In vivo comparison of CHX-DTPA ligand isomers in athymic mice bearing carcinoma xenografts.
In vivo comparison of CHX-DTPA ligand isomers in athymic mice bearing carcinoma xenografts.
复制标题
携带癌异种移植物的无胸腺小鼠中 CHX-DTPA 配体异构体的体内比较。
DOI：
10.1089/cbr.1999.14.209
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发表时间：
1999
影响因子：
3.4
通讯作者：
Schlom,J
中科院分区：
文献类型：
--
作者：
Roselli,M;Milenic,DE;Brechbiel,MW;Mirzadeh,S;Pippin,CG;Gansow,OA;Colcher,D;Schlom,J
通过金属螯合剂用放射性金属核素标记的单克隆抗体（MAb）正在实验室中进行研究，以用于临床试验。使用2-(对异硫氰酸苄基)-环己基-DTPA的两种异构体形式(CHX-A和CHX-B)的 111 In-和 88 Y-标记抗体(MAb B72.3)在带有LS-174T肿瘤、人结肠癌异种移植物的无胸腺小鼠中进行生物分布比较。将 CHX-(A 或 B)-125I-DTPA-B72.3 共同注射到所有无胸腺小鼠中，以评估螯合物缀合是否改变了 MAb B72.3 的特性。体外研究证明两种放射免疫缀合物均保持完整性和免疫反应性。然而，体内分析表明两种异构体形式之间存在重大差异。事实上，在7天的研究期间，88 Y-CHX-A-DTPA放射免疫缀合物表现出比CHX-B-DTPA螯合物缀合物更有效和稳定的肿瘤定位以及更慢的血液清除率，表明更高的体内稳定性。关键正常器官摄取方面的差异也很明显：当 CHX-A-DTPA 螯合物用铟或钇标记时，没有观察到肝脏和脾脏或骨与血液的比率显着增加。这里描述的结果表明，当放射性金属核素与 MAb 偶联时，CHX-A-DTPA 螯合物缀合物可以被认为比 CHX-B-DTPA 异构体形式更合适。
Monoclonal antibodies (MAbs) labeled with radiometallonuclides via metal chelators are being investigated in the laboratory for use in clinical trials. The biodistribution of111In- and88Y-labeled antibody (MAb B72.3) using two isomeric forms (CHX-A and CHX-B) of the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA was compared in athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. CHX-(A or B)-125I-DTPA-B72.3 was co-injected in all athymic mice to assess if the chelate conjugation altered the properties of MAb B72.3. In vitro studies demonstrated maintenance of integrity and immunoreactivity for both radioimmunoconjugates. The in vivo analysis, however, indicated major differences between the two isomer forms. In fact, the88Y-CHX-A-DTPA radioimmunoconjugate demonstrated over the 7-day study period, a more efficient and stable tumor localization as well as a slower blood clearance rate than the CHX-B-DTPA chelate conjugate, suggesting a greater in vivo stability. Differences were also evident in critical normal organ uptake: no significant increase in liver- and spleen- or bone-to-blood ratios was observed when the CHX-A-DTPA chelate was labeled with indium or yttrium. The results described here demonstrate that the CHX-A-DTPA chelate conjugate can be considered more suitable than the CHX-B-DTPA isomer form when radiometallonuclides are coupled to an MAb.