A59
Development of a deuterium choline analogue radiotracer [18F]Fluoromethyl-[1,2-2H4]-choline for cancer imaging
Julius Leyton1, Graham Smith1, Yongjun Zhao1, Meg Perumal1, Quang-De Nguyen1, Edward Robins2, Erik rstad2, Eric O. Aboagye1
1Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, London, UK, 2MDx Discovery (part of GE Healthcare) at Hammersmith Imanet Ltd., London, UK
Current radiotracers for positron emission tomography (PET) imaging of choline metabolism have poor systemic metabolic stability in vivo. We have developed [18F]fluoromethyl-[1,2-2H4]-choline (D4-FCH), that employs deuterium isotope effect to improve metabolic stability of radiotracer choline. D4-FCH proved more resistant to oxidation than its non-deuterated analog, [18F]fluoromethylcholine (FCH), in plasma, kidneys, liver and tumour, while retaining phosphorylation potential. Tumour radiotracer levels, a determinant of sensitivity in imaging studies, was improved by deuterium substitution; tumour uptake values expressed as %injected dose/voxel at 60 min were 7.43 0.47 and 5.50 0.49 for D4-FCH and FCH, respectively, (P = 0.04). D4-FCH was also found to be a useful response biomarker. Treatment with the mitogenic extracellular kinase inhibitor, PD0325901, resulted in a reduction in tumour radiotracer uptake that occurred in parallel with reductions choline kinase A expression. In conclusion, D4-FCH is a very promising metabolically stable radiotracer for imaging choline metabolism in tumours.
