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Updated: Jan 7, 2026
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Feasibility of albumin binding modulation in FAP-targeting radiopharmaceuticals: insights from molecular docking and
Sudabeh Shokrollahi1, Ahmad Amiri2
1Department of Chemistry, College of Science, University of Tehran, Tehran, 14155-6455, Iran.
Background:
Understanding the interaction between radiopharmaceuticals and human serum albumin (HSA) is essential for optimizing pharmacokinetics and therapeutic efficacy. This study evaluated the binding properties of natLu-FAPi-46 and natLu-FAP-2286 to HSA using theoretical and experimental techniques.
Results:
Docking results revealed moderate affinities for natLu-FAPi-46 (- 9.7 kcal/mol) and natLu-FAP-2286 (- 7.8 kcal/mol), correlating with their lower blood retention (0.43% and 0.03% I.A./g at 4 h p.i.). Comparative docking of albumin-binding derivatives of FAPi-46 showed stronger binding, consistent with increased blood retention. Experimental analyses (fluorescence quenching, circular dichroism, and cyclic voltammetry) confirmed complex formation and conformational changes in HSA, validating the computational findings.
Conclusions:
Together, the computational and experimental results underscore the importance of albumin-binding in shaping the pharmacokinetic properties of FAP-targeted radiopharmaceuticals. Strategic optimization of albumin-binding linkers may improve stability, circulation time, and overall therapeutic performance in next-generation FAP-based agents.
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