Recent Developments in the Radiolabeling of Antibodies with Iodine, Indium, and Technetium

The use of radiolabeled antibodies for tumor detection and therapy has provided some striking successes despite unfavorable tumor-to-normal tissue radioactivity ratios due, in part, to the accumulation of the label in normal tissues. One approach, which has been and is still under consideration to reduce unwanted background levels, is the improvement of ways in which radiolabels are attached to antibody, especially with the goal of increasing in vivo stability. Although these improvements have occurred throughout the history of this field, important developments have recently been reported in the labeling of antibodies with three radiolabels, namely radioiodine, 111In, and 99mTc. Thus, antibodies may now be labeled with radioisotopes of iodine in ways that minimize the extent of in vivo dehalogenation leading to thyroid, stomach, and gut radioactivity uptake. Newer and stronger chelates for 111In have been developed in the hope that their use would result in lower radioactivity levels in the liver. Finally, newer methods, both direct and indirect, for the attachment of 99mTc to antibodies have been developed and are now being clinically tested. Although these developments have taken place only recently and the in vivo behavior of labels attached in these ways have not yet been fully characterized, it is possible to make tentative conclusions regarding their impact. Thus, the use of stably radioiodinated antibodies appears to have resulted in modest improvements in patient images. In contrast, the use of stable chelates for labeling antibodies with 111In may have had no appreciable effect on liver radioactivity levels. The use of antibodies radiolabeled with 99mTc, especially via the newer direct labeling methods, are providing superior images in patients with low radioactivity levels in organs such as liver. However, it must still be established whether the short physical half-life of 99mTc lowers sensitivities and specificities of detection relative to other labels.