Results from extended lymphadenectomies with [111In]PSMA-617 for intraoperative detection of PSMA-PET/CT-positive nodal metastatic prostate cancer

Abstract

Purpose: Identification of suspicious PSMA-PET/CT-positive lymph node (LN) metastases (LNM) from prostate cancer (PCa) during lymphadenectomy (LA) is challenging. We evaluated an 111 In-labelled PSMA ligand (DKFZ-617, referred to as [ 111 In]PSMA-617) as a γ-emitting tracer for intraoperative γ-probe application for resected tissue samples in PCa patients. Forty-eight hours prior to LA, [ 111 In]PSMA-617 was administered intravenously in 23 patients with suspected LNM on PSMA-PET/CT (n = 21 with biochemical relapse, n = 2 at primary therapy). Resected tissue samples (LN, LNM and fibrofatty tissue) were measured ex situ by a γ-probe expressed as counts per second (CPS norm ). [ 111 In]PSMA-617 tissue sample uptake was measured by a germanium detector for verification and calculated as %IA lbm (percent injected activity per kilogram lean body mass at time of surgery). Based on a clinical requirement for a specificity > 95%, thresholds for both ex situ measurements were chosen accordingly. Correlation of the results from PET/CT, γ-probe and germanium detector with histopathology was done. Results: Eight hundred sixty-four LNs (197 LNM) were removed from 275 subregions in 23 patients, on average 8.6 ± 14.9 LNM per patient. One hundred four of 275 tissue samples showed cancer. Median γ-probe and germanium detector results were significantly different between tumour-affected (33.5 CPS norm , 0.71 %IA lbm ) and tumour-free subregions (3.0 CPS norm , 0.03 %IA lbm ) (each p value < 0.0001). For the chosen γ-probe cut-off (CPS norm > 23) and germanium detector cut-off (%IA lbm > 0.27), 64 and 74 true-positive and 158 true-negative samples for both measurements were identified. Thirty-nine and 30 false-negative and 6 and 5 false-positive tissue samples were identified by γ-probe and germanium detector measurements.Conclusion: [ 111 In]PSMA-617 application for LA is feasible in terms of an intraoperative real-time measurement with a γ-probe for detection of tumour-affected tissue samples. γ-probe results can be confirmed by precise germanium detector measurements and were significantly different between tumour-affected and tumour-free samples.

Robot-assisted prostate-specific membrane antigen-radioguided surgery in primary diagnosed prostate cancer

“…To our knowledge this is the first prospective series on robot-assisted PSMA-targeted surgery and ePLND in the primary treatment setting. Prior PSMA-targeted surgery studies were performed in the salvage pelvic lymph node and local recurrence dissection setting (13,19,20). The technical setup used in our study is a combination of (13,17).…”

Preclinical and Clinical Status of PSMA-Targeted Alpha Therapy for Metastatic Castration-Resistant Prostate Cancer

“…Unfortunately, the chelator HBED-CC (N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'-diacetic acid) used in PSMA-11 is not suitable for the stable complexation with therapeutic radionuclides [138]. To date, PSMA-617 and PSMA I&T are the most commonly used theragnostic PSMA radioligands because they can be radiolabeled with diagnostic, e.g., 68 Ga and 44 Sc for PET and 111 In for SPECT, as well as therapeutic radiometals [138][139][140][141][142][143][144]. In an attempt to prolong circulation in the blood and therewith, to increase the dose delivered to tumors and the tumor-to-kidney ratio, PSMA ligands have been structurally modified by adding albumin-binding moieties [123,132,[145][146][147][148][149][150].…”

Radiolabeled PSMA Inhibitors

“…PSMA I&T and PSMA-617 radiolabeled with 111 In were initially used for SPECT imaging and RGS [ 75 , 79 , 80 , 109 , 110 ], with both showing detection rates lower than [ 68 Ga]Ga-PSMA-11 [ 111 ]. However, due to the limited availability of [ 111 In]InCl 3 , PSMA I&T derived Mas 3 -y-nal-k(Sub-KuE) (PSMA I&S) was developed and radiolabeled with 99m Tc [ 81 ].…”