PET/CT With ⁶⁸Ga-PSMA in Prostate Cancer: Radiopharmaceutical Background and Clinical Implications

Background and objective: In the last twenty years, positron emission tomography / computed tomography (PET/CT) with radiolabeled choline, represented the most powerful imaging modality for prostate cancer (PCa). However, the low positive detection rate of the technique for PSA < 1 ng/ml prompted the development of other tracers for imaging PCa. Methods: We performed a critical review of ⁶⁸Ga-PSMA, a receptor ligand tracer, which has been identified as the most promising radiopharmaceutical for imaging PCa. Results: The most promising feature of this radiopharmaceutical is the high positive detection rate for prostate specific antigen (PSA) levels < 1 ng/ml or less (i.e., PSA < 0.5 ng/ml). ⁶⁸Ga-PSMA detection rate is also sensitive to PSA kinetics, expressed either as PSA doubling time or PSA velocity. There are initial results indicating that ⁶⁸Ga-PSMA may significantly affect the clinical management of PCa patients, even though the additional advantages in comparison to radiolabeled choline need to be further supported in future perspective studies. Other clinical implications, such as whether ⁶⁸Ga-PSMA PET/CT predicts PCa-specific survival, have not yet been investigated. Numerous clinical studies have been published, some of them with histopathological verification so that despite the recent introduction in the clinical field reliable estimation of sensitivity and specificity of ⁶⁸Ga-PSMA PET/CT have been obtained through meta-analyses. Most clinical studies with PET/CT with ⁶⁸Ga-PSMA are retrospective, single-institutional studies and in many cases include heterogeneous patient cohorts. Thus, multidisciplinary, well-throughout prospective trials are needed to better define the clinical implications of ⁶⁸Ga- PSMA PET/CT in PCa patients. The increasing availability of positron emission tomography / magnetic resonance (PET/MR) hybrid devices promotes the use of this radiopharmaceutical especially at initial staging when identification of tumor localization and of extra-prostatic disease represent clinically relevant questions. PSMA cold ligands can also be labeled with beta emitters with good chemical stability so that ⁶⁸Ga-PSMA PET/CT can be used to guide radiometabolic therapy of advanced metastatic PCa patients through ¹⁷⁷Lu-labeled PSMA ligands. Conclusion: PSMA labeled ligands appear very promising for diagnosis and treatment of PCa.