دورية أكاديمية
Automated Radiosynthesis of [ 18 F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.
العنوان: | Automated Radiosynthesis of [ 18 F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation. |
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المؤلفون: | Witek JA; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Brooks AF; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Kapila SM; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA., Winton WP; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Stauff JR; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Scott PJH; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.; The Interdepartmental Program in Medicinal Chemistry, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA., Viglianti BL; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. |
المصدر: | Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 Jun 25; Vol. 17 (7). Date of Electronic Publication: 2024 Jun 25. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101238453 Publication Model: Electronic Cited Medium: Print ISSN: 1424-8247 (Print) Linking ISSN: 14248247 NLM ISO Abbreviation: Pharmaceuticals (Basel) Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, c2004- |
مستخلص: | 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. |
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معلومات مُعتمدة: | R01 EB021155 United States EB NIBIB NIH HHS; 2023 NETRF Investigator Award 23-PAF08146 Neuroendocrine Tumor Research Foundation |
فهرسة مساهمة: | Keywords: FAPI; cancer-associated fibroblast; fibroblast activation protein; radioflourination |
تواريخ الأحداث: | Date Created: 20240727 Latest Revision: 20240822 |
رمز التحديث: | 20240822 |
مُعرف محوري في PubMed: | PMC11280013 |
DOI: | 10.3390/ph17070833 |
PMID: | 39065684 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1424-8247 |
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DOI: | 10.3390/ph17070833 |