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The Quarterly Journal of Nuclear Medicine 1998 December;42(4):262-70

Copyright © 2000 EDIZIONI MINERVA MEDICA

language: English

Strategies to reduce renal radioactivity levels of antibody fragments

Arano Y.

From the Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences Kyoto University, Sakyo-ku, Kyoto, Japan


FULL TEXT  


Antibody frag­ments ­such as Fab and sin­gle-­chain Fv frag­ments pos­sess ­many advan­tag­es ­over ­intact anti­bod­ies as vehi­cles to deliv­er radio­ac­tiv­ity for diag­nos­tic and ther­a­peu­tic appli­ca­tions. However, radio­lab­eled anti­body frag­ments exhib­it­ed ­high and per­sis­tent local­iza­tion of the radio­ac­tiv­ity in the kid­ney, ­which com­pro­mis­es diag­nos­tic accu­ra­cy and ther­a­peu­tic effec­tive­ness. Recent stud­ies indi­cat­ed ­that the per­sis­tent local­iza­tion of ­renal radio­ac­tiv­ity ­would be orig­i­nat­ed ­from the re-ab­sorp­tion of glo­mer­u­lar­ly-fil­tered radio­lab­eled anti­body frag­ments, fol­lowed by the reten­tion of the radio­me­tab­olites gen­er­at­ed ­after deg­ra­da­tion in the lyso­so­mal com­part­ment of the ­renal ­cells. Two ­major approach­es ­have ­been per­formed to ­reduce the ­renal radio­ac­tiv­ity lev­els of anti­body frag­ments. One is to ­block the reab­sorp­tion of radio­lab­eled anti­body frag­ments them­selves at the prox­i­mal tubu­lar ­cells ­from the lumi­nal ­fluid by admin­is­tra­tion of ­basic ami­no ­acids ­such as L-­lysine. The oth­er ­approach is to ­decrease the res­i­dence ­time of the radio­me­tab­olites with­in the lyso­so­mal com­part­ments of the ­renal ­cells by intro­duc­ing a cleav­able link­age ­between anti­body frag­ments and radio­me­tab­olites of rap­id uri­nary excre­tion. Another ­approach to ­reduce ­renal radio­ac­tiv­ity lev­els of anti­body frag­ments may be to ­release radio­lab­eled com­pound of uri­nary excre­tion ­from glo­mer­u­lar­ly-fil­tered anti­body frag­ments ­before ­they are reab­sorbed ­into the ­renal ­cells by the ­action of ­brush bor­der ­enzymes ­present on the ­lumen of the ­renal prox­i­mal ­cells. In ­this ­paper, ­recent stud­ies of the ­three approach­es to ­reduce the ­renal radio­ac­tiv­ity lev­els of anti­body frag­ments are brief­ly ­reviewed.

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