^99mTc-MIP-1404 SPECT/CT Companion Diagnostic for¹⁷⁷Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer

Our objective was to determine the feasibility, diagnostic performance, and predictive value of ^99mTc-MIP-1404 SPECT in patients undergoing baseline staging and assessment of eligibility for prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy (RPT) for metastatic castration-resistant prostate cancer. <b>Methods:</b> Data of 46 patients undergoing ^99mTc-MIP-1404 planar scintigraphy and SPECT/CT for staging and assessment of eligibility for ¹⁷⁷Lu-PSMA RPT were retrospectively analyzed. Overall image quality was assessed, and images were visually analyzed for the presence and localization of pathologic uptake. Metastatic uptake was visually scored using a 3-point scale. ^99mTc-MIP-1404 findings were compared with the results of posttherapeutic ¹⁷⁷Lu-PSMA scans in patients subsequently commencing RPT (<i>n</i> = 35). The predictive and prognostic significance of uptake intensity in ^99mTc-MIP-1404 scans was evaluated. <b>Results:</b> The image quality of ^99mTc-MIP-1404 scans was rated as excellent in 98% of cases. Imaging results were concordant in 206 of 210 localizations, demonstrating almost perfect agreement with ¹⁷⁷Lu-PSMA scans (κ = 0.957 [95% CI, 0.916-0.999]). Uptake intensity higher than liver uptake identified responders (<i>P</i> = 0.0115) and was associated with prolonged progression-free survival (median, 146 vs. 96 d; hazard ratio for progression, 0.3838 [95% CI, 0.1721-0.8556]; <i>P</i> = 0.0192). In multivariable analysis, ^99mTc-MIP-1404 uptake higher than in liver emerged as an independent predictor of treatment response (odds ratio, 12.37 [95% CI, 1.613-203.3]; <i>P</i> = 0.0319). Nevertheless, 27% of responders demonstrated uptake no higher than that in the liver. <b>Conclusion:</b> ^99mTc-MIP-1404 imaging is suitable for assessment of eligibility for RPT in patients with advanced metastatic castration-resistant prostate cancer. In particular, pretherapeutic uptake intensity is predictive of response to ¹⁷⁷Lu-PSMA RPT.