دورية أكاديمية
أعرض في EDS

Automated Radiosynthesis of [ 18 F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.

التفاصيل البيبلوغرافية
العنوان: Automated Radiosynthesis of [ 18 F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.
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: 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: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC11280013
DOI: 10.3390/ph17070833
PMID: 39065684
قاعدة البيانات: MEDLINE
الوصف
تدمد:1424-8247
DOI:10.3390/ph17070833