Recombinant fragment of an antibody tailored for direct radioiodination

0378891 - ÚMG 2013 RIV GB eng J - Journal Article
Sedláček, Juraj - Fábry, Milan - Sieglová, Irena - Král, Vlastimil - Uhnáková, Bronislava - Mudra, M. - Kronrád, L. - Sawicka, A. - Mikolajczak, R. - Řezáčová, Pavlína
Recombinant fragment of an antibody tailored for direct radioiodination.
Journal of Labelled Compounds and Radiopharmaceuticals. Roč. 55, č. 1 (2012), s. 52-56. ISSN 0362-4803. E-ISSN 1099-1344
R&D Projects: GA MPO 2A-2TP1/076; GA MŠMT 1M0505
Institutional research plan: CEZ:AV0Z50520514
Keywords : I125 labelling * single-chain antibody variable fragment * tyrosine-rich polypeptide segment * fusion protein
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 1.240, year: 2012

High specific radioactivity (per mass or per mole) is an important and desirable parameter for the radiopharmaceuticals that are intended to target disease biomarker molecules. In direct radioiodination of immunoglobulins or their fragments, the predominant chemical reaction is usually the monoiodination of the phenol rings of tyrosine amino acid residues. For such radioiodination, the maximum achievable level of labeling of a given protein molecule obviously correlates to the number of solvent-accessible tyrosine residues. The grafting of proteins with additional iodine-acceptor tyrosine residues by conventional chemical techniques has been recently reported. We show here that a recombinant single chain variable fragment (scFv) of an anti-b-III-tubulin antibody, having a potential use in imaging neural lesions or astrocytoma and certain nonneuronal tumors, can be modified in a similar manner. However, in contrast to previously published examples, tyrosine residues are added to the polypeptide main chain without any chemical reaction, solely with molecular cloning and recombinant expression. Importantly, the tailoring outlined here is carried out ‘once and for all’ at laboratory scale (modifying permanently the expressed nucleic acid), whereas chemical indirect methods are necessarily carried out either at production scale or always before each round of radioiodination.
Permanent Link: http://hdl.handle.net/11104/0218862