Effect of 18F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial

Abstract

on behalf of the FALCON study group

18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy

“…The personalised information obtained can guide management decisions as well as support the design of future trials focussing on prostate cancer patients with the earliest signs of tumour resistance to ADT, prior to clinical evidence of cancer recurrence judged by PSA testing. Active transport of synthetic L-leucine analogues such as 18 F labelled 1-amino-3-fluorocyclobutane-1-carboxylic acid (or 18 F-Fluciclovine or 18 F-FACBC) into cells is thought to be mediated by L-type neutral amino acid transporter 1 (LAT1) and alanine-serine-cysteine-transporter (ASCT2) [5,6]. LAT1 is a sodium independent exchange amino acid transporter (AAT) between intracellular and extracellular environments [7].…”

“…In contrast, ASCT2 mediates amino acid uptake in a sodium-dependent manner [7,8]. As a leucine analogue, 18 F-Fluciclovine is not incorporated into proteins, but its uptake mirrors that of glutamine [6,9], which plays a key role in cancer metabolism [7]. As both LAT1 and ASCT2 have been detected in prostate cancer cells, 18 F-Fluciclovine is a promising PET radiotracer for functional prostate cancer imaging.…”

“…As a leucine analogue, 18 F-Fluciclovine is not incorporated into proteins, but its uptake mirrors that of glutamine [6,9], which plays a key role in cancer metabolism [7]. As both LAT1 and ASCT2 have been detected in prostate cancer cells, 18 F-Fluciclovine is a promising PET radiotracer for functional prostate cancer imaging. 18 F-Fluciclovine is already approved by the European Medicines Agency in Europe [10] and the Food and Drug Administration in the USA [11] for diagnostic imaging in prostate cancer sufferers with biochemical evidence of cancer recurrence.…”

“…As both LAT1 and ASCT2 have been detected in prostate cancer cells, 18 F-Fluciclovine is a promising PET radiotracer for functional prostate cancer imaging. 18 F-Fluciclovine is already approved by the European Medicines Agency in Europe [10] and the Food and Drug Administration in the USA [11] for diagnostic imaging in prostate cancer sufferers with biochemical evidence of cancer recurrence. Favourable cancer detection performance for 18 F-Fluciclovine PET imaging has been reported across a wide range of PSA values [12,13].…”

“…We hypothesise that castration-resistant prostate cancer has a distinct profile of AATs expression that alters the tumoral 18 F-Fluciclovine uptake. We applied acute and chronic ADT (in CWR22Res and 22Rv1 orthografts, respectively) as tools to mimic early and established castrationresistant disease and performed longitudinal (matched) 18 F-Fluciclovine PET/MRI scans.…”