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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.    Findings  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.

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