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Published on: February 3, 2015
Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody
Vladimir Tolmachev1, Eskender Mume, Stefan Sjöberg
1Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Vladimir.Tolmachev@bms.uu.se
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.
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