1. Automated Radiosynthesis of [ 18 F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.
- Author
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Witek, Jason A., Brooks, Allen F., Kapila, Sahil M., Winton, Wade P., Stauff, Jenelle R., Scott, Peter J. H., and Viglianti, Benjamin L.
- Subjects
RADIATION dosimetry ,SMALL molecules ,FIBROBLASTS ,RADIOISOTOPES ,TIN - Abstract
Background: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy. All currently used FAPI rely on a linker–chelator complex attached to the 'inhibitor'. We describe a new automated method of the direct attachment of the radioisotope to the inhibitor, resulting in a >50% MW reduction with the hope of an improved tumor-to-background ratio and tumor uptake. Methods: [
18 F]FluroFAPI was developed from a Sn precursor. This allowed for subsequent automated radioflourination. We obtained the biodistribution of [18 F]FluroFAPI in rats, performed estimated human radiation dosimetry, and performed a 100× expected single dose toxicology analysis for eventual first-in-human experiments. Results: The synthesis of the Sn precursor for FluorFAPI and the automated synthesis of [18 F]FluroFAPI was demonstrated. [18 F]FluroFAPI had favorable estimated human radiation dosimetry, and demonstrated no adverse effects when injected at a dose of 100× that planned for [18 F]FluroFAPI. Conclusions: With the successful development of an automated synthesis of [18 F]FluroFAPI, first-in-human testing can be planned with the hope of an improved tumor-to-background performance compared to other FAPI agents. [ABSTRACT FROM AUTHOR]- Published
- 2024
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