Göhr-Rosenthal S, Schmitt-Willich H, Ebert W, Conrad J
Institute of Diagnostic Research GmbH, Schering AG, Berlin, Germany.
Invest Radiol. 1993 Sep;28(9):789-95.
The authors describe the magnetic resonance imaging (MRI) of a tumor in a nude mouse tumor model by means of an antibody-polylysine (Gd-DTPA) conjugate.
The monoclonal antibody, (MAB) RA96, was coupled to a polymeric gadolinium complex after periodate oxidation. This polymer, which consists of a polylysine backbone and complexing DTPA subunits, complexes an average of 65 gadolinium ions.
The immunoreactivity of the conjugates was reduced by an average of only 30% compared with the unbound MAB RA96. Biodistribution studies in nude mice with subcutaneously implanted human colon carcinomas (WiDr [specific] and HT29 [control]) revealed a tissue concentration in the specific tumor of 8.72% of the dose applied per gram despite the high molecular weight of the conjugates.
This tissue concentration is sufficient to achieve tumor-specific signal enhancement in the WiDr tumor on MRI. The problem of the high doses of protein required for MRI and possible solutions are discussed.
作者通过抗体 - 聚赖氨酸(钆 - 二乙三胺五乙酸,Gd - DTPA)偶联物描述了裸鼠肿瘤模型中肿瘤的磁共振成像(MRI)情况。
单克隆抗体(MAB)RA96在高碘酸盐氧化后与一种聚合钆络合物偶联。这种聚合物由聚赖氨酸主链和络合二乙三胺五乙酸亚基组成,平均络合65个钆离子。
与未结合的MAB RA96相比,偶联物的免疫反应性平均仅降低30%。在皮下植入人结肠癌(WiDr[特异性]和HT29[对照])的裸鼠中进行的生物分布研究显示,尽管偶联物分子量很高,但在特异性肿瘤中的组织浓度为每克应用剂量的8.72%。
这种组织浓度足以在MRI上实现WiDr肿瘤的肿瘤特异性信号增强。讨论了MRI所需高剂量蛋白质的问题及可能的解决方案。