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A Journal on Nuclear Medicine and Molecular Imaging
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  NOVEL METHODS OF ALTERING PHARMACOKINETICS IN RADIOPHARMACEUTICAL DESIGN
Guest Editor: Hnatowich D.
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The Quarterly Journal of Nuclear Medicine 2002 September;46(3):206-23

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Altering pharmacokinetics of radiolabeled antibodies by the interposition of metabolizable linkages. Metabolizable linkers and pharmacokinetics of monoclonal antibodies

Akizawa H. 1, Arano Y. 2

1 Faculty of Pharmaceutical Sciences, Okayama University, Okayama 2 Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan


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Mono­clonal anti­bodies, ­their frag­ments and low molec­ular ­weight onco­philic mole­cules ­such as syn­thetic som­a­tos­tatin deriv­a­tives ­have ­been ­used to ­deliver radio­ac­tivity to ­target ­cells for ­both diag­nostic and ther­a­peutic pur­poses. Clin­ical ­studies dem­on­strated ­high abil­ities of the radio­lab­eled anti­bodies and pep­tides for ­nuclear med­i­cine appli­ca­tions. How­ever, ­high and per­sis­tent local­iza­tion of radio­ac­tivity was ­observed in the ­liver or ­kidney espe­cially ­when ­these mole­cules are ­labeled ­with ­metallic radio­nu­clides, ­which ­reduce diag­nostic accu­racy and com­pro­mise ther­a­peutic effec­tive­ness. ­Thus, radio­lab­eled anti­bodies and pep­tides ­would ­become ­much ­more ­useful in ­both tar­geted ­imaging and radio­therapy if the unde­sir­able radio­ac­tivity local­iza­tion can be dimin­ished. As a ­means to ­reduce the unde­sir­able radio­ac­tivity, inter­po­si­tion of a metab­o­liz­able ­linkage ­between an anti­body and a radio­label was pro­posed to gen­erate radio­lab­eled ­small mole­cules of uri­nary excre­tion ­from the ­parental anti­body by enzy­matic ­cleavage of the ­linkage. In ­this ­paper, ­after indi­cating the ratio­nale ­behind the radio­phar­ma­ceu­tical ­design, a sig­nif­i­cant ­role ­played by the inter­po­si­tion of the metab­o­liz­able ­linkage in ­altering phar­ma­cok­i­netics of radio­lab­eled anti­bodies is ­described ­from a ­variety of ­studies so far ­reported ­with an ­emphasis ­being ­laid on the impor­tance of radio­me­tab­olite-­based ­design of metab­o­liz­able link­ages.

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