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

Journal Article · Fri Jul 01 04:00:00 EDT 1994 · Journal of Nuclear Medicine

OSTI ID:255213

Hansen, L; Marzilli, L G; Eshima, D ^[1]

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1. Emory Univ., Atlanta, GA (United States)

To aid in the design of an improved {sup 99m}Tc-labeled renal agent, several new [{sup 99m}TcO(MAG{sub 3})]{sup 2{minus}} analogs were synthesized to determine the effects of varying the position and chemical form of the terminal charged group on renal clearance. Clearance, extraction efficiency and plasma protein binding were measured in six Sprague-Dawley rats per complex for ortho, meta and para isomers of [{sup 99m}TcO(MAG{sub 2{minus}}ABA)]{sup 2{minus}}, with MAG{sub 2{minus}} = mercaptoacetylglycylglycyl- and ABA = aminobenzoate; [{sup 99m}TcO(MAG{sub 2{minus}}pASA)]{sup 2{minus}}, with pASA = p-aminosalicylate; [{sup 99m}TcO(MAG{sub 2{minus}}AMS)]{sup 3{minus}}, with AMP = aminomethylphosphonate. For agents with relatively poor clearances, hepatobiliary excretion was evaluated by using a camera-based method. The clearances of the ortho, meta and para isomers of [{sup 22m}TcO(MAG{sub 2{minus}}ABA)]{sup 2{minus}} were 17%, 20% and 59% of those of OIH, respectively. The clearances of [{sup 99m}TcO(MAG{sub 2{minus}}pASA)]{sup 2{minus}}, [{sup 99m}TcO(MAG{sub 2{minus}}AMS)]{sup 2{minus}} and [{sup 99m}TcO(MAG{sub 2{minus}}AMP)]{sup 3{minus}} were 32%, 46% and 39% those of OIH, respectively. Optimal tubular transport appears to require a terminal anionic group; a planar carboxylate is preferred over nonplanar -SO{sup {minus}}{sub 3} or -PO{sup 2{minus}}{sub 3} 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. 25 refs., 2 figs., 4 tabs.

• OSTI ID: 255213
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: 7 Vol. 35; ISSN 0161-5505; ISSN JNMEAQ
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
COMPARATIVE EVALUATIONS
RADIOPHARMACEUTICALS
RENAL CLEARANCE
TECHNETIUM 99
TECHNETIUM COMPLEXES