@article{discovery10183859, note = {{\copyright} 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).}, publisher = {MDPI AG}, month = {December}, journal = {Molecules}, year = {2023}, volume = {28}, number = {24}, title = {Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH)}, issn = {1420-3049}, keywords = {{{[}}18F]Fluoromethyl-(1,2-2H4)choline; positron emission tomography; choline; cell membrane metabolism; in vivo; in vitro; dosimetry; metastatic castrate-resistant prostate cancer}, abstract = {Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHK{\ensuremath{\alpha}}). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12-16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.}, author = {Challapalli, Amarnath and Barwick, Tara D and Dubash, Suraiya R and Inglese, Marianna and Grech-Sollars, Matthew and Kozlowski, Kasia and Tam, Henry and Patel, Neva H and Winkler, Mathias and Flohr, Penny and Saleem, Azeem and Bahl, Amit and Falconer, Alison and De Bono, Johann S and Aboagye, Eric O and Mangar, Stephen}, url = {https://doi.org/10.3390/molecules28248018} }