Background <p>Triple-negative breast cancer (TNBC) is an aggressive molecular subtype of breast cancer with limited treatment approaches. Prostate-specific membrane antigen (PSMA), widely applied as a target for molecular imaging and radioligand therapy of prostate cancer, demonstrates the highest expression in TNBC across all molecular subtypes of breast cancer, and represents a promising target for imaging and treatment of TNBC patients.</p> Methods <p>This prospective study included 20 patients with metastatic TNBC who underwent both [¹⁸F]PSMA-1007 and [¹⁸F]FDG PET/CT. Qualitative and quantitative image analysis was performed to determine the uptake predominance of one of the tracers and the added value of the diagnostic CT, as well as to assess the potential applicability of PSMA-targeted radioligand therapy (PSMA-RLT).</p> Results <p>A total of 229 lesions were identified using both [¹⁸F]PSMA-1007 and [¹⁸F]FDG PET/CT. Concordant and discordant lesions were observed for both tracers, with a greater number of discordant lesions identified by [¹⁸F]PSMA-1007. [¹⁸F]FDG demonstrated higher uptake in TNBC lesions. An exception was observed in lung lesions, where no significant difference was found between tracers. The application of diagnostic CT revealed additional TNBC lesions that were not identified by PET, for each tracer. None of the patients demonstrated a [¹⁸F]PSMA-1007 uptake level sufficient for potential PSMA-RLT application when a lesional SUV-based threshold was used.</p> Conclusion <p>Despite detectable [¹⁸F]PSMA-1007 uptake in TNBC lesions, [¹⁸F]FDG uptake was generally higher. Furthermore, the diagnostic CT can identify additional PET-negative lesions. Although PSMA expression is confirmed in TNBC, it may be insufficient to provide potential benefit from PSMA-RLT for this patient group.</p>