n-n-dimethyl-n-(18f)fluoromethyl-2-hydroxyethylammonium and Melanoma

Topics: Adenocarcinoma; Choline; Humans; Male; Melanoma; Meningeal Carcinomatosis; Middle Aged; Neoplasms, Multiple Primary; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms

Current radiotracers for positron emission tomography imaging of choline metabolism have poor systemic metabolic stability in vivo. We describe a novel radiotracer, [(18)F]fluoromethyl-[1,2-(2)H(4)]-choline (D4-FCH), that employs deuterium isotope effect to improve metabolic stability. D4-FCH proved more resistant to oxidation than its nondeuterated analogue, [(18)F]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 [(18)F]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.

Topics: Animals; Benzamides; Choline; Colonic Neoplasms; Deuterium; Diphenylamine; HCT116 Cells; Humans; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Oxidation-Reduction; Positron-Emission Tomography; Radiopharmaceuticals; Tissue Distribution; Transplantation, Heterologous