Toward harmonized PROMISE PSMA scoring: a simple approach for correcting 18F-PSMA-1007 liver uptake based on 68Ga-PSMA-11 and 18F-DCFPyL reference values

The PROMISE framework standardizes PSMA PET interpretation using reference organs, particularly the liver. For hepatobiliary-excreted tracers (e.g., 18 F-PSMA-1007), the spleen was proposed as an alternative reference, though without quantitative validation. We evaluated PSMA-ligand uptake patterns among 18 F-PSMA-1007, 68 Ga-PSMA-11, and 18 F-DCFPyL to assess the validity of spleen-based referencing and develop a simple approach that may harmonize 18 F-PSMA-1007 liver uptake with that of renally-excreted tracers. 331 consecutive PSMA PET-CT studies (n = 118/95/118 for 68 Ga-PSMA-11/ 18 F-PSMA-1007/ 18 F-DCFPyL) were analyzed: SUVs were retrospectively measured in all studies in reference tissues (blood pool, liver, parotid), with SUV spleen also recorded for 18 F-PSMA-1007. SUV liver differed markedly across tracers: 18 F-PSMA-1007 (13.95 ± 4.71) > 68 Ga-PSMA-11 (7.45 ± 4.59) ≈ 18 F-DCFPyL (8.11 ± 1.78), p < 0.01. The elevated 18 F-PSMA-1007 liver uptake expanded the PROMISE score-1 range (SUV range between SUV blood pool and SUV liver ) and compressed that of score-2 (SUV range between SUV liver and SUV parotid ). SUV spleen in this group (12.24 ± 5.67) showed only moderate correlation with SUV liver ( r = 0.43) and exceeded SUV liver in 29% of cases, questioning the utility of spleen uptake as a consistent alternative to liver uptake-based cutoff. Linear correction using the inverse ratio of mean SUV liver ( 18 F-PSMA-1007 versus other tracers; factor = 0.56, 95% CI 0.51–0.61) yielded SUV liver-corrected of 7.8 ± 2.63 in the 18 F-PSMA-1007 group. Applying SUV spleen as a PSMA score 1–2 cutoff failed to resolve score distribution imbalance, upstaging only 11.8% of score-1 lesions to score-2. By contrast, the use of SUV liver-corrected (SUV liver × 0.56) as this cutoff harmonized the score distribution in the 18 F-PSMA-1007 cohort relative to 68 Ga-PSMA-11 and 18 F-DCFPyL, leading to reclassification of 38.2% of score-1 lesions as score-2. In PET with 18 F-PSMA-1007, PROMISE scoring based on unadjusted liver or spleen uptake systematically underestimates lesion scores. The simple linear correction approach proposed here offers a research avenue for enhancing the consistency of PSMA scoring for improved interpretive standardization. This study contains data obtained from a prospective Registry Trial: ClinicalTrials.gov, NCT03718260, registered October 24, 2018.