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[¹⁸F]Fluoromethyl-[1,2-²H₄]-Choline: A Novel Radiotracer for Imaging Choline Metabolism in Tumors by Positron Emission Tomography

¹ Molecular Therapy Group, Faculty of Medicine, Imperial College London; ² MDx Discovery (part of GE Healthcare) at Hammersmith Imanet Ltd., Hammersmith Hospital, London, United Kingdom

Requests for reprints: Eric O. Aboagye, Molecular Therapy Group, Faculty of Medicine, Imperial College London, Room 240, MRC Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom. Phone: 44-2083833759; Fax: 44-2083831783; E-mail: eric.aboagye{at}imperial.ac.uk.

Key Words: [¹⁸F]Fluoromethyl-[1,2-²H₄]-choline • positron emission tomography • imaging • choline metabolism • therapy response

Current radiotracers for positron emission tomography imaging of choline metabolism have poor systemic metabolic stability in vivo. We describe a novel radiotracer, [¹⁸F]fluoromethyl-[1,2-²H₄]-choline (D4-FCH), that employs deuterium isotope effect to improve metabolic stability. D4-FCH proved more resistant to oxidation than its nondeuterated analogue, [¹⁸F]fluoromethylcholine, in plasma, kidneys, liver, and tumor, while retaining phosphorylation potential. Tumor radiotracer levels, a determinant of sensitivity in imaging studies, were improved by deuterium substitution; tumor uptake values expressed as percent injected dose per voxel at 60 min were 7.43 ± 0.47 and 5.50 ± 0.49 for D4-FCH and [¹⁸F]fluoromethylcholine, 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 tumor radiotracer uptake that occurred in parallel with reductions in choline kinase A expression. In conclusion, D4-FCH is a very promising metabolically stable radiotracer for imaging choline metabolism in tumors. [Cancer Res 2009;69(19):7721–8]