2. Academic Validation
  3. Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [18F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [18F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

  • Mol Pharm. 2023 Feb 6;20(2):1050-1060. doi: 10.1021/acs.molpharmaceut.2c00788.
Su Bin Kim 1 2,  In Ho Song 2,  Seon Yoo Kim 3,  Hae Young Ko 3,  Hee Seup Kil 4,  Dae Yoon Chi 4,  Frederik L Giesel 5,  Klaus Kopka 6 7 8 9,  Alexander Hoepping 10,  Joong-Hyun Chun 3,  Hyun Soo Park 2 11,  Mijin Yun 3,  Sang Eun Kim 2 11 12 13
Affiliations

Affiliations

  • 1 Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul08826, Korea.
  • 2 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam13620, Korea.
  • 3 Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul03722, Korea.
  • 4 Research Institute of Radiopharmaceuticals, FutureChem Co. Ltd, Seoul04793, Korea.
  • 5 Department of Nuclear Medicine, Heinreich-Heine-University, University Hospital Duesseldorf, Duesseldorf40225, Germany.
  • 6 Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR) e.v., Bautzner Landstrasse 400, Dresden01328, Germany.
  • 7 Technische Universität Dresden, Faculty of Chemistry and Food Chemistry, School of Science, Dresden01069, Germany.
  • 8 National Center for Tumor Diseases (NCT) Dresden, University Hospital Carl Gustav Carus, Fetscherstraße 74, Dresden01307, Germany.
  • 9 German Cancer Consortium (DKTK), Partner Site Dresden, Dresden01307, Germany.
  • 10 Department of Medicinal Chemistry, ABX Advanced Biochemical Compounds GmbH, Radeberg1454, Germany.
  • 11 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul08826, Korea.
  • 12 Advanced Institutes of Convergence Technology, 145 Gwanggyo-ro, Yeongtong-gu, Suwon16229, Korea.
  • 13 BIK Therapeutics Inc., 172 Dolma-ro, Bundang-gu, Seongnam13605, Korea.
PMID: 36583623 DOI: 10.1021/acs.molpharmaceut.2c00788
Abstract

Several radiolabeled prostate-specific membrane antigen (PSMA)-targeted agents have been developed for detecting prostate Cancer, using positron emission tomography imaging and targeted radionuclide therapy. Among them, [18F]PSMA-1007 has several advantages, including a comparatively long half-life, delayed renal excretion, and compatible structure with α-/β-particle emitter-labeled therapeutics. This study aimed to characterize the preclinical pharmacokinetics and internal radiation dosimetry of [18F]PSMA-1007, as well as its repeatability and specificity for target binding using prostate tumor-bearing mice. In PSMA-positive tumor-bearing mice, the kidney showed the greatest accumulation of [18F]PSMA-1007. The distribution in the tumor attained its peak concentration of 2.8%ID/g at 112 min after intravenous injection. The absorbed doses in the tumor and salivary glands were 0.079 ± 0.010 Gy/MBq and 0.036 ± 0.006 Gy/MBq, respectively. The variance of the net influx (Ki) of [18F]PSMA-1007 to the tumor was minimal between scans performed in the same Animals (within-subject coefficient of variation = 7.57%). [18F]PSMA-1007 uptake in the tumor was specifically decreased by 32% in Ki after treatment with a PSMA Inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA). In the present study, we investigated the in vivo preclinical characteristics of [18F]PSMA-1007. Our data from [18F]PSMA-1007 PET/computed tomography (CT) studies in a subcutaneous prostate Cancer xenograft mouse model supports clinical therapeutic strategies that use paired therapeutic radiopharmaceuticals (such as [177Lu]Lu-PSMA-617), especially strategies with a quantitative radiation dose estimate for target lesions while minimizing radiation-induced toxicity to off-target tissues.

Keywords

[18F]PSMA-1007; biodistribution; internal radiation dosimetry; positron emission tomography; theranostics.

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