Targeted α-therapy using astatine ((211)At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound.
Targeted α-therapy using astatine ((211)At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound.
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DOI：
10.1007/s00259-022-06016-z
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发表时间：
2023-02
影响因子：
9.1
通讯作者：
Fukase, Koichi
中科院分区：
文献类型：
--
作者：
Watabe, Tadashi;Kaneda-Nakashima, Kazuko;Shirakami, Yoshifumi;Kadonaga, Yuichiro;Ooe, Kazuhiro;Wang, Yang;Haba, Hiromitsu;Toyoshima, Atsushi;Cardinale, Jens;Giesel, Frederik L.;Tomiyama, Noriyuki;Fukase, Koichi
针对前列腺特异性膜抗原（PSMA）的靶向α-治疗（TAT）是治疗转移性去势抵抗性前列腺癌（CRPC）的一种有前景的治疗方法。砹是一种α-发射体（半衰期为7.2 h），可由30-MeV回旋加速器产生。本研究评估了211at标记的PSMA化合物对小鼠异种移植模型的治疗效果。采用人前列腺癌细胞（LNCaP）皮下移植NOD/SCID小鼠，建立肿瘤异种移植模型。[211At]PSMA1, [211At]PSMA5，或[211At]PSMA6分别给予LNCaP异种移植小鼠3和24 h，评估其生物分布。通过给予[211At]PSMA1(0.40±0.07 MBq), [211At]PSMA5（0.39±0.03 MBq）或生理盐水来评估其治疗效果。给药后3周和6周对危险器官进行组织病理学评估。与[211At]PSMA1和[211At]PSMA6相比，[211At]PSMA5的肿瘤潴留率更高（3小时时为30.6±17.8,12.4±4.8和19.1±4.5% ID/g，而24小时时分别为40.7±2.6,8.7±3.5和18.1±2.2%ID/g），而[211At]PSMA1的肾脏排泄优于[211At]PSMA5和[211At]PSMA6。给药后[2111at]PSMA5对肿瘤生长有良好的治疗效果。[2111at]PSMA1也表现出明显的治疗效果；但与[2111at]PSMA5相比，肿瘤大小相对较大。在组织病理学评估中，在给药[2111at]PSMA5后3周和6周在肾脏中检测到再生小管。使用[2111at]PSMA5的TAT在正常器官中具有良好的肿瘤生长抑制作用，且副作用最小。[2111at]PSMA5应该被认为是治疗转移性CRPC的一种新的可能的TAT，并且有必要进行转译前瞻性试验。在线版本包含补充材料，可在10.1007/s00259-022-06016-z获得。
Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron. This study evaluated the treatment effect of 211At-labeled PSMA compounds in mouse xenograft models. Tumor xenograft models were established by subcutaneous transplantation of human prostate cancer cells (LNCaP) in NOD/SCID mouse. [211At]PSMA1, [211At]PSMA5, or [211At]PSMA6 was administered to LNCaP xenograft mice to evaluate biodistribution at 3 and 24 h. The treatment effect was evaluated by administering [211At]PSMA1 (0.40 ± 0.07 MBq), [211At]PSMA5 (0.39 ± 0.03 MBq), or saline. Histopathological evaluation was performed for the at-risk organs at 3 and 6 weeks after administration. [211At]PSMA5 resulted in higher tumor retention compared to [211At]PSMA1 and [211At]PSMA6 (30.6 ± 17.8, 12.4 ± 4.8, and 19.1 ± 4.5 %ID/g at 3 h versus 40.7 ± 2.6, 8.7 ± 3.5, and 18.1 ± 2.2%ID/g at 24 h, respectively), whereas kidney excretion was superior in [211At]PSMA1 compared to [211At]PSMA5 and [211At]PSMA6. An excellent treatment effect on tumor growth was observed after [211At]PSMA5 administration. [211At]PSMA1 also showed a substantial treatment effect; however, the tumor size was relatively larger compared to that with [211At]PSMA5. In the histopathological evaluation, regenerated tubules were detected in the kidneys at 3 and 6 weeks after the administration of [211At]PSMA5. TAT using [211At]PSMA5 resulted in excellent tumor growth suppression with minimal side effects in the normal organs. [211At]PSMA5 should be considered a new possible TAT for metastatic CRPC, and translational prospective trials are warranted. The online version contains supplementary material available at 10.1007/s00259-022-06016-z.
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在靶向α疗法的临床试验中注射astatide钠（[[（211）at] Naat）的适当使用手册（第一版）。
影响因子：
2.6
作者：
Watabe T;Hosono M;Kinuya S;Yamada T;Yanagida S;Namba M;Nakamura Y
通讯作者：
Nakamura Y
影响因子：
1.6
作者：
Ikeda, Hayato;Hayashi, Yoshihiko;Hatazawa, Jun
通讯作者：
Hatazawa, Jun
影响因子：
7.5
作者：
Al-Ahmadie, Hikmat A.;Olgac, Semra;Reuter, Victor E.
通讯作者：
Reuter, Victor E.
影响因子：
2.3
作者：
Zalutsky MR;Pruszynski M
通讯作者：
Pruszynski M
DOI：
10.2967/jnumed.120.246363
发表时间：
2021-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Sprute K;Kramer V;Koerber SA;Meneses M;Fernandez R;Soza-Ried C;Eiber M;Weber WA;Rauscher I;Rahbar K;Schaefers M;Watabe T;Uemura M;Naka S;Nonomura N;Hatazawa J;Schwab C;Schütz V;Hohenfellner M;Holland-Letz T;Debus J;Kratochwil C;Amaral H;Choyke PL;Haberkorn U;Sandoval C;Giesel FL
通讯作者：
Giesel FL