Abstract:
:The high uptake and prolonged renal retention of monoclonal antibody fragments that are conjugated with radiometal chelates precludes their routine clinical use due to high background counts, which may hinder detection of nearby lesions and/or cause renal radiotoxicity. We report on the potential use of Lys as a pharmacological agent to enhance renal excretion of the [177Lu]alpha-[2-(4-aminophenyl) ethyl]-1,4,7,10-tetraaza-cyclodecane-1,4,7,10-tetraacetic acid CC49 Fab ([177Lu]CC49 Fab) radioimmunoconjugate. The monoclonal antibody portion of this complex is directed toward the tumor-associated glycoprotein-72 antigen. Lys was administered to female BALB/c mice by i.p. injections. [177Lu]CC49 Fab bolus injections were given by the i.v. route. Results of our investigations showed that: (a) kidney radioactivity concentrations were inversely related to Lys dose. The optimal dose (50 mg/mouse) evoked a 3-fold reduction in kidney counts; (b) Lys was most effective when injected 15 min before, or at the same time as, [177Lu]CC49 Fab; (c) the renal effect was both rapid (3-fold decrease at 15 min after injection) and prolonged (4-fold decrease at 24 h after injection); (d) a single Lys dose decreased total body radioactivity by > 2.5-fold; (e) urine excretion of radioactivity was enhanced in Lys-treated mice. High pressure liquid chromatographic analyses using a GF-250 column showed that a large fraction of this urine radioactivity coeluted with a [177Lu]CC49 Fab injection standard. We conclude that Lys enhances the urinary excretion of radioactivity associated with [177Lu]CC49 Fab. These observations warrant further study with regard to the use of amino acids or their derivatives as pharmacological agents to enhance the urinary excretion of small-molecule radioimmunoconjugates.
journal_name
Cancer Resjournal_title
Cancer researchauthors
DePalatis LR,Frazier KA,Cheng RC,Kotite NJsubject
Has Abstractpub_date
1995-11-15 00:00:00pages
5288-95issue
22eissn
0008-5472issn
1538-7445journal_volume
55pub_type
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