Fully automated [¹⁸F]AlF radiolabeling using a microdroplet reactor platform
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
The preparation of ¹⁸F-labeled biomolecules for PET imaging is often challenging due to complex synthesis protocols and the short half-life of F-18 (109.8 min). The aluminum-[¹⁸F]fluoride ([18F]AlF) method offers a straightforward, efficient route for radiofluorinating biomolecules, with demonstrated utility in both preclinical and clinical imaging. However, one flaw in this technique is the mismatch between the typical microvolume conditions required for high-yield [18F]AlF chelation and the milliliter-scale operation of commercial automated radiosynthesizers. To address this shortcoming, we leverage microscale radiochemistry techniques and report the first fully-automated, droplet-based production of [¹⁸F]AlF-labeled compounds using a compact and cost-effective platform. The optimized process was first achieved using a NODA analogue (NODA-Tz) as a model substrate at a 15 μL reaction scale, and was subsequently applied to the fully automated synthesis of the clinically-relevant PET probe [¹⁸F]AlF-FAPI-74 which targets fibroblast activation protein expressed in most cancers. [¹⁸F]AlF-FAPI-74 (n = 3) was obtained with high radiochemical yield (RCY, 75 ± 5 %), radiochemical purity (RCP, >99 %), activity yield (67 ± 4 %), and apparent molar activity (Am, 358–482 GBq/μmol). Starting from 2.6 to 3.5 GBq of [18F]fluoride, the final product quantity (1.8–2.4 GBq) was sufficient for multiple patient doses. Compared to the conventional vial-based methods, the microdroplet approach showed significant improvements including reduced synthesis time (19 ± 1 min vs. 31 min), higher yield, and reduced precursor consumption (5 nmol vs. 80 nmol). This work demonstrates the feasibility and advantages of translating [¹⁸F]AlF chemistry to a microdroplet platform, enabling more efficient radiotracer production and broader clinical accessibility.
Date Issued
2026-01-15
Date Acceptance
2025-12-29
Citation
Chemical Engineering Journal, 2026, 528
ISSN
1385-8947
Publisher
Elsevier BV
Journal / Book Title
Chemical Engineering Journal
Volume
528
Copyright Statement
Copyright © 2026 Elsevier B.V. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Publication Status
Published
Article Number
172440
Date Publish Online
2026-01-06