Kazuta Nobuki, Nakashima Kazuma, Tarumizu Yuta, Sato Takumi, Maya Yoshifumi, Watanabe Hiroyuki, Ono Masahiro
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Research Center, Nihon Medi-Physics Co., Ltd., 3-1 Kitasode, Sodegaura-shi, Chiba 299-0266, Japan.
Mol Pharm. 2025 Jan 6;22(1):377-386. doi: 10.1021/acs.molpharmaceut.4c00974. Epub 2024 Nov 30.
Radiotheranostics using prostate-specific membrane antigen (PSMA)-targeting radioligands offers precision medicine by performing radionuclide therapy based on results of diagnosis. Albumin binder (ALB) binds to albumin reversibly and contributes to effective radiotheranostics by enhancing tumor accumulation of PSMA-targeting radioligands. We newly developed two ALB-containing PSMA-targeting radioligands including dual functional linkers, a hydrophilic linker, d-glutamic acid, and a hydrophobic linker, 4-(aminomethyl)benzoic acid, with the opposite arrangement (PNT-DA6 and PNT-DA7). A biodistribution study of [In]In-PNT-DA6 indicated that the introduction and arrangement of dual functional linkers contributed to improved pharmacokinetics. A single photon emission computed tomography study of [In]In-PNT-DA6 produced a clear PSMA-expressing tumor image. Moreover, [Ac]Ac-PNT-DA6 showed the inhibition of tumor growth in targeted radionuclide therapy in PSMA-expressing tumor-bearing mice. These results indicated that [In]In-PNT-DA6 and [Ac]Ac-PNT-DA6 exhibited useful characteristics as PSMA-targeting radiotheranostic ligands.
使用靶向前列腺特异性膜抗原（PSMA）的放射性配体进行放射治疗诊断，可根据诊断结果进行放射性核素治疗，从而提供精准医疗。白蛋白结合剂（ALB）与白蛋白可逆结合，并通过增强靶向PSMA的放射性配体在肿瘤中的蓄积，促进有效的放射治疗诊断。我们新开发了两种含ALB的靶向PSMA的放射性配体，包括具有相反排列的双功能连接体、亲水性连接体d-谷氨酸和疏水性连接体4-（氨基甲基）苯甲酸（PNT-DA6和PNT-DA7）。[铟]铟-PNT-DA6的生物分布研究表明，双功能连接体的引入和排列有助于改善药代动力学。[铟]铟-PNT-DA6的单光子发射计算机断层扫描研究产生了清晰的表达PSMA的肿瘤图像。此外，[锕]锕-PNT-DA6在表达PSMA的荷瘤小鼠的靶向放射性核素治疗中显示出对肿瘤生长的抑制作用。这些结果表明，[铟]铟-PNT-DA6和[锕]锕-PNT-DA6作为靶向PSMA的放射治疗诊断配体具有有用的特性。
