Chelation of /sup 238/Pu(IV) in vivo by 3,4,3-LICAM(C): Effects of ligand methylation and pH

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · Health Phys.; (United States)

DOI:https://doi.org/10.1097/00004032-198906000-00002· OSTI ID:5873768

Durbin, P W; White, D L; Jeung, N L; Weitl, F L; Uhlir, L C; Jones, E S; Bruenger, F W; Raymond, K N

The linear tetracarboxycatecholate ligand, 3,4,3-LICAM(C) N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl-tetraaza tet radecane, tetra sodium salt) injected within 1 h after injection of Pu(IV) citrate, removes about the same fraction of Pu from animals as CaNa3-DTPA but removes less inhaled Pu than CaNa3-DTPA and leaves a Pu residue in the renal cortex. However, the formation constant of the expected Pu-3,4,3-LICAM(C) complexes are orders of magnitude greater than that of Pu-DTPA, and 3,4,3-LICAM(C) is 100 times more efficient than CaNa3-DTPA for removing Pu from transferrin in vitro. Because the formation constants of their actinide complexes are central to in vivo actinide chelation, ligand design strategies are dominated by the search for ligands with large Pu complex stabilities, and it was necessary to explain the failure of 3,4,3-LICAM(C) to achieve its thermodynamic potential in vivo. All the batches of 3,4,3-LICAM(C) prepared at Berkeley or in France (Euro-LICAM(C)) were found by high-pressure liquid chromatography to be mixtures of the pure ligand (55% in Berkeley preparations, 8.5% in Euro-LICAM(C)) and its four methylesters. A revised synthesis for 3,4,3-LICAM(C) is appended to this report. All of the incompletely hydrolyzed 3,4,3-LICAM(C) preparations and the pure ligand were tested for removal of Pu from mice (238Pu(IV) citrate intravenous, 30 mumol kg-1 of ligand at 1 h, kill at 24 h, radioanalyze tissues and separated excretal). The presence of methylesters did not significantly impair the ability of the ligands to remove Pu from mice, and it did not alter the fraction of injected Pu deposited in kidneys. Temporary elevation (reduction) of plasma and urine pH of mice by 0.5 mL of 0.1 M NaHCO3 (NH4Cl) injected before or simultaneously with pure 3,4,3-LICAM(C) somewhat improved (significantly reduced) Pu excretion but had little influence on Pu deposition in kidneys.

• Research Organization: Lawrence Berkeley Lab., CA (USA)
• OSTI ID: 5873768
• Journal Information: Health Phys.; (United States), Journal Name: Health Phys.; (United States) Vol. 56:6; ISSN HLTPA
• Country of Publication: United States
• Language: English

Related Subjects

560162* -- Radionuclide Effects
Kinetics
& Toxicology-- Animals
Plants
Microorganisms
& Cells
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTINIDE ISOTOPES
ACTINIDE NUCLEI
ALPHA DECAY RADIOISOTOPES
AMINES
ANIMALS
BODY
CHELATING AGENTS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CLEANING
COMPLEXES
DECONTAMINATION
EFFICIENCY
EVEN-EVEN NUCLEI
GLOBULINS
GLOBULINS-BETA
HEAVY NUCLEI
IN VIVO
ISOTOPES
KIDNEYS
LIGANDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METALLOPROTEINS
METHYLATION
MICE
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PLUTONIUM 238
PLUTONIUM ISOTOPES
PROTEINS
RADIOISOTOPES
RADIONUCLIDE KINETICS
REMOVAL
RODENTS
SEPARATION PROCESSES
SPERMIDINE
TRANSFERRIN
VERTEBRATES
YEARS LIVING RADIOISOTOPES