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

Abstract

Introduction: A new therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in ¹⁷⁷Lu-PSMA-617 radioligand therapy.

Methods: On the basis of PSMA-targeted ⁶⁸Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for ¹⁷⁷Lu-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 ⁶⁸Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival.

Results: ¹⁷⁷Lu-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 SUV_max 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 SUV_max 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 ¹⁷⁷Lu-PSMA-617-treated mCRPC patients whereas ⁶⁸Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.

Keywords: 177Lu-PSMA-617; 68Ga-PSMA-11; Dosimetry; Metastasized castration; Post-therapy whole-body scintigraphy; Theragnostic concept; resistant prostate cancer.

Fig. 1

Response evaluation of PET/CT and post-therapy whole-body scintigraphy. ⁶⁸Ga-PSMA-11 PET/CT of patient no. 17 before ¹⁷⁷Lu-PSMA-617-therapy (a) and after four (b) cycles (24.9 GBq), and serial ¹⁷⁷Lu-PSMA-617 24-h whole-body scans (c). In this patient, a representative SUV_max value of lymph nodes at baseline was 65.2 which decreased to 16.1 after 4 cycles and corresponded to decreasing TU/BG ratio of 25.2 at the first therapy cycle and 3.1 at the 4th therapy cycle. PSA dropped from 76.9 to 1.27

Fig. 2

“¹⁷⁷Lu Score”: response of TU/BG ratios calculated from the 24-h whole-body scans (waterfall plots)

Fig. 3

Correlation of SUV_max values with absorbed tumor dose

Fig. 4

“PSA Score”: response of PSA following ¹⁷⁷Lu-PSMA-617 treatment (waterfall plots)

Fig. 5

Kaplan–Meier curves for PFS and OS from the start of treatment

Fig. 6

Correlation of PFS and OS with absorbed dose, SUV_max, and PSA values