Issue 21, 2023

Proof-of-concept optimization of a copper-mediated 18F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Abstract

Copper-mediated radiofluorination has demonstrated remarkable potential in forming aromatic C–18F bonds of radioligands for positron emission tomography (PET). Achieving optimal results often requires optimization efforts, requiring a substantial amount of radiolabeling precursor and time, severely limiting the experimental throughput. Recently, we successfully showcased the feasibility of performing and optimizing Cu-mediated radiosynthesis on a high-throughput microdroplet platform using the well-known and clinically used radioligand [18F]FDOPA as an illustrative example. In our current work, we optimized the Cu-mediated synthesis of a novel monoacylglycerol lipase (MAGL) PET tracer ([18F]YH149), showing the versatility of droplet-based techniques for early stage tracer development. Across 5 days, we conducted a total of 117 experiments, studying 36 distinct conditions, while utilizing <15 mg of total organoboron precursor. Compared to the original report in which the radiochemical yield (RCY) was 4.4 ± 0.5% (n = 5), the optimized droplet condition provided a substantial improvement in RCY (52 ± 8%, n = 4) and showed excellent radiochemical purity (100%) and molar activity (77–854 GBq μmol−1), using a starting activity of 0.2–1.45 GBq. Furthermore, we showed for the first time a translation of the optimized microscale conditions to a vial-based method. With similar starting activity (0.2–1.44 GBq), the translated synthesis exhibited a comparable RCY of 50 ± 10% (n = 4) while maintaining excellent radiochemical purity (100%) and acceptable molar activity (20–46 GBq μmol−1). The successful translation to vial-based reactions ensures wider applicability of the optimized synthesis by leveraging widely available commercial vial-based synthesis modules.

Graphical abstract: Proof-of-concept optimization of a copper-mediated 18F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Supplementary files

Article information

Article type
Paper
Submitted
27 ኦገስ 2023
Accepted
27 ሴፕቴ 2023
First published
02 ኦክቶ 2023

Lab Chip, 2023,23, 4652-4663

Proof-of-concept optimization of a copper-mediated 18F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Y. Lu, Y. He, R. Schibli, L. Mu and R. M. van Dam, Lab Chip, 2023, 23, 4652 DOI: 10.1039/D3LC00735A

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