Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding
2009 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 36, no 4, 692-701 p.Article in journal (Refereed) Published
PURPOSE: HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule Z(HER2:342) is a small (7 kDa) affinity protein binding to HER2 with an affinity of 22 pM. The goal of this study was to evaluate the use of ((4-hydroxyphenyl)ethyl)maleimide (HPEM) for radioiodination of Z(HER2:342) and to compare the targeting properties of monomeric and dimeric forms of Z(HER2:342). METHODS: The biodistribution of different radioiodinated derivatives of Z(HER2:342) was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of (125)I-PIB-Z(HER2:342) and site-specifically labelled (125)I-HPEM-Z(HER2:342)-C were compared. Biodistributions of monomeric (131)I-HPEM-Z(HER2:342)-C and dimeric (125)I-HPEM-(Z(HER2:342))(2)-C were evaluated using a paired-label method. RESULTS: (125)I-HPEM-Z(HER2:342)-C had the same level of tumour accumulation as (125)I-PIB-Z(HER2:342), but fourfold lower renal retention of radioactivity. The monomeric form of Z(HER2:342) provided better tumour targeting than the dimeric form. CONCLUSION: Favourable biodistribution of (131)I-HPEM-Z(HER2:342)-C makes it a promising candidate for radionuclide therapy.
Place, publisher, year, edition, pages
2009. Vol. 36, no 4, 692-701 p.
Affibody molecule, HER2, Renal uptake, Iodine-131, Radionuclide therapy
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-104569DOI: 10.1007/s00259-008-1003-yISI: 000264101400018PubMedID: 19066886OAI: oai:DiVA.org:uu-104569DiVA: diva2:219951