Assessing Response to PSMA Radiopharmaceutical Therapies with Single SPECT Imaging at 24 Hours After Injection

Understanding the relationship between lesion-absorbed dose and tumor response in ¹⁷⁷Lu-PSMA-617 radiopharmaceutical therapies (RPTs) remains complex. We aimed to investigate whether baseline lesion-absorbed dose can predict lesion-based responses and to explore the connection between lesion-absorbed dose and prostate-specific antigen (PSA) response. Methods: In this retrospective study, we evaluated 50 patients with 335 index lesions undergoing ¹⁷⁷Lu-PSMA-617 RPT, who had dosimetry analysis performed on SPECT/CT at 24 h after cycles 1 and 2. First, we identified the index lesions for each patient and measured the lesion-based absorbed doses. Lesion-based response was calculated after cycle 2. Additionally, PSA50 response (a decline of 50% from baseline PSA) after cycle 2 was also calculated. The respective responses for mean and maximum absorbed doses and prostate-specific membrane antigen (PSMA) volumetric intensity product (VIP-PSMA) at cycles 1 and 2 were termed SPECT_mean, SPECT_maximum, and SPECT_VIP-PSMA, respectively. Results: Of the 50 patients reviewed, 46% achieved a PSA50 response after cycle 2. Of the 335 index lesions, 58% were osseous, 32% were lymph nodes, and 10% were soft-tissue metastatic lesions. The SPECT lesion-based responses were higher in PSA responders than in nonresponders (SPECT_mean response of 46.8% ± 26.1% vs. 26.2% ± 24.5%, P = 0.007; SPECT_maximum response of 45% ± 25.1% vs. 19% ± 27.0%, P = 0.001; SPECT_VIP-PSMA response of 49.2% ± 30.3% vs. 14% ± 34.7%, P = 0.0005). An association was observed between PSA response and SPECT_VIP-PSMA response (R ² = 0.40 and P < 0.0001). A limited relationship was found between baseline absorbed dose measured with a 24-h single time point and SPECT lesion-based response (R ² = 0.05, P = 0.001, and R ² = 0.03, P = 0.007, for mean and maximum absorbed doses, respectively). Conclusion: In this retrospective study, quantitative lesion-based response correlated with patient-level PSA response. We observed a limited relationship between baseline absorbed dose and lesion-based responses. Most of the variance in response remains unexplained solely by baseline absorbed dose. Establishment of a dose-response relationship in RPT with a single time point at 24 h presented some limitations.