Eligibility for 177Lu-PSMA therapy depends on the choice of companion diagnostic tracer: a comparison of 68Ga-PSMA-11 and 99mTc-MIP-1404 in metastatic castrate resistant prostate cancer

Abstract

Lutetium-177-prostate-specific membrane-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 > 1 on 68Ga-PSMA-11 positron emission tomography (PET) scans. We aimed to determine if an equivalent ratio is suitable for a single-photon emission computed tomography (SPECT) tracer, 99mTc-MIP-1404, and to compare lesion and lesion to normal organ ratios between the two radiotracers. Methods: Two cohorts of patients with mCRPC matched for age, prostate-specific antigen (PSA) 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 maximum standardized uptake values (SUVmax) were measured. Results: 99mTc-MIP-1404 SPECT lesion SUVmax was not significantly different from 68Ga-PSMA-11 PET (median 18.2 vs 17.3; p=0.93). However, 99mTc-MIP-1404 liver SUVmax 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 or splenic SUVmax or lesion to parotid ratios between the two tracers although there was a small difference in lesion to spleen ratios (p=0.034). Conclusions: 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.