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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: UNLABELLED, METHODS, RESULTS. Meshes: 5'-Nucleotidase, Animals, Capecitabine, Cell Line, Tumor, Colonic Neoplasms, Drug Monitoring, Female, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Molecular Imaging, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Single Photon Emission Computed Tomography Computed Tomography, Treatment Outcome.
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Does the Thymidine Phosphorylase Imaging Agent 123I-IIMU predict the Efficacy of Capecitabine? Context: 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, (123)I-5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ((123)I-IIMU), could predict the efficacy of capecitabine treatment. 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 (123)I-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 (123)I-IIMU were performed in inoculated mice. 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, SPECT/CT imaging of (123)I-IIMU in tumor-inoculated mice showed that (123)I-IIMU reflects TP expression levels in tumor tissues.
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(123)I-IIMU could be used as an in vivo companion diagnostic for predicting the efficacy of capecitabine treatment. Final Decision: yes