L. Hansen et al., EVALUATION OF TECHNETIUM-99M-TRIAMIDE-MERCAPTIDE COMPLEXES DESIGNED TO IDENTIFY PROPERTIES FAVORING RENAL TUBULAR TRANSPORT, The Journal of nuclear medicine, 35(7), 1994, pp. 1198-1205
To aid in the design of an improved Tc-99m-labeled renal agent, severa
l new [(TcO)-Tc-99m(MAG,)](2-) analogs were synthesized to determine t
he effects of varying the position and chemical form of the terminal c
harged group on renal clearance. Methods: Clearance, extraction effici
ency and plasma protein binding were measured in six Sprague-Dawley ra
ts per complex for ortho, meta and para isomers of [(TcO)-Tc-99m(MAG(2
)-ABA)](2-), with MAG(2)- = mercaptoacetylglycylglycyl- and ABA = amin
obenzoate; [(TcO)-Tc-99m(MAG(2)-pASA)](2-), with pASA = p-aminosalicyl
ate; [(TCO)-T-99m(MAG(2)-AMS](2-), With AMS = aminomethylsulfonate; an
d [(TCO)-T-99m(MAG(2)-AMp](3-), With AMp = aminomethylphosphonate. For
agents with relatively poor clearances, hepatobiliary excretion was e
valuated by using a camera-based method. Results: The clearances of th
e ortho, meta and para isomers of [(TcO)-Tc-99m(MAG(2)-ABA)](2-) were
17%, 20% and 59% of those of OIH, respectively. The clearances of [(TC
O)-T-99m(MAG(2)-pASA)](2-), [(TCO)-T-99m(MAG(2)-AMS)](2-) and [(TcO)-T
c-99m(MAG(2)-AMP)](3-) were 32%, 46% and 39% those of OIH, respectivel
y. Conclusion: Optimal tubular transport appears to require a terminal
anionic group; a planar carboxylate is preferred over nonplanar -SO3-
or -PO32- substituents, suggesting that the smaller size and/or plana
r 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 i
mportant factors to consider in the future design of renal radiopharma
ceuticals.