99m Tc-labelled PSMA ligand for radio-guided surgery in nodal metastatic prostate cancer: proof of principle

Purpose Intraoperative identification of prostate cancer (PCa) lymph node (LN) metastases (LNM) detected by preoperative PSMA PET/CT may be facilitated by PSMA radio-guided surgery (RGS) with use of a γ-probe. Earlier we demonstrated excellent performance of the 111 In-labelled PSMA ligand DKFZ-617 ([ 111 In]In-PSMA-617) in RGS for ex situ distinction of LN vs LNM at lymphadenectomy (LA) at a single LN level. In comparison with indium-111, technetium-99m has better physical properties for γ-probe measurements, better availability and lower radiation exposure for patients and medical personnel. Against this background, we evaluated the uptake of 99m Tc-PSMA-I&S ligand at the level of single LN and its power to discriminate between unaffected LN and LNM. Methods Six patients with PCa with the suspicion of LNM on preoperative PSMA-PET/CT underwent [ 99m Tc]Tc-PSMA-I&S RGS (4 salvage LA, 2 primary LA) with intravenous injection of [ 99m Tc]Tc-PSMA-I&S 24 h prior to surgery. Resected samples were isolated manually aiming at the level of single LN. Uptake measurements were done ex situ with a high-purity germanium detector. Receiver operating characteristic (ROC) analysis was performed based on [ 99m Tc]Tc-PSMA-I&S uptake expressed as lean body mass standard uptake value (SUL). Results Separation of the tissue samples from 73 subregions resulted in 498 single samples. After final histopathology 356 LN, 160 LNM und 11 non-nodal PCa samples were identified. Median SUL of tumor-free samples (0.26) and samples with cancer (3.5) was significantly different ( p < 0.0001). ROC analysis revealed an area under the curve (AUC) of 0.917 (95% CI 0.89–0.95). Using a SUL cutoff of 1.1, sensitivity, specificity, positive predictive value, and negative predictive values were 76.6%, 94.4%, 89.4% and 86.9%. Conclusion Ex situ analysis of [ 99m Tc]Tc-PSMA-I&S uptake at single LN level showed good diagnostic performance for the ex situ distinction of tumor-bearing vs tumor-free LN during RGS.