Eligibility for (177)Lu-PSMA Therapy Depends on the Choice of Companion Diagnostic Tracer: A Comparison of (68)Ga-PSMA-11 and (99m)Tc-MIP-1404 in Metastatic Castration-Resistant Prostate Cancer

(177)Lu-prostate-specific membrane antigen-617 ((177)Lu-PSMA-617) is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC), with evidence of improved survival over standard care. The VISION trial inclusion criteria required a metastatic lesion-to-liver ratio of greater than 1 on (68)Ga-PSMA-11 PET scans. We aimed to determine whether an equivalent ratio is suitable for a SPECT tracer, (99m)Tc-MIP-1404, and to compare lesion and lesion–to–normal-organ ratios between the 2 radiotracers. Methods: Two cohorts of patients with mCRPC matched for age, prostate-specific antigen level, and total Gleason score, with either (99m)Tc-MIP-1404 SPECT/CT (n = 25) or (68)Ga-PSMA-11 PET/CT (n = 25) scans, were included for analysis. Up to 3 lesions in each site (prostate/prostate bed, lymph nodes, bone and soft-tissue metastases) as well as normal liver, parotid gland, spleen, and mediastinal blood-pool SUV(max) were measured. Results: (99m)Tc-MIP-1404 SPECT lesion SUV(max) was not significantly different from (68)Ga-PSMA-11 PET (median, 18.2 vs. 17.3; P = 0.93). However, (99m)Tc-MIP-1404 liver SUV(max) was higher (median, 8.5 vs. 5.8; P = 0.002) and lesion-to-liver ratios were lower (median, 2.7 vs. 3.5; P = 0.009). There was no significant difference in parotid gland or splenic SUV(max) or lesion–to–parotid gland ratios between the 2 tracers although there was a small difference in lesion-to-spleen ratios (P = 0.034). Conclusion: There are differences in biodistribution and, in particular, liver activity, between (68)Ga-PSMA-11 and (99m)Tc-MIP-1404. Therefore, if (99m)Tc-MIP-1404 is used to assess eligibility for (177)Lu-PSMA-617 therapy, a lower adjusted lesion-to-liver ratio should be used.