(111)In]PSMA-I&T: expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery.

Margret Schottelius,Martina Wirtz,Tobias Maurer,Hans-Jürgen Wester,Matthias Eiber

doi:10.1186/s13550-015-0147-6

Abstract

BackgroundThe relevance of prostate-specific membrane antigen (PSMA) targeting in the clinical management of prostate cancer (PCa) is continually increasing, entailing the development of PSMA-targeted molecular probes. Recently, a first PSMA-targeted theranostic concept has been successfully implemented by [68Ga/177Lu]PSMA-I&T. To further exploit the excellent PSMA-targeting characteristics and in vivo performance of the PSMA-I&T platform, [111In]PSMA-I&T was evaluated as a complementary probe for radioguided surgery and SPECT imaging.FindingsCompared to [68Ga/177Lu]PSMA-I&T, [111In]PSMA-I&T showed unchangedly high PSMA-affinity and enhanced internalization into PSMA-expressing LNCaP PCa cells. Biodistribution studies in LNCaP xenograft-bearing mice (1 h p.i.) revealed slightly reduced background accumulation of [111In]PSMA-I&T compared to [177Lu]PSMA-I&T and identical tumor uptake of both compounds, leading to increased tumor/background ratios for [111In]PSMA-I&T. An exemplary patient with metastatic PCa underwent preoperative [68Ga]HBED-CC-PSMA PET/CT (1 h p.i.) and [111In]PSMA-I&T SPECT/CT (4 h p.i.), followed by prostatectomy and radioguided extended pelvic lymphadenectomy (24 h p.i.). In [111In]PSMA-I&T SPECT/CT, the previously identified PCa lesions ([68Ga]HBED-CC-PSMA PET/CT) showed high tracer accumulation and were also detectable using planar scintigraphy. The intraoperative use of a hand-held gamma probe allowed detection and resection of all [111In]PSMA-I&T-accumulating lesions. The presence of PSMA-positive tumor tissue in the resected specimens was confirmed histopathologically and via [111In]PSMA-I&T autoradiography.Conclusions[111In]PSMA-I&T shows efficient PSMA targeting in vitro and in vivo, combined with low background accumulation. In an exemplary PCa patient, [111In]PSMA-I&T was successfully applied for preoperative SPECT/CT visualization and radioguided resection of PSMA-positive lesions, hinting towards a high value of [111In]PSMA-I&T as a complementary tool to [68Ga/177Lu]PSMA-I&T in the clinical management of prostate cancer.

Highlights

The relevance of prostate-specific membrane antigen (PSMA) targeting in the clinical management of prostate cancer (PCa) is continually increasing, entailing the development of PSMA-targeted molecular probes
Modern clinical management of prostate cancer increasingly relies on exploiting the prostate-specific membrane antigen (PSMA) as a molecular target both for imaging and for treatment of prostate cancer (PCa)
PSMA is abundantly expressed on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues

Summary

Introduction

The relevance of prostate-specific membrane antigen (PSMA) targeting in the clinical management of prostate cancer (PCa) is continually increasing, entailing the development of PSMA-targeted molecular probes. In an exemplary PCa patient, [111In]PSMA-I&T was successfully applied for preoperative SPECT/CT visualization and radioguided resection of PSMA-positive lesions, hinting towards a high value of [111In]PSMA-I&T as a complementary tool to [68Ga/177Lu]PSMA-I&T in the clinical management of prostate cancer.

Results

Conclusion