Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules.
OBJECTIVE
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.


CONCLUSIONS
Favourable biodistribution of (131)I-HPEM-Z(HER2:342)-C makes it a promising candidate for radionuclide therapy.
Tolmachev
Vladimir
V
Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Vladimir.Tolmachev@bms.uu.se
Mume
Eskender
E
Sjöberg
Stefan
S
Frejd
Fredrik Y
FY
Orlova
Anna
A
D000818:Animals; D045744:Cell Line, Tumor; D019281:Dimerization; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D007668:Kidney / Q000000981:diagnostic imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases