Journal
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
Volume 37, Issue 7, Pages 1397-1407Publisher
SPRINGER
DOI: 10.1007/s00259-010-1392-6
Keywords
Ga-68; PET imaging; Recombinant antibody fragments; EpCAM; HBED-CC
Funding
- Deutsche Krebshilfe
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Recombinant antibodies isolated from human antibody libraries have excellent affinities and high target specificity. As full-length IgGs are cleared inadequately slowly from the circulation, the aim of this work was to figure out which kind of recombinant antibody fragment proves to be appropriate for imaging epithelial cell adhesion molecule (EpCAM)-expressing tumours with the short-living radioisotope Ga-68. In order to combine the promising tumour targeting properties of antibodies with Ga-68, four antibody variants with the same specificity and origin only differing in molecular weight were constructed for comparison. Therefore, the binding domains of a single-chain fragment variable (scFv) isolated from a human na < ve antibody library were modified genetically to construct the respective full-length IgG, the tria- and diabody variants. These molecules were conjugated with the bifunctional chelating agent N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) to enable Ga-68 labelling at ambient temperature and compared in biodistribution and immuno-PET imaging experiments. The antibody variants with identical specificity proved to have the correct molecular weight, high binding affinity and specificity to their antigen, EpCAM. Radiometal complexation was efficiently performed at room temperature leading to Ga-68-labelled antibodies with unchanged binding properties compared to the original antibody variants. The best targeting properties were obtained with the scFv and especially with the diabody. The triabody showed higher absolute tumour uptake but only moderate clearance from circulation. The antibody variants differed considerably in normal organ uptake, clearance from circulation and tumour accumulation. The data demonstrate the feasibility of imaging solid tumours with the Ga-68-labelled diabody format. This type of recombinant protein might be a promising carrier even for the short-lived radiometal Ga-68 to support e.g. the management of immunotherapy which may provide important information regarding receptor expression of solid tumours.
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