The Homunculus of unspecific bone uptakes associated with PSMA-targeted tracers: a systematic review-based definition

Purpose: Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior diagnostic accuracy over traditional methods and enabling theragnostic applications. However, a significant diagnostic challenge has emerged with identifying unspecific bone uptakes (UBUs), which could lead to over-staging and inappropriate treatment decisions if misinterpreted. This systematic review explores the phenomenon of UBUs in PCa patients undergoing PSMA-PET imaging.

Methods: Studies assessing the prevalence, topographical distribution, and potential clinical implications of UBUs were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.

Results: The percentage of PCa patients with UBUs on PSMA-PET scans ranged from 0 to 71.7%, depending on the radiopharmaceutical used, with [¹⁸F]PSMA-1007 showing the highest incidence. The ribs are the primary site of UBUs across all PSMA-targeted radiopharmaceuticals. The spine is the second most frequent UBU site for [⁶⁸Ga]Ga-PSMA-11, [¹⁸F]DCFPyL, [¹⁸F]rhPSMA-7, while the pelvic girdle represents the second most frequent site for [¹⁸F]PSMA-1007. The average maximum Standardized Uptake Value (SUV_max) of UBUs varied from 3.4 to 7.7 and was generally lower than that of bone metastases.

Conclusions: Our findings underscore the need for heightened awareness and precise interpretation of UBUs to avoid potential over-staging and subsequent inappropriate treatment decisions. Considering the radiopharmaceutical used, PET-derived semiquantitative parameters, the topographical distribution of UBUs, and accurately evaluating the pre-test probability based on clinical and laboratory parameters may aid nuclear medicine physicians in interpreting PSMA-PET findings.