作者: M W Brechbiel , W C Eckelman , J A Carrasquillo , L Lang , E Jagoda
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摘要: Monoclonal antibodies (MoAbs) were proposed as candidates for selective tumor targeting based on their high binding affinity tumors and the absence of by normal tissue. However, exclusive complete transport drug have been found lacking in use intact MoAbs, especially case solid tumors. Smaller fragments that maintained desiderable characteristics appear to an advantage because increase whole body clearance shorter time maximum target non-target ratio. But tissue increases molecular weight or size decreases, kidney, glomerular sieving coefficient increases. We used two approaches overcome binding: a) lysine block uptake Low Molecular Weight Proteins (LMWP) proximal tubules b) labeling different amino acids LMWP alter residence kidney. The combination these methods, blocking with shortening radioactive compound produced can lead substantially decreased kidney targeting. paradigm was effectively demonstrated using 18F-labeled anti-Tac dsFv. Shortening illustred comparing kinetics catabolite versus methionine metabolite. Furthermore, rapid pharmacokinetics are consistent half-lives PET radionuclides concomitant quantitation sensitivity afforded PET.