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Rational Design and Pharmacomodulation of 18 F-Labeled Biotin/FAPI-Conjugated Heterodimers.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2024 May 23; Vol. 67 (10), pp. 8361-8371. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
Abstract
- Due to the complex heterogeneity in different cancer types, the heterodimeric strategy has been intensively practiced to improve the effectiveness of tumor diagnostics. In this study, we developed a series of novel <superscript>18</superscript> F-labeled biotin/FAPI-conjugated heterobivalent radioligands ([ <superscript>18</superscript> F]AlF-NSFB, [ <superscript>18</superscript> F]AlF-NSFBP <subscript>2</subscript> , and [ <superscript>18</superscript> F]AlF-NSFBP <subscript>4</subscript> ), synergistically targeting both fibroblast activation protein (FAP) and biotin receptor (BR), to enhance specific tumor uptake and retention. The in vitro and in vivo biological properties of these dual-targeting tracers were evaluated, with a particular focus on positron emission tomography imaging in A549 and HT1080-FAP tumor-bearing mice. Notably, in comparison to the corresponding FAP-targeted monomer [ <superscript>18</superscript> F]AlF-NSF, biotin/FAPI-conjugated heterodimers exhibited a high uptake in tumor and prolong retention. In conclusion, as a proof-of-concept study, the findings validated the superiority of biotin/FAPI-conjugated heterodimers and the positive influence of biotin and linker on pharmacokinetics of radioligands. Within them, the bispecific [ <superscript>18</superscript> F]AlF-NSFBP <subscript>4</subscript> holds significant promise as a candidate for further clinical translational studies.
- Subjects :
- Animals
Humans
Mice
Drug Design
Radiopharmaceuticals chemistry
Radiopharmaceuticals pharmacokinetics
Radiopharmaceuticals chemical synthesis
Radiopharmaceuticals pharmacology
Positron-Emission Tomography
Mice, Nude
Tissue Distribution
Dimerization
Cell Line, Tumor
Mice, Inbred BALB C
Fluorine Radioisotopes chemistry
Biotin chemistry
Biotin pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 67
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38726551
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.4c00544