Evaluation of technetium-99m-triamide-mercaptide complexes designed to identify properties favoring renal tubular transport.
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.


CONCLUSIONS
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.
Hansen
L
L
Department of Radiology, Emory University, Atlanta, Georgia.
Marzilli
L G
LG
Eshima
D
D
Malveaux
E J
EJ
Folks
R
R
Taylor
A
A
D000818:Animals; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D007684:Kidney Tubules / Q000000981:diagnostic imaging / Q000502:physiology*; D008956:Models, Chemical; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D017263:Technetium Tc 99m Mertiatide / Q000031:analogs & derivatives* / Q000737:chemistry
D017263:Technetium Tc 99m Mertiatide