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

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.

• Authors: Su Bin Kim, In Ho Song, Seon Yoo Kim, Hae Young Ko, Hee Seup Kil, Dae Yoon Chi, Frederik L Giesel, Klaus Kopka, Alexander Hoepping, Joong-Hyun Chun, Hyun Soo Park, Mijin Yun, Sang Eun Kim
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 20 Issue 2 Pg. 1050-1060 (02 06 2023) ISSN: 1543-8392 [Electronic] United States
• PMID: 36583623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Radiopharmaceuticals
• PSMA-1007
• Oligopeptides
• Glutamate Carboxypeptidase II
• Antigens, Surface

Topics

• Male
• Humans
• Animals
• Mice
• Radiopharmaceuticals (pharmacokinetics)
• Heterografts
• Prostatic Neoplasms (diagnostic imaging, radiotherapy, drug therapy)
• Oligopeptides
• Glutamate Carboxypeptidase II (metabolism)
• Antigens, Surface (metabolism)
• Cell Line, Tumor