Technetium-99m-labeled monoclonal antibodies: Influence of technetium-99m binding sites

A number of ^99mTc-labeled monoclonal antibodies (Mabs) are being evaluated for diagnostic applications. Preparations are carried out using both direct and indirect (bifunctional chelating agent, BFCA) labeling procedures in which nonspecific ^99mTc binding has been postulated. Methods: By using the ascorbic acid (AA) reduction mediated direct labeling procedure and diaminotetrathiol (N₂S₄) as a BFCA method, we examined the role of specific binding sites and aliphatic E amino groups of lysine as nonspecific binding sites for ^99mTc. Results: Labeling yields for the direct and N₂S₄ 'regular' preparations averaged 73% ± 2.8% and 91% ± 2%, for the 'specific' preparations, 60% ± 3.5% and 75% ± 2% and for the 'nonspecific' preparations 13% ± 1.0% and 16% ± 1% respectively. All preparations were evaluated in tumor-bearing mice. The control and specific preparations permitted excellent scintigraphic visualization of tumors; the percentages of specific preparations in the tumors being 2.1% ± 0.5% and 3.1% ± 0.4%, respectively. With nonspecific preparations, tumors were not visualized and the percentages of administered radioactivity per gram of tumor were only 0.9% ± 0.2% and 0.9% ± 0.3%, respectively. Conclusions: In these ^99mTc labeling procedures, the amino group-mediated nonspecific binding of ^99mTc to Mabs can be as high as 16% and contributes to increased liver uptake and decreased tumor uptake of radioactivity.