Tissue distribution properties of technetium-99m-diamide-dimercaptide complexes and potential use as renal radiopharmaceuticals

Journal Article · Wed Oct 01 04:00:00 EDT 1986 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00160a023· OSTI ID:7024070

Kasina, S; Fritzberg, A R; Johnson, D L; Eshima, D

A series of new ligands and the corresponding technetium-99m chelates based on diamide dimercaptide donor groups were synthesized as derivatives of technetium-99m 1,2-bis(2-thioacetamido)ethane, a complex shown to be excreted by renal tubular secretion. Chelation with 99mTc resulted in single radiochemical products or the expected numbers of stereoisomers. They were purified by high-performance liquid chromatography (HPLC) and evaluated in mice as potential renal tubular function agents. The in vivo properties were sensitive to the presence of functional groups, the positional isomerism of the carboxylate group functionality, and the chelate ring stereochemistry of the ligand. The presence of methyl groups slowed renal transit and decreased renal specificity. Cyclohexyl rings fused to the ethylene bridge of the center chelate ring decreased renal excretion while aromatic rings essentially abolished renal excretion. Slow hepatobiliary clearance was observed as an alternate mode of excretion. Polar groups, such as hydroxyl, carboxylate, and carboxamide, increased renal excretion rates and specificity in a stereochemically dependent manner. 99mTc chelates of 1,3-bis(2-thioacetamido)-2-hydroxypropane, 3,4-bis(2-thioacetamido)butanoate and 1,8-dimercapto-2,7-dioxo-3,6-diazanonanoate were identified as promising new renal radiopharmaceuticals.

• Research Organization: Univ. of Utah, Salt Lake City
• OSTI ID: 7024070
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 10; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400702 -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMIDES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CHALCOGENIDES
CHEMICAL PREPARATION
CHEMISTRY
CLEARANCE
DIAGNOSTIC USES
DISTRIBUTION
DRUGS
EXCRETION
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIOCHEMISTRY
RADIOISOTOPES
RADIOPHARMACEUTICALS
RENAL CLEARANCE
RODENTS
SULFIDES
SULFUR COMPOUNDS
SYNTHESIS
TECHNETIUM 99
TECHNETIUM ISOTOPES
TISSUE DISTRIBUTION
USES
VERTEBRATES
YEARS LIVING RADIOISOTOPES