Koziol J A, Lee P P, Dillman R O, Fagnani R, Halpern S E
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Nucl Med Commun. 1995 Apr;16(4):299-305. doi: 10.1097/00006231-199504000-00162.
Radiolabelled anti-tumour antibodies, their fragments and derivatives hold promise for imaging and therapeutics in oncology. A better understanding of the pharmacokinetics of these entities is therefore important for clinical applications and management. In the present study, the in vivo behaviour of 111Indium-labelled monoclonal anti-CEA antibody ZCE-025 and its F(ab')2 and Fab' fragments and a Fab' derivative are compared in the nude mouse-human tumour model. The object of the derivative was to improve the tumour uptake of the fragment yet reduce its high renal uptake while continuing to achieve desirable kinetics in the normal tissues. Uptake of the derivative in the tumour was comparable to that of the intact antibody and exceeded that of the underivatized fragments. Moreover, uptake in non-target tissues was lower with the derivative than with the intact entity. The renal uptake of the derivative was dramatically lower than for the fragments. The modelling data strongly suggest that the derivatives will be advantageous for clinical use compared with the underivatized whole antibodies or their fragments.
放射性标记的抗肿瘤抗体、其片段及衍生物在肿瘤学的成像和治疗方面具有前景。因此，更好地了解这些物质的药代动力学对于临床应用和管理至关重要。在本研究中，在裸鼠-人肿瘤模型中比较了111铟标记的单克隆抗癌胚抗原抗体ZCE-025及其F(ab')2和Fab'片段以及一种Fab'衍生物的体内行为。该衍生物的目的是提高片段的肿瘤摄取量，同时降低其高肾摄取量，同时在正常组织中继续实现理想的动力学。该衍生物在肿瘤中的摄取与完整抗体相当，且超过了未衍生化片段的摄取。此外，该衍生物在非靶组织中的摄取低于完整物质。该衍生物的肾摄取量明显低于片段。建模数据有力地表明，与未衍生化的完整抗体或其片段相比，该衍生物在临床应用中将具有优势。
