| Summary: | Background: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. Methods: the research investigates PSMA expression in vivo among TNBC patients using [<sup>18</sup>F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [<sup>18</sup>F]FDG PET/CT. Results: The study involves 10 TNBC patients, revealing comparable uptake of [<sup>18</sup>F]PSMA-1007 and [<sup>18</sup>F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUV<sub>max</sub> values in both modalities. Two patients had uncountable lung metastases positive in both [<sup>18</sup>F]FDG and [<sup>18</sup>F]PSMA-1007 scans. PET-positive bone metastases were identified by <sup>18</sup>F-PSMA in four patients, while elevated [<sup>18</sup>F]FDG uptake was found only in three of them. Distant metastases displayed higher SUV<sub>max</sub> values in the [<sup>18</sup>F]PSMA-1007 PET/CT, as compared to [<sup>18</sup>F]FDG. Additionally, brain metastases were exclusively detected using [<sup>18</sup>F]PSMA-1007. Conclusions: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [<sup>18</sup>F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype.
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