Recently, companion diagnostics with nuclear medicine techniques have been anticipated as more suitable means than biopsy for predicting treatment efficacy. The anti-cancer 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, 123 I-5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ( 123 I-IIMU),

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... uld predict the efficacy of capecitabine treatment. Methods: Sensitivity to doxifluridine, a metabolite of capecitabine and direct substrate for TP, was assessed by WST assays in vitro for three human colon cancer cell lines with different TP expression profiles. The intracellular uptake and retention of 123 I-IIMU were evaluated. Mice inoculated with each cell line were treated with capecitabine for 2 weeks, and tumor growth was compared. In vivo distribution studies and single photon emission computed tomography/computed tomography imaging of 123 I-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 123 I-IIMU were dependent on TP expression levels. In vivo experiments in inoculated mice showed that 123 I-IIMU accumulation in tumor tissue was in line with TP expression levels and susceptibility to capecitabine treatment. Moreover, single photon emission computed tomography/computed tomography imaging of 123 I-IIMU in tumor-inoculated mice showed that 123 I-IIMU by on August 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from 4 reflects TP expression levels in tumor tissues. Conclusion: 123 I-IIMU could be used as an in vivo companion diagnostic for predicting the efficacy of capecitabine treatment.