177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer and Prior 223Ra (RALU Study).

223Ra-dichloride (223Ra) and 177Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of 223Ra and 177Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate 177Lu-PSMA safety and efficacy in patients with mCRPC previously treated with 223Ra. Methods: The radium→lutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 223Ra dose and, in any subsequent therapy line, at least 1 177Lu-PSMA dose. Primary endpoints included the incidence of adverse events (AEs), serious AEs, grade 3-4 hematologic AEs, and abnormal laboratory values. Secondary endpoints included overall survival, time to next treatment/death, and change from baseline in serum prostate-specific antigen and alkaline phosphatase levels. Results: Data were from 133 patients. Before 177Lu-PSMA therapy, 56% (75/133) of patients received at least 4 life-prolonging therapies; all patients received 223Ra (73% received 5-6 injections). Overall, 27% (36/133) of patients received at least 5 177Lu-PSMA infusions. Any-grade treatment-emergent AEs were reported in 79% (105/133) of patients and serious AEs in 30% (40/133). The most frequent grade 3-4 laboratory abnormalities were anemia (30%, 40/133) and thrombocytopenia (13%, 17/133). Median overall survival was 13.2 mo (95% CI, 10.5-15.6 mo) from the start of 177Lu-PSMA. Conclusion: In this real-world setting, 223Ra followed by 177Lu-PSMA therapy in heavily pretreated patients with mCRPC was clinically feasible, with no indication of impairment of 177Lu-PSMA safety or effectiveness.

[18F]-PSMA-1007-PET for evaluation of kidney function.

PURPOSE: Prostate-specific membrane antigen (PSMA) is present in the proximal tubule cells of the kidneys. This results in high renal tracer uptake in PSMA-PET, which may contain useful information on renal function. As part of the evaluation for [177Lu]-PSMA therapies, patients undergo PSMA-PET and additional [99mTc]-mercapto-acetyltriglycine (MAG3) scintigraphy to assess renal function. Aim of this study was to evaluate estimation of renal function with [18F]-PSMA-1007-PET/CT (PSMA-PET) by comparison to timely MAG3-scintigraphies. MATERIALS AND METHODS: We retrospectively investigated 73 prostate cancer patients with 93 timely available PSMA-PET/CT, MAG3-scintigraphies and serum creatinine. For determination of split renal function in PSMA-PET/CT, we evaluated the relative unilateral total renal PSMA uptake, i.e. SUVmean multiplied by the renal volume (SRFPSMA-TOTAL) and relative unilateral maximal standardized uptake value (SRFSUV). These were compared to MAG3 split renal function (SRFMAG3) using Pearson correlation and receiver operating characteristics analysis. For determination of global renal function, correlation of bilateral total renal PSMA uptake with MAG3 tubular excretion rate and serum creatinine was assessed. RESULTS: SRFMAG3 was strongly correlated with SRFPSMA-TOTAL (r= 0.872, p<0.001) and with SRFSUV (r=0.815, p<0.001). Relevant abnormalities of SRFMAG3 (unilateral renal function < 25 %) could be detected with sensitivities and specificities of 90% and 92% for SRFPSMA-TOTAL, and 80% and 95% for SRFSUV. Measures of absolute renal function were only weakly correlated with bilateral total renal PSMA uptake. CONCLUSION: Renal [18F]-PSMA-1007 uptake allowed to quantify renal split function with good accuracy based on SRFPSMA-TOTAL or SRFSUV.

Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases-A Repeatability Study.

The apparent diffusion coefficient (ADC) is a candidate marker of treatment response in osteoblastic metastases that are not evaluable by morphologic imaging. However, it is unclear whether the ADC meets the basic requirement for reliable treatment response evaluation, namely a low variance of repeated measurements in relation to the differences found between viable and nonviable metastases. The present study addresses this question by analyzing repeated in vivo ADCmedian measurements of 65 osteoblastic metastases in nine patients, as well as phantom measurements. PSMA-PET served as a surrogate for bone metastasis viability. Measures quantifying repeatability were calculated and differences in mean ADC values according to PSMA-PET status were examined. The relative repeatability coefficient %RC of ADCmedian measurements was 5.8% and 12.9% for phantom and in vivo measurements, respectively. ADCmedian values of bone metastases ranged from 595×10-6mm2/s to 2090×10-6mm2/s with an average of 63% higher values in nonviable metastases compared with viable metastases (p < 0.001). ADC shows a small repeatability coefficient in relation to the difference in ADC values between viable and nonviable metastases. Therefore, ADC measurements fulfill the technical prerequisite for reliable treatment response evaluation in osteoblastic metastases.

Safety and Survival Outcomes of 177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer with Prior 223Ra treatment: The RALU Study.

The radium lutetium (RALU) study evaluated the feasibility of sequential α- and ß-emitter use in patients with bone-predominant metastatic castration-resistant prostate cancer. Methods: This preplanned interim retrospective analysis investigated safety and survival outcomes with 177Lu-PSMA in patients treated with prior 223Ra. Results: Forty-nine patients were evaluated. Patients received a median of 6 223Ra injections; 59% of patients received at least 4 177Lu-PSMA cycles. Most (69%) patients received at least 4 life-prolonging therapies before 177Lu-PSMA. Common Terminology Criteria for Adverse Events grade 3-4 treatment-emergent adverse events during 177Lu-PSMA therapy and a 30-d follow-up period included anemia (18%) and thrombocytopenia (2%). Median overall survival was 12.6 mo (95% CI, 8.8-16.1 mo) and 31.4 mo (95% CI, 25.7-37.6 mo) from starting 177Lu-PSMA or 223Ra, respectively. Conclusion: 177Lu-PSMA treatment was well tolerated in patients who had received prior 223Ra. 223Ra use before 177Lu-PSMA is feasible and can be considered for future assessment of the optimal treatment sequence.