Correlating labeling chemistry and in-vitro test results with the biological behavior of radiolabeled proteins.
A study of the effect of various rediochemical labeling parameters on the in-vivo behavior of proteins, in particular of monoclonal antibodies, was carried out. Both radioiodination, and radiometal labeling (using protein-chelating agent conjugates), of antimelanoma, antiplatelet, and anticolon carcinoma monoclonal antibodies (222.28s, 7E3, and GA-733 respectively), as well as the direct labeling of human serum albumin with 99mTc, were investigated. Different aspects of the biological behavior are affected in relation to the labeling chemistry involved. These include the immunoreactivity, blood clearance and tissue uptake kinetics, and rates and routes of excretion. Individual radionuclide effects have often to be addressed separately. Some antibodies are more susceptible to alteration from labeling conditions than others. Careful optimization of labeling and purification procedures is thus necessary for particular radionuclide/antibody combinations in order to obtain predictable and reproducible in-vivo results for both immunoscintigraphy and immunotherapy applications.
Medical Department, Brookhaven National Laboratory, Upton, New York.
S C
SC
Srivastava
G E
GE
Meinken
D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology; D004285:Dogs; D006801:Humans; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008819:Mice, Nude
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes