Metal complexes of tetradentate nitrogen ligands as bifunctional chelates for radiolabeling of proteins

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1985

OSTI ID:6942780

Chen, F M

Several tetradentate nitrogen ligands were synthesized. The chemistry and radiochemistry of these ligands as well as their complexes with Pd-109, Cu-64 and Tc-99m were studied. Two of the ligands are bifunctional chelating agents which were used to prepare radioactive metal complexes for protein (HSA and IgG) labeling. The ligand, 5,7-dioxo-1,4,8,11-tetraazaundecane (DOTU), was reacted with Pd(II) to produce a neutral complex. The bifunctional ligand 6-(5'-charboxylpentyl)-5,7-dioxo-1,4,8,11-tetraazaundecane (DOTU-C/sub 5/COOH), was complexed with Pd-109(II) in the same manner. It was then purified and conjugated to the protein by a carbodiimide coupling method. These DOTU ligands were also complexed with Tc-99m. A mixture of Tc-99m-DOTU-C/sub 5/COOH and Pd-109-DOTU-C/sub 5/COOH was used to dual label the protein (HSA). It was found that the protein was dually labeled with Pd-109 and Tc-99m, both in approx.30% yield. Another group of bifunctional ligands was based on 6-(5'-aminopentyl)-1,4,8,11-tetraazaundecane (APTU, a pentaamine). Complexes of this ligand with Tc-99m and Cu-64 were studied. It may still be possible to use this complex, even though the yield is low, because the Tc-99m can be produced in high specific activity and other, more efficient, coupling methods are available. The complex of Cu-64-APTU was prepared and conjugated to the protein in approx.6% yield by procedures similar to those used for Tc-99m labeling. Exchange experiments with EDTA indicate that complexes are labile suggesting that Cu-64-APTU conjugated protein may not be stable in vivo due to the disassociation of the Cu-64 and the transchelation in blood. It should be possible, however, to improve the complex stability by derivatization of the ligand.

• Research Organization: Missouri Univ., Columbia (USA)
• OSTI ID: 6942780
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
AMINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CHELATING AGENTS
COPPER 64
COPPER ISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
GLOBULINS
HOURS LIVING RADIOISOTOPES
IMMUNOGLOBULINS
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LABELLING
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PALLADIUM 109
PALLADIUM ISOTOPES
PROTEINS
RADIOISOTOPES
TECHNETIUM 99
TECHNETIUM ISOTOPES
TRACER TECHNIQUES
YEARS LIVING RADIOISOTOPES