⁶⁸Ga-PSMA PET/CT for Response Evaluation of²²³Ra Treatment in Metastatic Prostate Cancer

Abstract

CT and bone scintigraphy are not useful for response evaluation of bone metastases to 223 Ra treatment in metastatic castration-resistant prostate cancer (mCRPC). PET using 68 Ga prostate-specific membrane antigen 11 ( 68 Ga-PSMA) is a promising tool for response evaluation of mCRPC. The aim of this study was to determine the utility of 68 Ga-PSMA PET/CT for response evaluation of 223 Ra treatment in patients with mCRPC. Methods: Within this prospective, multicenter, imaging discovery study, 28 patients with mCRPC, eligible for 223 Ra treatment, were included between 2019 and 2022. Patients received 223 Ra according to the standard of care. Study procedures included CT, bone scintigraphy, and 68 Ga-PSMA PET/CT at baseline, after 3 and 6 cycles of 223 Ra treatment, and on treatment failure. Response to 223 Ra treatment was visually assessed on all 3 imaging modalities. Total tumor volume within bone (TTV bone ) was determined on 68 Ga-PSMA PET/CT. Intrapatient heterogeneity in response was studied using a newly developed image-registration tool for sequential images of PET/CT. Results were compared with failure-free survival (good responders vs. poor responders; cutoff, 24 wk) and alkaline phosphatase (ALP) response after 3 cycles. Results: Visual response assessment criteria could not distinguish good responders from poor responders on 68 Ga-PSMA PET/CT and bone scintigraphy. For 68 Ga-PSMA PET/CT, TTV bone at baseline was lower in good responders than in poor responders, whereas TTV bone increased in both groups during treatment. TTV bone was higher in patients with new extraosseous metastases during 223 Ra treatment. Although TTV bone and ALP correlated at baseline, changes in TTV bone and ALP on treatment did not. 68 Ga-PSMA response of TTV bone showed intrapatient heterogeneity in most patients. Conclusion: mCRPC patients with lower TTV bone on 68 Ga-PSMA PET/CT have the best clinical outcome after 223 Ra treatment. Response is highly heterogeneous in most patients. A decrease in ALP, which occurred in most patients, was not correlated with a decrease in TTV bone , which might make one question the value of ALP for disease monitoring during 223 Ra treatment in clinical practice.

Advancements in PSMA ligand radiolabeling for diagnosis and treatment of prostate cancer: a systematic review

“…This information plays a pivotal role in guiding treatment decisions for prostate cancer patients. Additionally, for individuals undergoing PSMA radionuclide therapy, alterations in PSMA uptake levels can be utilized to assess the treatment’s effectiveness, where a reduction in uptake may indicate a positive treatment response on the tumor ( 25 ). Earlier investigations have established that PSMA (Prostate-Specific Membrane Antigen) is a membrane protein that exhibits high expression in prostate tissue.…”

“…68 Ga-PSMA-11 PET/CT stands out as a valuable tool for evaluating metastatic castration-resistant prostate cancer (mCRPC), enhancing the precision of staging, and aiding in crucial clinical decision-making processes. With its high sensitivity and specificity, this imaging modality provides detailed insights into the localization and extent of metastatic lesions, empowering doctors to make well-informed decisions on treatment strategies and patient management for those facing advanced prostate cancer ( 25 , 26 ). In contrast to other imaging techniques, 68 Ga-PSMA-11 PET proves highly effective in detecting small, distant, and atypical metastases associated with prostate cancer, including instances of intraocular ( 27 ) and isolated peritoneal metastases ( 28 ).…”