title: [(111)In]PSMA-I&T: expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery.
abstract: BACKGROUND
  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. Recently, a first PSMA-targeted theranostic concept has been successfully implemented by [(68)Ga/(177)Lu]PSMA-I&T. To further exploit the excellent PSMA-targeting characteristics and in vivo performance of the PSMA-I&T platform, [(111)In]PSMA-I&T was evaluated as a complementary probe for radioguided surgery and SPECT imaging.
  
  
  RESULTS
  Compared to [(68)Ga/(177)Lu]PSMA-I&T, [(111)In]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 [(111)In]PSMA-I&T compared to [(177)Lu]PSMA-I&T and identical tumor uptake of both compounds, leading to increased tumor/background ratios for [(111)In]PSMA-I&T. An exemplary patient with metastatic PCa underwent preoperative [(68)Ga]HBED-CC-PSMA PET/CT (1 h p.i.) and [(111)In]PSMA-I&T SPECT/CT (4 h p.i.), followed by prostatectomy and radioguided extended pelvic lymphadenectomy (24 h p.i.). In [(111)In]PSMA-I&T SPECT/CT, the previously identified PCa lesions ([(68)Ga]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 [(111)In]PSMA-I&T-accumulating lesions. The presence of PSMA-positive tumor tissue in the resected specimens was confirmed histopathologically and via [(111)In]PSMA-I&T autoradiography.
  
  
  CONCLUSIONS
  [(111)In]PSMA-I&T shows efficient PSMA targeting in vitro and in vivo, combined with low background accumulation. In an exemplary PCa patient, [(111)In]PSMA-I&T was successfully applied for preoperative SPECT/CT visualization and radioguided resection of PSMA-positive lesions, hinting towards a high value of [(111)In]PSMA-I&T as a complementary tool to [(68)Ga/(177)Lu]PSMA-I&T in the clinical management of prostate cancer.
authors.affiliation: Chair for Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meissner-Strasse 3, 85748, Garching, Germany. m.schottelius@lrz.tum.de.
authors.forename: Margret
authors.initials: M
authors.lastname: Schottelius
authors.affiliation: Chair for Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meissner-Strasse 3, 85748, Garching, Germany. martina.wirtz@gmx.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Wirtz
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, Munich, Germany. matthias.eiber@tum.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eiber
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, Munich, Germany. tobias.maurer@tum.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Chair for Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meissner-Strasse 3, 85748, Garching, Germany. h.j.wester@tum.de.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
keywords: 111In; 177Lu; Imaging; PET; PSMA; PSMA-I&T; Prostate-specific membrane antigen; Radioguided surgery; SPECT; Targeted radionuclide therapy