In Silico Investigation of the Interactions of Piflufolastat F-18 and Flotufolastat F-18 Radiopharmaceuticals with Biological Targets Relevant to Prostate Cancer Diagnosis
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Prostate cancer is one of the major public health concerns among men worldwide. Early and accurate diagnosis remains a significant challenge, particularly for the detection of small-volume lesions and early recurrences. Positron emission tomography (PET) imaging using radiopharmaceuticals targeting the Prostate-Specific Membrane Antigen (PSMA) has considerably improved diagnostic management. In this study, an in silico molecular modeling approach was employed to analyze and compare the interactions between two fluorine-18–labeled radiopharmaceuticals, Piflufolastat F-18 and Flotufolastat F-18, and several biological targets involved in prostate cancer, including the androgen receptor (AR), HIF-1α, HER2, and PSMA. Molecular docking was used to evaluate binding affinities and to identify stabilizing interactions at the atomic level. The results show that both radiopharmaceuticals exhibit strong affinity for PSMA, with particularly favorable binding energies, confirming their relevance in diagnostic imaging. Furthermore, Piflufolastat F-18 behaves as a multi-target ligand, which may reduce its selectivity, whereas Flotufolastat F-18 appears highly selective This study highlights the value of molecular modeling as a complementary tool for understanding ligand–receptor interactions and for the future optimization of PSMA-targeted radiotracers.
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