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  • Title: Yttrium-90 chelation properties of tetraazatetraacetic acid macrocycles, diethylenetriaminepentaacetic acid analogues, and a novel terpyridine acyclic chelator.
    Author: Stimmel JB, Stockstill ME, Kull FC.
    Journal: Bioconjug Chem; 1995; 6(2):219-25. PubMed ID: 7599265.
    Abstract:
    Realization of the potential of yttrium-90 for the radioimmunotherapy of cancer depends on rapid and kinetically stable chelation. Conditions were evaluated that influenced the chelation efficiency of these select chelators for yttrium-90: the macrocyclic chelators 2-(rho-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tet raacetic acid (nitro-DOTA); alpha-(2-(rho-nitrophenyl)ethyl)-1,4,7,10,- tetraazacyclododecane-1-acetic-4,7,10-tris(methylacetic) acid (nitro-PADOTA); 2-(rho-nitrobenzyl)-1,4,7,10-tetraazacyclotridecane- N,N',N",N"'-tetraacetic acid (nitro-TRITA); the acyclic chelator diethylenetriaminepentaacetic acid (DTPA); its analogues N-[2-amino-3-(rho-nitrophenyl)propyl]-trans- cyclohexane-1,2-diamine-N,N',N"-pentaacetic acid (nitro-CHX-A-DTPA) and 2-methyl-6-(rho-nitrobenzyl)-1,4,7- triazaheptane-N,N,N',N",N"-pentaacetic acid (nitro-1B4M-DTPA or nitro-MX-DTPA); and a novel acyclic terpyridine chelator, 6,6"-bis[[N,N,N",N"- tetra(carboxymethyl)amino]methyl]-4'-(3-amino-4-methoxyphenyl)-2,2':6',2 "- terpyridine (TMT-amine). The chelators fell into two distinct classes. The acyclic chelators, DTPA, nitro-CHX-A-DTPA, nitro-MX-DTPA, and TMT-amine, chelated instantaneously in a concentration-independent manner. Chelation efficiency was affected minimally when the concentrations of trace metal contaminants were increased. In contrast, the macrocyclic chelators, nitro-DOTA, nitro-TRITA, and nitro-PADOTA, chelated yttrium-90 more slowly in a concentration-dependent manner where efficiency was maximal only when the chelator:metal ratio was greater than 3. Their chelation efficiency diminished in a concentration-dependent fashion as the concentrations of trace metal contaminants were increased. Optimum labeling efficiencies were obtained through application of these principles.(ABSTRACT TRUNCATED AT 250 WORDS)
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