro studies revealed that intracellular uptake and retention of 123I-IIMU were dependent on TP expression levels. In vivo experiments in inoculated mice showed that 123I-IIMU accumulation in tumor tissue was in line with TP expression levels and susceptibility to capecitabine treatment. Moreover, SPECT/CT imaging of 123I-IIMU in tumor-inoculated mice showed that 123I-IIMU reflects TP expression levels in tumor tissues. Conclusion: 123I-IIMU could be used as an in vivo companion diagnostic for predicting the efficacy of capecitabine treatment.