Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH).
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Embargo End Date
ICR Authors
Authors
Challapalli, A
Barwick, TD
Dubash, SR
Inglese, M
Grech-Sollars, M
Kozlowski, K
Tam, H
Patel, NH
Winkler, M
Flohr, P
Saleem, A
Bahl, A
Falconer, A
De Bono, JS
Aboagye, EO
Mangar, S
Barwick, TD
Dubash, SR
Inglese, M
Grech-Sollars, M
Kozlowski, K
Tam, H
Patel, NH
Winkler, M
Flohr, P
Saleem, A
Bahl, A
Falconer, A
De Bono, JS
Aboagye, EO
Mangar, S
Document Type
Journal Article
Date
2023-12-08
Date Accepted
2023-12-06
Abstract
Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). 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.
Citation
Molecules, 2023, 28 (24), pp. 8018 -
Source Title
Molecules
Publisher
MDPI
ISSN
1420-3049
eISSN
1420-3049
Collections
Research Team
PrCa Targeted Therapy