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Repurposing [C]MC1 for PET Imaging of Cyclooxygenase-2 in Colorectal Cancer Xenograft Mouse Models. | LitMetric
Purpose : Cyclooxygenase-2 (COX-2) is a target for inflammation and colorectal cancer (CRC). This study evaluated the COX-2 neuro-PET radiopharmaceutical, [C]MC1, in CRC xenograft mice.Procedures : [C]MC1 was evaluated in ICRscid mice with HT-29 and HCT-116 CRC xenografts, with high and low COX-2 expression, respectively, by immunohistochemistry, cellular uptake, dynamic PET/MR imaging, ex vivo biodistribution, and radiometabolite analysis.Results : HT-29 xenografts were well visualized with [C]MC1 using PET/MR. Time-activity curves revealed steady tumor radioactivity accumulation in HT-29 xenografts that plateaued from 40 to 60 min (3.07 ± 0.65 %ID/g) and was significantly reduced by pre-treatment with MC1 or celecoxib (1.62 ± 0.29 and 1.18 ± 0.21 %ID/g, respectively, p = 0.045 and p = 0.005). Radiometabolite analysis showed that [C]MC1 accounted for >90 % of tumor radioactivity, with <10 % in plasma, at 40 min post-injection of the radiotracer.Conclusions : [C]MC1 is a promising PET imaging agent for COX-2 in CRC and translation for cancer research should be considered.
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