Radiolabeling proteins with bifunctional chelating agents
The high specific binding ability of a monoclonal antibody for its antigen is of great interest in targeting cancer cells. The conjugation of radioactive nuclides to monoclonal antibodies results in agents for radiotherapy and other medical applications. The authors are interested in radionuclides having moderate beta energies and half-lives of 0.5 to 3 days such as Tc-99m, Rh-105, Pd-109, and Au-198. Stable conjugates of these metal ions with monoclonal antibodies might provide high efficiency in killing cancer cells and low radiation damage to the nontarget cells. This work focuses on the design and synthesis of bifunctional chelating agents for these metal ions suitable for antibody labeling. The ligands are aromatic Schiff bases with phenylenediamine as the backbone and with a second chemically active functional group attached to the benzene ring. This second functional group allows stable attachment of radioactive metal ion complexes to the antibody through chemical bonding. Based on this idea, some bifunctional ligands such as N,N[prime]-bis(2-hydroxy-phenylmethylidene)-3,4-diamino benzoic acid and its reduced form bis(2-hydroxyphenylmethyl)-3,4-diaminobenzoic acid have been synthesized. The studies show that stable complexes of Tc-99m, Pd-109, and Rh-105 can be prepared using these ligands, especially the reduced form. Complexation yields of 95%, 90%, and 80% are obtained for Tc-99m, Pd-109, and Rh-105, respectively, using the reduced form of the ligand. Human gamma globulin was used as a model protein for the antibody labeling. The labeling yields for Tc-99m, Pd-109, and Rh-105 were about 60%, 70%, and 65%, respectively, based on gel permeation chromatography.
- Research Organization:
- Missouri Univ., Columbia, MO (United States)
- OSTI ID:
- 7165643
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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(Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents)
Bifunctional chelates of Rh-105 and Au-199 as potential radiotherapeutic agents
Related Subjects
CHELATING AGENTS
CHEMICAL PREPARATION
LABELLED COMPOUNDS
MONOCLONAL ANTIBODIES
LABELLING
PROTEINS
RADIOPHARMACEUTICALS
PALLADIUM 109
POLYCYCLIC AROMATIC AMINES
RHODIUM 105
SCHIFF BASES
TECHNETIUM 99
AMINES
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DRUGS
EVEN-ODD NUCLEI
HOURS LIVING RADIOISOTOPES
IMINES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PALLADIUM ISOTOPES
RADIOISOTOPES
RHODIUM ISOTOPES
SECONDS LIVING RADIOISO
SYNTHESIS
TECHNETIUM ISOTOPES
YEARS LIVING RADIOI
400703* - Radiochemistry & Nuclear Chemistry- Radioisotope Production