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 177 Lu-PSMA-617 radioligand therapy. Methods On the basis of PSMA-targeted 68 Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for 177 Lu-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 68 Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival. Results 177 Lu-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 177 Lu-PSMA-617-treated mCRPC patients whereas 68 Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

“…It is less clear whether low PSMA expression levels result in reduced responsiveness to therapy by way of lower levels of targetable substrate. Many studies have excluded patients with poor PSMA expression on imaging, even studies that have attempted to correlate standardized uptake value (SUV) scores with PSA decline [14][15][16]. Consequently, studies that have shown no relationship between SUV scores and PSA decline have primarily included patients with high PSMA expression based on PET imaging.…”

“…The median overall survival was 13.5 months. In a study involving 32 patients, also selected based on favorable PSMA expression on imaging, 71.9% (23/32) experienced PSA decline, and median overall survival was 12 months (17 months in responders vs. 11 months in non-responders) [ 15 ]. Patients underwent two to six cycles, with six-week intervals.…”

“…Since then, numerous retrospective studies with larger groups of patients have been published by the same group. In 2017, Ahmadzadehfar et al 9% (23/32) experienced PSA decline, and median overall survival was 12 months (17 months in responders vs. 11 months in non-responders)[15]. Patients underwent two to six cycles, with six-week intervals.…”

Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

“…Biochemical response assessment was based on PSA-levels according to previously described protocols [ 19 , 20 , 21 ]. The complete biochemical response was defined as a non-measurable PSA level (0 ng/mL) after PSMA RLT, partial biochemical response (PR) defined a PSA-decline ≥50%, stable disease (SD) as a PSA change between −50% and +25%, and progressive disease (PD) as a PSA increase ≥25%.…”

Metastatic Heterogeneity of Breast Cancer: Companion and Theranostic Approach in Nuclear Medicine

“…A typical example in theranostics is the use of β + emitter 68-Gallium 68 ( 68 Ga) tracers for diagnosis, followed by targeted therapy by labeling a similar or the same compound with β − radionuclides, such as 177-Lutetium ( 177 Lu) or 90-Yttrium ( 90 Y). These three radioelements with similar chemical conformations can be complexed to the same group for the radio-labeling of the molecule of interest [66][67][68]. The great advances in the field of theranostics has led to remarkable progress in the management of patients with prostate cancer with the use of 68 Ga-PSMA-617/ 177 Lu-PSMA-617, or with neuroendocrine tumors with the use of 68 Ga/ 177 Lu-DOTA-TATE, while showing limited side effects [69][70][71].…”