Larsen R H, Hoff P, Vergote I B, Bruland O S, Aas M, De Vos L, Nustad K
Department of Chemistry, University of Oslo, Norway.
Gynecol Oncol. 1995 Apr;57(1):9-15. doi: 10.1006/gyno.1995.1093.
Four different chemical forms of the alpha-particle emitting radionuclide 211At were injected intraperitoneally in mice inoculated intraperitoneally 30 hr in advance with 10(6) cells of the K13 murine hybridoma cell line. The different 211At forms were (a) free 211At, (b) 211At-labeled TP-3 nonspecific monoclonal antibody (211At-TP-3), (c) 211At-labeled human IgG kappa (211At-hIgG kappa), and (d) 211At-labeled monodisperse polymer particles (211At-MDPP). A significantly prolonged survival (P < 0.05) was observed with injected doses down to 7 kBq for the 211At-MDPP, and down to 25 kBq for 211At-hIgG kappa. There were no significant differences in survival between 211At-MDPP, 211At-hIgG kappa, and 211At-TP-3 at the dose level of 200 kBq. The group receiving 250 kBq free 211At per animal had a shorter survival than the three other forms at 200 kBq. The groups treated with 500, 200, and 65 kBq 211At-MDPP had a similar survival. The group given the highest dose of 211At-hIgG kappa (275 kBq) had the highest fraction (50%) of long-term survivors of all groups. Biodistribution measurements and total body scintigrams in mice without tumor revealed that the free 211At was distributed all over the body within 10 min after injection while at 2 hr a high fraction of the 211At-TP-3 and 211At-hIgG kappa was still present intraperitoneally. In conclusion this study indicates that 211At-labeled MDPP and 211At-labeled IgG's may be efficient tools for treatment of intraperitoneal superficial tumor cells and malignant ascites.
在预先经腹腔接种10⁶个K13小鼠杂交瘤细胞系细胞30小时的小鼠中，将发射α粒子的放射性核素²¹¹At的四种不同化学形式经腹腔注射。不同的²¹¹At形式为：(a) 游离²¹¹At，(b) ²¹¹At标记的TP-3非特异性单克隆抗体(²¹¹At-TP-3)，(c) ²¹¹At标记的人IgG κ(²¹¹At-hIgG κ)，以及(d) ²¹¹At标记的单分散聚合物颗粒(²¹¹At-MDPP)。对于²¹¹At-MDPP，注射剂量低至7 kBq时观察到生存期显著延长(P<0.05)，对于²¹¹At-hIgG κ，低至25 kBq时生存期显著延长。在200 kBq剂量水平下，²¹¹At-MDPP、²¹¹At-hIgG κ和²¹¹At-TP-3之间的生存期无显著差异。每只动物接受250 kBq游离²¹¹At的组比接受200 kBq的其他三种形式的生存期短。接受500、200和65 kBq ²¹¹At-MDPP治疗的组生存期相似。给予最高剂量²¹¹At-hIgG κ(275 kBq)的组在所有组中具有最高比例(50%)的长期存活者。对无肿瘤小鼠的生物分布测量和全身闪烁扫描显示，游离²¹¹At在注射后10分钟内遍布全身，而在2小时时，²¹¹At-TP-3和²¹¹At-hIgG κ的很大一部分仍存在于腹腔内。总之，本研究表明²¹¹At标记的MDPP和²¹¹At标记的IgG可能是治疗腹腔浅表肿瘤细胞和恶性腹水的有效工具。
