Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone

ObjectiveThe purpose of this study is to demonstrate the consistency and reproducibility of quantitative SPECT/CT by evaluating the maximum SUV (SUVmax) in normal bone, to provide the reference value of metastatic lesions, and to evaluate the clinical implication of SUVmax changes of osseous metastasis during treatment. Material and methodsThis prospective imaging sub-study was performed as part of a phase 2 clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to the combination of pembrolizumab plus radium-223 or to radium-223 alone (NCT03093428). The maximum standardized uptake value (SUVmax) and mean Hounsfield Unit (HUmean) of normal bone as well as metastases were measured using a 1.5 cm region of interest (ROI) on CT and xSPECT Quant reconstruction on the baseline study (S0) and restaging scans. The most tracer-avid metastatic lesion in each patient on S0 was selected as a target lesion, and changes of SUVmax and HUmean of the target lesion were compared on the first restaging scan (S1). Correlations between the percentage changes of SUVmax of the target lesion with alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were assessed. ResultsTwenty-one patients were enrolled on the imaging sub-study of which 15 had paired baseline S0 and S1 data. On S0, the median SUVmax and HUmean of normal bone was 5.85 g/mL (0.42-14.98) and 133.03 (range, 28.47-461.91), respectively. The median SUVmax and HUmean of metastasis were 42.2 g/mL (range, 17.96-143.36) and 549.58 (177.87-1107.64), respectively. There was significant reduction in SUVmax (- 40.1%, range - 86.2 to + 23.5%), p < 0.001) and increase in HUmean (+ 8.3%, range - 11.3 to + 61.7%, p = 0.0479, Wilcoxon signed-rank test) of target lesions between S0 and S1. Spearman correlation between the percentage changes of SUVmax of a target lesion and both serum PSA (r = 0.33, p = 0.226) and ALP (r = 0.45, p = 0.094) were not statistically significant. ConclusionQuantitative SPECT/CT provides consistent and objective imaging parameters, which can help monitor tumor burden. The median SUVmax of metastasis at baseline was roughly 7.2-fold higher than normal bone. Quantitative SPECT/CT may help visualize the early osteoblastic treatment response in prostate cancer patients treated with radium-223 alone or combined with pembrolizumab.