Differential metabolic patterns of iodinated versus radiometal chelated anticarcinoma single-chain Fv molecules.

摘要: Genetically engineered single-chain Fvs (sFv) are defined as recombinant proteins composed of a variable light chain amino acid sequence an immunoglobulin tethered to heavy by designed peptide. Previous studies using iodine-labeled sFv, derived from the anticarcinoma monoclonal antibody CC49, showed that 125I-sFv could efficiently target antigen-positive tumors in human tumor xenograft model while demonstrating rapid plasma clearance and minimal uptake normal organs. One issues we raised analysis iodinated sFv metabolic was whether similar patterns would be observed if were labeled with radiometal. In reported here, 125I-CC49 177Lu-CC49 coinjected mice bearing carcinoma xenografts. Both forms targeting pharmacokinetics. The 177Lu-sFv, however, greater liver spleen much higher kidney. These thus demonstrate despite their small size ( M r 27,000), metal-chelated shows pattern very different than which is most likely due retention metal organs metabolizing sFv.