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. 2015 Dec;5(1):68.
doi: 10.1186/s13550-015-0147-6. Epub 2015 Nov 25.

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

Margret Schottelius  1 , Martina Wirtz  2 , Matthias Eiber  3 , Tobias Maurer  4 , Hans-Jürgen Wester  5
Affiliations

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

Margret Schottelius et al. EJNMMI Res. 2015 Dec.

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.

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.

Keywords: 111In; 177Lu; Imaging; PET; PSMA; PSMA-I&T; Prostate-specific membrane antigen; Radioguided surgery; SPECT; Targeted radionuclide therapy.

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Figures

Fig. 1
Fig. 1
Schematic representation of the PSMA-I&T-based theranostic concept for the clinical management of PCa
Fig. 2
Fig. 2
Comparative biodistribution of [111In]- and [177Lu]PSMA-I&T in LNCaP tumor-bearing mice 1 h p.i. Biodistribution studies were carried out using LNCaP xenograft-bearing CB17 SCID ([111In]PSMA-I&T) or CD-1 nu/nu ([177Lu]PSMA-I&T) mice. Animals were injected intravenously with 1.4 MBq (0.2 nmol) of the respective PSMA-I&T analog. Data are represented as % injected dose per gram tissue (%iD/g) and are means ± SD (groups of n = 5). Animal experiments were conducted in accordance with the German Animal Welfare Act (Deutsches Tierschutzgesetz, approval no. 55.2-1-54-2532-71-13)
Fig. 3
Fig. 3
Preoperative imaging using [68Ga]HBED-CC PSMA PET/CT and [111In]PSMA-I&T SPECT/CT and planar scintigraphy. The human study was approved by the institutional review boards of the participating medical institutions, and the patient provided signed informed consent. a [68Ga]HBED-CC PSMA PET/CT (MIP) 1 h p.i. b planar scintigraphy (ventral and dorsal view) 4 h p.i. of 155 MBq [111In]PSMA-I&T. d, g Axial [68Ga]HBED-CC PSMA PET/CT images of the primary tumor in the prostate (d) and a representative lymph node (g). c, f  Corresponding CT images, and e, h Corresponding axial [111In]PSMA-I&T SPECT/CT images of the primary tumor in the prostate (e) and a representative lymph node (h). i, j H&E staining and 111In-autoradiography of cryosections from resected prostate tissue
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