RPS COMMUNITY OF PRACTICE: Development of [18F]-4-Fluorohomoleucine as a Novel PET Tracer for Cancer Imaging

Development of [18F]-4-Fluorohomoleucine as a Novel PET Tracer for Cancer Imaging

Dr Marzieh Ahangarpour will be presenting the RPS COP lecture for August 2026. Join online via Microsoft Teams with the event location link.

Meeting ID: 438 981 196 022 514
Passcode: E9YK3wk2

Abstract

Positron emission tomography (PET) is an established imaging modality used for the early detection of tumours and metastases and plays an important role in the diagnosis, staging and treatment planning of many malignancies. Although the glucose analogue [18F]FDG is widely used for tumour imaging, its performance in the brain and in some solid tumours can be limited by high physiological background uptake and poor tumour-to-background contrast. One promising alternative is the use of 18F-labelled amino acids, which exploit the upregulation of amino acid transport in malignant cells. Among these transport systems, L-type amino acid transporters, particularly LAT1, have emerged as attractive molecular targets because of their increased expression in many tumours relative to normal tissues. The LAT1-targeted PET tracer 4-[18F]fluorohomoleucine ([18F]FHL) is a branched-chain amino acid analogue that is stable in vivo, selectively probes LAT1-mediated amino acid transport, shows rapid tumour uptake and exhibits minimal bone uptake. In several preclinical cancer models, including glioblastoma, prostate cancer and multiple myeloma, [18F]FHL demonstrated favourable imaging performance compared with [18F]FDG, including high tumour uptake, strong tumour-to-background contrast and improved delineation of tumour margins.
The original radiosynthetic route to [18F]FHL relied on electrophilic [18F]F2 gas, limiting molar activity and restricting production to specialised facilities. To overcome these limitations, we investigated a nucleophilic approach using [18F]fluoride to improve both molar activity and accessibility. Although selective nucleophilic fluorination of tertiary alkyl centres has been reported in organic and medicinal chemistry, its scope remains limited, particularly in fluorine-18 radiochemistry. We developed a new nucleophilic radiofluorination approach for the late-stage incorporation of fluorine-18 into unactivated tertiary alkyl bromides using [18F]AgF. This strategy provides a robust and operationally practical route to [18F]FHL, enabling scalable production, simplified purification and the further development of LAT1-targeted PET imaging agents towards clinical translation.

Biography

Dr Marzieh Ahangarpour is a radiopharmaceutical scientist with a background in bioconjugate chemistry. She completed her PhD in Chemistry at the University of Auckland, New Zealand, and subsequently conducted postdoctoral research there in peptide and protein modification and antibody–drug conjugates for targeted cancer therapy. Building on this background, she moved into radiochemistry and joined Simon Fraser University and TRIUMF, Canada’s particle accelerator centre, as a postdoctoral researcher developing new radiolabeling methods for PET radiotracers in cancer imaging.