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

Cordula A Jilg; Kathrin Reichel; Christian Stoykow; H Christian Rischke; Mark Bartholomä; Vanessa Drendel; Moritz von Büren; Wolfgang Schultze-Seemann; Philipp T Meyer; Michael Mix

doi:10.1186/s13550-020-0598-2

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

EJNMMI Res. 2020 Mar 6;10(1):17. doi: 10.1186/s13550-020-0598-2.

Authors

Affiliations

¹ Department of Urology, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstraße 55, 79106, Freiburg, Germany. cordula.jilg@uniklinik-freiburg.de.
² Department of Urology, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstraße 55, 79106, Freiburg, Germany.
³ Department of Nuclear Medicine, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Radiation Oncology, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁵ Institute for Pathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁶ German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany.
⁷ Department of Medical Imaging and Clinical Oncology, Nuclear Medicine Division, Faculty of Medicine and Health Science, Stellenbosch University, Stellenbosch, South Africa.

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 ¹¹¹In-labelled PSMA ligand (DKFZ-617, referred to as [¹¹¹In]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, [¹¹¹In]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). [¹¹¹In]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: [¹¹¹In]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.

Keywords: Lymphadenectomy; Prostate cancer; Radio-guided surgery; Salvage lymph node dissection; [111In]PSMA.