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Labeling of proteins with prechelated radionuclides

Thesis/Dissertation ·
OSTI ID:5545447
A number of ligands, some of which were bifunctional, containing pyrrole, phenol, or pyridine coordinating groups were synthesized. The radiochemistry of the complexes of the ligands with several radionuclides ({sup 105}Rh, {sup 109}Pd, {sup 99m}Tc, {sup 64}Cu,{sup 57}Cu, {sup 198}Au, {sup 111}In) was studied. Complexation of most of these radionuclides was accomplished by simple mixing of reagents without a need for any rigorous conditions, but rhodium complexes were prepared by refluxing in alcohol. Complex yields were determined by chromatography, adsorption on magnesium oxide or by solvent extraction. Conjugation of all the bifunctional complexes with human {gamma}-globulin was attempted by activating with thiophosgene and incubating at room temperature with the protein. Gel filtration chromatography was the main technique used for determining the conjugation yield. The stability of the coupled protein was studied by challenge experiments using EDTA and cyclam. High and stable conjugation yields were obtained with bifunctional complexes of most of the above radionuclides. The use of prechelated radionuclides for labeling proteins offer many advantages, most importantly, it reduces the nonspecific labeling and eliminates the exposure of the protein to too many harsh conditions normally needed for complexation and conjugation which frequently result in excessive denaturation of the labeled biomacromolecules. This technique provides an easy and efficient approach to the radionuclide labeling of other biologically active macromolecules such as antibody fragments.
Research Organization:
Missouri Univ., Columbia, MO (United States)
OSTI ID:
5545447
Country of Publication:
United States
Language:
English