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Evaluation of technetium-99m-triamide-mercaptide complexes designed to identify properties favoring renal tubular
L Hansen1, L G Marzilli, D Eshima
1Department of Radiology, Emory University, Atlanta, Georgia.
Unlabelled:
To aid in the design of an improved 99mTc-labeled renal agent, several new [99mTcO(MAG3)]2- analogs were synthesized to determine the effects of varying the position and chemical form of the terminal charged group on renal clearance.
Methods:
Clearance, extraction efficiency and plasma protein binding were measured in six Sprague-Dawley rats per complex for ortho, meta and para isomers of [99mTcO(MAG2-ABA)]2-, with MAG2- = mercaptoacetylglycylglycyl- and ABA = aminobenzoate; [99mTcO(MAG2-pASA)]2-, with pASA = p-aminosalicylate; [99mTcO(MAG2-AMS]2-, with AMS = aminomethylsulfonate; and [99mTcO(MAG2-AMP]3-, with AMP = aminomethylphosphonate. For agents with relatively poor clearances, hepatobiliary excretion was evaluated by using a camera-based method.
Results:
The clearances of the ortho, meta and para isomers of [99mTcO(MAG2-ABA)]2- were 17%, 20% and 59% of those of OIH, respectively. The clearances of [99mTcO(MAG2-pASA)]2-, [99mTcO(MAG2-AMS)]2- and [99mTcO(MAG2-AMP)]3- were 32%, 46% and 39% those of OIH, respectively.
Conclusion:
Optimal tubular transport appears to require a terminal anionic group; a planar carboxylate is preferred over nonplanar -SO3- or -PO3(2-) substituents, suggesting that the smaller size and/or planar shape of the carboxylate group are probably more important than the total charge or charge distribution. Optimal transport also appears to depend on the oxo-carboxylate conformation (syn or anti) and the oxo-carboxylate distance, although these relationships can be modulated by steric interactions. These structure-distribution relationships are important factors to consider in the future design of renal radiopharmaceuticals.