Labeling of monoclonal antibodies with a 67Ga-phenolic aminocarboxylic acid chelate. Part II. Comparison of immunoreactivity and biodistribution of monoclonal antibodies labeled with the 67Ga-chelate or with 131I.
Coupling of the 67Ga-P-EDDHA chelate via carbodiimide to the anti-melanoma monoclonal antibody (Mab) M.2.9.4 resulted in a low degree of oligomerization, but a considerable degree of intra-molecular (inter-chain) cross-linking. However, this did not impair immunoreactivity, nor did the half-life in vivo differ substantially from that of 131I-M.2.9.4. Biodistribution analysis in normal mice showed Ga:I ratios near 1 in the blood and other tissues not involved in degradation and label excretion. In tissues of the reticulo-endothelial system (RES) and the kidneys, Ga:I ratios up to 2.51 were reached within 4 days of administration. In antigen-positive MeWo tumor tissue, retention of 67Ga also excreted that of 131I, so that tumor; organ ratios (except tumor:liver) were superior for the 67Ga-labeled MAb. It is concluded that the method of coupling pre-established 67Ga-P-EDDHA chelate to antibody results in a functionally intact tracer molecule, whose persistence in vivo is not significantly impaired. The major difference to I-labeled MAbs may be a prolonged retention of Ga in tissues (cells) physiologically involved in antibody catabolism.
D000818:Animals; D000911:Antibodies, Monoclonal; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D008545:Melanoma / Q000000981:diagnostic imaging; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D007457:Iodine Radioisotopes; C011813:ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid)