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

Abstract

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.

Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents

“…53 This effect correlated with decreased ChoK expression thus indicating that the reduction in PC previously reported with 31 …”

“…Interestingly, a reduction in cellular PC content and ChoK activity is also observed with the MEK inhibitors U0126 52 and PD059001 53 and following FASN inhibition with orlistat and cerulenin, 71 suggesting a degree of regulatory overlap between proteins such as PI3K, MEK and FASN over PC homeostasis. This is perhaps unsurprising given the multiplicity of cellular Furthermore, a decline in levels of PC and PtdCho detected by 1 H, 31 P and 13 C MRS was also observed that was linked to ChoK inhibition.…”

Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

“…Because of the metabolic instability of choline radiotracers and the desire to use late imaging protocols (;60 min, to permit elimination of nonspecific metabolites), we developed a more stable choline radiotracer, 18 F-D4-FCH (12). A series of preclinical studies showed that the new tracer has improved protection against oxidation by choline oxidase, the key choline catabolic enzyme, via a 1 H/ 2 D isotope effect, together with fluorine substitution (12,14,15). The objective of this study was to investigate the biodistribution and dosimetry in human subjects and extend pharmacokinetic aspects of the preclinical findings into human application.…”

“…1). The simple substitution of deuterium ( 2 D) for hydrogen ( 1 H) and the presence of 18 F improve the stability of the compound and reduce degradation of the parent tracer (12,14,15). This modification is hypothesized to increase the net availability of the parent tracer for phosphorylation and trapping within cells, leading to a better signal-to-background contrast, thus improving tumor detection sensitivity of PET.…”

“…18 F-D4-FCH has been validated for imaging tumors preclinically and was found to be a promising, metabolically stable radiotracer for imaging choline metabolism in tumors (14,15). To our knowledge, we present the first human study of 18 F-D4-FCH, performed on healthy volunteers, to evaluate the dosimetry, biodistribution, and safety of this radiotracer.…”