Influence of radiolabel on the in vivo processing of intact and fragmented anti-tumour monoclonal antibody.

A Smith, R Alberto, P A Shubiger
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Abstract

The anti-colon carcinoma MoAb35 and its F(ab')2 fragment were labelled with 131I or 67Cu and their biodistributions compared in nude mice bearing human tumour xenografts. Two-fold higher levels of 67Cu were found in the xenografts than 131I, with no significant difference in whole-body distribution. For the F(ab')2 fragment tumour levels were not significantly different between 131I and 67Cu. A very high accumulation of 67Cu was found in the kidney (36.7% ID/g). Whether deiodination in the kidney could account for the difference in nuclide accumulation was checked by repeating the study with 131I, linked to the F(ab')2 by a method known to resist deiodination. The results showed a slight increase in tumour accumulation of 131I but kidney levels remained low at 3.1% ID/g 24 hours post-injection compared to 42.4% ID/g for 67Cu, suggesting that deiodination does not play a role in the observed low levels of 131I in the kidney. Ongoing studies on the distribution and processing of radioimmunoconjugates will hopefully assist in their application in clinical studies.

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放射性标记对完整和碎片化抗肿瘤单克隆抗体体内加工的影响。
用131I或67Cu标记抗结肠癌MoAb35及其F(ab’)2片段,比较其在移植人肿瘤裸鼠体内的生物分布。67Cu在异种移植物中的含量比131I高2倍,但在全身分布上无显著差异。对于F(ab’)2片段,肿瘤水平在131I和67Cu之间无显著差异。肾脏中67Cu含量非常高(36.7% ID/g)。肾脏中的去碘是否可以解释核素积累的差异,通过与131I重复研究来验证,131I通过一种已知的抵抗去碘的方法与F(ab')2相连。结果显示,131I的肿瘤积累略有增加,但肾脏水平仍然很低,注射后24小时为3.1% ID/g,而67Cu为42.4% ID/g,这表明脱碘作用对肾脏中观察到的低水平131I没有作用。对放射免疫偶联物的分布和加工的研究将有助于其在临床研究中的应用。
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