Synthesis and evaluation of N/sub 2/S/sub 2/ complexes of Tc-99m as renal function agents

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6859305

Fritzberg, A R; Kasina, S; Eshima, D; Johnson, D L; Jones, A G; Lister-James, J; Davison, A; Brodack, J W

Complexes of Technetium-99m based on derivatives of the diamide disulfur ligand, N,N'-bis(mercaptoacetyl)ethylenediamine (DADS) have shown promise in clinical studies as a Tc-99m replacement for I-131 hippuran for renal function studies. However, problems of specificity, rate of renal excretion, and differences in behavior based on stereochemistry have caused them to be biologically inferior to hippuran. New ligands have been synthesized with the objectives of overcoming these disadvantages. In many cases stereoisomers resulted which were separated by HPLC and individually studied in animals. The parent Tc-99m DADS and amide carbonyl positional isomers including oxalyl and asymmetric showed that excretion rates and specificity were sensitive to these changes. Insertion of a hydroxymethylene group in the center ring gave chelate ring steroisomers, but both were rapidly excreted with high specificity. Methyl group addition to the center ring gave isomers that showed increased renal retention; 29% and 12% were found in the kidneys of mice at 10 min for the two products. Carboxylate group addition gave isomeric products with differences between isomers greater for center ring compared to side ring substitution. Extension of the carboxylate group to acetate as well as amide and glycine conjugation reduced isomer differences, but increased hepatobiliary excretion. Based on studies in mice and other species, several ligands appear promising and testing in humans is underway.

• Research Organization: Univ. of Utah, Salt Lake City, UT
• OSTI ID: 6859305
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
CHELATES
CHEMICAL PREPARATION
CHEMISTRY
CLEARANCE
COMPLEXES
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DRUGS
DYNAMIC FUNCTION STUDIES
EVALUATION
EXCRETION
FUNCTIONS
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOMERS
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOPHARMACEUTICALS
RETENTION FUNCTIONS
RODENTS
SCINTISCANNING
STEREOCHEMISTRY
SYNTHESIS
TECHNETIUM 99
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES