Eligibility for177Lu-PSMA Therapy Depends on the Choice of Companion Diagnostic Tracer: A Comparison of68Ga-PSMA-11 and99mTc-MIP-1404 in Metastatic Castration-Resistant Prostate Cancer

¹⁷⁷Lu-prostate-specific membrane antigen-617 (¹⁷⁷Lu-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 ⁶⁸Ga-PSMA-11 PET scans. We aimed to determine whether an equivalent ratio is suitable for a SPECT tracer, ^99mTc-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 ^99mTc-MIP-1404 SPECT/CT (n = 25) or ⁶⁸Ga-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:^99mTc-MIP-1404 SPECT lesion SUV_max was not significantly different from ⁶⁸Ga-PSMA-11 PET (median, 18.2 vs. 17.3; P = 0.93). However, ^99mTc-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 ⁶⁸Ga-PSMA-11 and ^99mTc-MIP-1404. Therefore, if ^99mTc-MIP-1404 is used to assess eligibility for ¹⁷⁷Lu-PSMA-617 therapy, a lower adjusted lesion-to-liver ratio should be used.