The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up

Introduction A new therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in Lu-177-PSMA-617 radioligand therapy. Methods On the basis of PSMA-targeted Ga-68-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for Lu-177-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6-10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and Ga-68-PSMA-11 PET/CT data were compared and related to progression free and overall survival. Results Lu-177-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 +/- 2.64; range 1.10-13.00 Gy/GBq), lymph node (3.12 +/- 2.07; range 0.70-8.70 Gy/GBq), and liver (2.97 +/- 1.38; range 0.76-5.00 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 24 GBq. Any PSA decrease after the first cycle was found in 23/32 (72%), after the second cycle in 22/32 (69%), after the third cycle in 16/28 (57%), and after the fourth cycle in 8/18 (44%) patients. Post-therapy 24 h WB scintigraphy showed decreased tumor-to-background ratios in 24/32 (75%) after the first therapy cycle, after the second cycle in 17/29 (59%), and after the third cycle in 13/21 (62%) patients. The median PFS was 7 months and the median OS 12 months. In the group of PSA responders (n = 22) the median OS was 17 months versus 11 months in the group of non-responders (n = 10), p < 0.05. Decreasing SUVmax values were found for parotid (15.93 +/- 6.23 versus 12.33 +/- 4.07) and submandibular glands (17.65 +/- 7.34 versus 13.12 +/- 4.62) following treatment, along with transient (n = 6) or permanent (n = 2) xerostomia in 8/32 (25%) patients. In 3/32 patients, nephrotoxicity changed from Grade 2 to 3, whereas neither Grade 4 nephrotoxicity nor hematotoxicity was found. In most patients a good agreement was observed for the visual interpretation of the tracer accumulation between 24 h WB and PET/CT scans. However, no significance could be calculated for baseline-absorbed tumor doses and SUVmax values of tumor lesions. 5/32 (16%) patients showed a mixed response pattern, which resulted in disease progression over time. Conclusion Serial PSA measurements and post-therapy 24 h WB scintigraphy seems to allow a sufficiently accurate follow-up of Lu-177-PSMA-617-treated mCRPC patients whereas Ga-68-PSMA-11 PET/CT should be performed for patient selection and final response assessment.