BioChem - DOS

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

Molecular pharmaceutics

Kim, Su Bin; Song, In Ho; Kim, Seon Yoo; Ko, Hae Young; Kil, Hee Seup; Chi, Dae Yoon; Giesel, Frederik L.; Kopka, Klaus; Hoepping, Alexander; Chun, Joong-Hyun; Park, Hyun Soo; Yun, Mijin; Kim, Sang Eun

<P>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, [<SUP>18</SUP>F]PSMA-1007 has several advantages, including a comparatively long half-life, delayed renal excretion, and compatible structure with &alpha;-/&beta;-particle emitter-labeled therapeutics. This study aimed to characterize the preclinical pharmacokinetics and internal radiation dosimetry of [<SUP>18</SUP>F]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 [<SUP>18</SUP>F]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 (<I>K</I><SUB><I>i</I></SUB>) of [<SUP>18</SUP>F]PSMA-1007 to the tumor was minimal between scans performed in the same animals (within-subject coefficient of variation = 7.57%). [<SUP>18</SUP>F]PSMA-1007 uptake in the tumor was specifically decreased by 32% in <I>K</I><SUB><I>i</I></SUB> after treatment with a PSMA inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA). In the present study, we investigated the <I>in vivo</I> preclinical characteristics of [<SUP>18</SUP>F]PSMA-1007. Our data from [<SUP>18</SUP>F]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 [<SUP>177</SUP>Lu]Lu-PSMA-617), especially strategies with a quantitative radiation dose estimate for target lesions while minimizing radiation-induced toxicity to off-target tissues.</P><BR>[FIG OMISSION]</BR>

2023

American Chemical Society

1543-8384

1543-8392

20

2

pp.1050-1060

10.1021/acs.molpharmaceut.2c00788

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART122899863

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