Comparison of PSMA-HBED and PSMA-I and T as diagnostic agents in prostate carcinoma

Gallium(68)-labelled prostate-specific membrane antigen (PSMA) radiopharmaceuticals can be used to detect prostate cancer (PCa) cells due the their over expression of PSMA. The ⁶⁸Ga HBED-PSMA (PSMA-HBED) ligand has been most widely used and can be considered the current gold standard agent. Further PSMA ligands based on the DOTAGA and DOTA conjugates have more recently been developed. These agents (PSMA-I and T and PSMA-617) have potential theranostic capabilities as they can be conjugated with therapeutic radioisotopes. In this study, we examine whether PSMA-I and T has comparative efficacy, such that it could replace PSMA-HBED as a diagnostic agent in prostate carcinoma. 19 patients with PCa referred for ⁶⁸Ga-PSMA imaging were imaged with PSMA-HBED and PSMA-I and T PET-CT imaging within a 2-week period. The two pharmaceuticals were synthesised using click chemistry. Imaging was performed using the same standardised methodology on a Siemens Biograph mCT. All sites of PSMA binding thought to represent PCa (probable or definite) were included in a lesion analysis that examined lesion concordance and lesional binding efficiency (SUV_peak) between the two radiopharmaceuticals. For each patient, SUV_mean of the LV cavity blood pool, bone, muscle and liver were determined as image background measures. Across all patients, PSMA uptake was observed in 47 lesions (10 bone lesions, 19 nodal lesions, 18 high-grade intraprostatic binding). Lesions were concordant between the agents in all except for two small (<4 mm) nodal lesions which were not visualised with PSMA-I and T. SUV_peak assessment showed significantly greater overall lesion binding with HBED (paired t test, p = 0.0001). LV blood pool and bone marrow SUV_mean were significantly higher for I and T than HBED (paired t test, blood pool p < 1 x 10-5, bone marrow p < 0.005). Intra-patient comparative imaging demonstrates higher lesional PSMA-HBED binding than PSMA-I and T and that the HBED agent is likely to have better lesion contrast. While there was concordance in 96% of lesions, 2 small nodal lesions were appreciated with PSMA-HBED imaging while considered normal with PSMA-I and T. These findings suggest that HBED-PSMA has a slightly higher diagnostic accuracy in comparison to PSMA-I and T. (orig.)