Repurposing [11C]MC1 for PET Imaging of Cyclooxygenase-2 in Colorectal Cancer Xenograft Mouse Models

Abstract

Cyclooxygenase-2 (COX-2) is a target for inflammation and colorectal cancer (CRC). This study evaluated the COX-2 neuro-PET radiopharmaceutical, [ 11 C]MC1, in CRC xenograft mice. Procedures: [ 11 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 [ 11 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 [ 11 C]MC1 accounted for >90 % of tumor radioactivity, with <10 % in plasma, at 40 min post-injection of the radiotracer. Conclusions: [ 11 C]MC1 is a promising PET imaging agent for COX-2 in CRC and translation for cancer research should be considered.

Strategies for designing novel positron emission tomography (PET) radiotracers to cross the blood–brain barrier

“…Unfortunately, BBB-permeable radiometabolites of [ 11 C]OCM-44 were observed in NHPs and mice. 112,115 The lead 18 F-labeled analog, [ 18 F]OCM-50 (Figure 6), demonstrated peak SUV 2.0 in both Sprague-Dawley rats and NHPs. 113 Our recent F I G U R E 6 Structures of GSK-3 PET radiotracers showing improved BBB permeability with minor structural modifications.…”

“…113 Our recent F I G U R E 6 Structures of GSK-3 PET radiotracers showing improved BBB permeability with minor structural modifications. [110][111][112][113] Abbreviations: BBB, blood-brain barrier; GSK-3, glycogen synthase kinase-3; PET, positron emission tomography.…”

“…We proceeded to develop second generation radiotracers for GSK‐3 based on PF‐367, and the highest brain uptake was observed with [ 11 C]OCM‐44 (Figure 6), which displayed a three‐fold increase in peak NHP brain uptake compared with [ 11 C]PF‐367. Unfortunately, BBB‐permeable radiometabolites of [ 11 C]OCM‐44 were observed in NHPs and mice 112,115 . The lead 18 F‐labeled analog, [ 18 F]OCM‐50 (Figure 6), demonstrated peak SUV 2.0 in both Sprague‐Dawley rats and NHPs 113 .…”