Amanda J Boyle1, Andrea Narvaez2, Junchao Tong2, Sami S Zoghbi3, Victor W Pike3, Robert B Innis3, Neil Vasdev4,5. 1. Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. amy.boyle@camh.ca. 2. Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. 3. National Institute of Mental Health, Bethesda, MD, USA. 4. Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. neil.vasdev@utoronto.ca. 5. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. neil.vasdev@utoronto.ca.
Abstract
PURPOSE: Cyclooxygenase-2 (COX-2) is a target for inflammation and colorectal cancer (CRC). This study evaluated the COX-2 neuro-PET radiopharmaceutical, [11C]MC1, in CRC xenograft mice. PROCEDURES: [11C]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 [11C]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 [11C]MC1 accounted for >90 % of tumor radioactivity, with <10 % in plasma, at 40 min post-injection of the radiotracer. CONCLUSIONS: [11C]MC1 is a promising PET imaging agent for COX-2 in CRC and translation for cancer research should be considered.
PURPOSE: Cyclooxygenase-2 (COX-2) is a target for inflammation and colorectal cancer (CRC). This study evaluated the COX-2 neuro-PET radiopharmaceutical, [11C]MC1, in CRC xenograft mice. PROCEDURES: [11C]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 [11C]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 [11C]MC1 accounted for >90 % of tumor radioactivity, with <10 % in plasma, at 40 min post-injection of the radiotracer. CONCLUSIONS: [11C]MC1 is a promising PET imaging agent for COX-2 in CRC and translation for cancer research should be considered.
Authors: Kimmie Ng; Jeffrey A Meyerhardt; Andrew T Chan; Kaori Sato; Jennifer A Chan; Donna Niedzwiecki; Leonard B Saltz; Robert J Mayer; Al B Benson; Paul L Schaefer; Renaud Whittom; Alexander Hantel; Richard M Goldberg; Alan P Venook; Shuji Ogino; Edward L Giovannucci; Charles S Fuchs Journal: J Natl Cancer Inst Date: 2014-11-27 Impact factor: 13.506
Authors: Stefanie Meyer; Thomas Vogt; Michael Landthaler; Anna Berand; Albrecht Reichle; Frauke Bataille; Andreas H Marx; Anne Menz; Arndt Hartmann; Leoni A Kunz-Schughart; Peter J Wild Journal: PPAR Res Date: 2009-07-20 Impact factor: 4.964