PMID: 11312678Apr 21, 2001Paper

Renal metabolism of 3'-iodohippuryl N(epsilon)-maleoyl-L-lysine (HML)-conjugated Fab fragments

Bioconjugate Chemistry
Y FujiokaH Saji

Abstract

Renal localization of radiolabeled antibody fragments constitutes a problem in targeted imaging and radiotherapy. Recently, we reported use of a novel radioiodination reagent, 3'-[131I]iodohippuryl N(epsilon)-maleoyl-L-lysine (HML), that liberates m-iodohippuric acid before antibody fragments are incorporated into renal cells. In mice, HML-conjugated Fab demonstrated low renal radioactivity levels from early postinjection times. In this study, renal metabolism of HML-conjugated Fab fragments prepared by different thiolation chemistries and by direct radioiodination were investigated to determine the mechanisms responsible for the low renal radioactivity levels. Fab fragments were thiolated by 2-iminothiolane modification or by reduction of disulfide bonds in the Fab fragments, followed by conjugation with radioiodinated HML to prepare [131I]HML-IT-Fab and [125I]HML-Fab, respectively. In biodistribution studies in mice, both [131I]HML-IT-Fab and [125I]HML-Fab demonstrated significantly lower renal radioactivity levels than those of [125I]Fab. In subcellular distribution studies, [125I]Fab showed migration of radioactivity from the membrane to the lysosomal fraction of the renal cells from 10 to 30 min postinjection. On the other...Continue Reading

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Citations

Jun 5, 2002·Annals of Nuclear Medicine·Yasushi Arano
May 15, 2003·Nuclear Medicine and Biology·Tomoya UeharaYasushi Arano
Jan 7, 2003·Nature Medicine·Peter J Hudson, Christelle Souriau
Dec 1, 2001·Expert Opinion on Biological Therapy·P J Hudson, C Souriau
Mar 29, 2003·Expert Opinion on Biological Therapy·Christelle Souriau, Peter J Hudson
May 30, 2008·Advanced Drug Delivery Reviews·Hiromichi AkizawaYasushi Arano
Dec 28, 2016·European Journal of Nuclear Medicine and Molecular Imaging·Andreas JodalMartin Béhé
Apr 19, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tomoya UeharaYasushi Arano
Sep 21, 2007·Molecular Pharmaceutics·Olulanu H AinaKit S Lam

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