Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

0393378 - ÚJF 2014 RIV GB eng J - Journal Article
Bárta, P. - Lázníčková, A. - Lázníček, M. - Beckford, Denis R. - Beran, Miloš
Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor.
Journal of Labelled Compounds and Radiopharmaceuticals. Roč. 56, č. 5 (2013), s. 280-288. ISSN 0362-4803. E-ISSN 1099-1344
Grant - others:GA ČR(CZ) GAP304/10/1738
Institutional support: RVO:61389005
Keywords : radiopharmaceutical * 177Lu * 131I * nimotuzumab * EGFR * preclinical biodistribution
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 1.187, year: 2013

Background Radiolabelled monoclonal antibodies with affinity towards tumour-associated antigens may enhance the efficacy of cancer treatment with targeted radiotherapy. The humanized antibody nimotuzumab represents a promising vector to deliver radioactivity to tumours overexpressing epidermal growth factor receptor type 1 (ErbB1). We analysed the effect of radiolabelling nimotuzumab on its uptake in cancer cells and its biodistribution profile in preclinical experiments. Methods Nimotuzumab was labelled with 131I by oxidative iodination and with 177Lu using nimotuzumab conjugates with two different chelators (DTPA and DOTA) and two different spacers (p-SCN-Bn and NHS). For the receptor studies, two cell lines (HaCaT and A431) were used. Biodistribution studies were performed in male Wistar rats. Results The choice of radiolabel and the manner of its attachment to nimotuzumab had little effect on the internalization of the antibody into ErbB1-expressing cell lines. However, the type of radiolabel, the way in which it was attached to nimotuzumab and the radiolabelling procedure, significantly affected the blood clearance, liver uptake and liver persistence of radiolabelled nimotuzumab. 131I-nimotuzumab had the longest elimination half-life and the lowest radioactivity uptake in the liver. 177Lu-labelled nimotuzumab exhibited a shorter elimination half-life, high radioactivity and long-term retention in the liver.
Permanent Link: http://hdl.handle.net/11104/0222109