In:
Lab on a Chip, Royal Society of Chemistry (RSC)
Abstract:
Copper-mediated radiofluorination has demonstrated remarkable potential in forming aromatic C- 18 F bonds of radioligands for positron emission tomography (PET). Achieving optimal results often requires optimization efforts, requiring 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 [ 18 F]FDOPA as an illustrative example. In our current work, we optimized the Cu-mediated synthesis of a novel monoacylglycerol lipase (MAGL) PET tracer ([ 18 F]YH149), showing 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), using 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). The successful translation to vial-based reactions ensures wider applicability of the optimized synthesis by leveraging widely available commercial vial-based synthesis modules.
Type of Medium:
Online Resource
ISSN:
1473-0197
,
1473-0189
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2023
detail.hit.zdb_id:
2056646-3
SSG:
12
Permalink