Bifunctional chelating agents (BCAs) are required to complex radiometals to biomolecules such as proteins and peptides. Copper-64 (B+, T1~ = 12.8 h) has shown potential as a therapeutic and diagnostic radiometal and macrocyclic BCAs are necessary for in vivo stability. 1A3 and 1A3-F(ab')2 are anticolorectal MAbs that have been labeled with 64Cu using the bifunctional chelate. 6-bromoacetamidobenzyl-1 ,4,8,11 - tetraazacyclotetradecane-I ,4,8,11 -tetraacetic acid (BAT), and evaluated In rat and hamster models.(2) 64Cu-BAT-1A3 and 64cu-BAT-1A3-F(ab')2 had superior tumor uptake In a hamster model than either the 111In- or 1251-labeled antibodies; however, the kidney uptake of 64Cu.BAT.1A3.F(ab')2 was high. The bifunctional chelate, 4-[(I ,4,8,11-tetraazacyclotetradec-1-yl)-methyl]benzoic acid (CPTA), has been previously conjugated to 1A3 and 1A3-F(ab')2, labeled with copper, and compared to the BAT conjugates in both rats and hamsters.(3) In this study, we have synthesized BAT, CPTA, 6-isothiocyanatobenzyl- 1,4,8,11 - tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (SCN-TETA) and 4-[(I ,4,7,10,13-pentaazacyclopentadec-1-yl)-methyl]benzoic acid (PCBA) for conjugatlon to 1A3 and 1A3-F(ab')2 and radiolabeling with copper isotopes. The four bifunctional chelates (Figure 1), when conjugated to 1A3 and 1A3-F(ab')2 and labeled with 64Cu. are compared with respect to their biodistribution in rats and hamsters. The metabolism of the SCN-TETA. CPTA, and PCBA conjugates in Sprague-Dawley rats will also be discussed.
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