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 (K i ) 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 K i 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.

Radiomics and Artificial Intelligence in Radiotheranostics: A Review of Applications for Radioligands Targeting Somatostatin Receptors and Prostate-Specific Membrane Antigens

“…In the case of [ 18 F]PSMA-1007, structurally related to PSMA-617 ( 18 F is labeled to DKFZ-PSMA-617 initially developed for 68 Ga-ligand), the liver metabolizes the PSMA-1007 ligand pharmaceutical instead of urinary excretion [87]. Moreover, in a metaphor for the chemical structure, the uptake of tumors and normal organs are very similar to [ 18 F]PSMA-1007 and [ 177 Lu]Lu-PSMA-617 compounds [90,91]. Therefore, [ 18 F]PSMA-1007 can be viewed as a well-suited diagnostic equivalent to PSMA-617, which may help guide the choice of patients referred to PSMA-617 therapy.…”

Radiomics and Artificial Intelligence in Radiotheranostics: A Review of Applications for Radioligands Targeting SSTR and PSMA

“…In the case of [ 18 F]PSMA-1007, structurally related to PSMA-617 ( 18 F is labeled to DKFZ-PSMA-617 initially developed for 68 Ga-ligand), the liver metabolizes the PSMA-1007 ligand pharmaceutical instead of urinary excretion [87]. Moreover, in a metaphor for the chemical structure, the uptake of tumors and normal organs are very similar to [ 18 F]PSMA-1007 and [ 177 Lu]Lu-PSMA-617 compounds [90,91]. Therefore, [ 18 F]PSMA-1007 can be viewed as a well-suited diagnostic equivalent to PSMA-617, which may help guide the choice of patients referred to PSMA-617 therapy.…”