Technetium-99m, rhenium-186, and rhenium-188 direct-labeled antibodies

Antibody sulfhydryl groups can act as effective carriers of reduced technetium and rhenium species for radioimmunodetection and radioimmunotherapy.

Intact immunoglobulin G and fragments were labeled with the isotopes and examined in vitro and in vivo.

Technetium bound to intact immunoglobulin G was found to be the most stable species in vitro, but in vivo, clearances of technetium and rhenium bound to intact antibody were similar. Serum clearances were faster than those seen for the corresponding radioiodinated antibodies. In vivo clearance rates of the radiolabeled fragments were similar, with kidney uptake and retention seen. Rhenium-labeled antibodies, despite a greater tendency toward in vitro reoxidation than technetium-labeled antibodies, did not show enhanced kidney clearance in animal models. Rhenium-188 and technetium-99m were obtained from similar generator systems in carrier-free form. Using rhenium-188 spiked with cold rhenium, it was determined that approximately one rhenium atom per molecule of antibody can be conjugated directly. Rhenium-186 also was coupled at almost a 1:1 ratio to antibody.

Only radiolysis concerns will limit the amount of rhenium-188 conjugated to antibody. Large doses of antibody will be necessary to deliver rhenium-186 at this isotope's currently available specific activity. Otherwise, higher specific activity rhenium-186, and/or greater loading capacity of rhenium-186 onto antibody, will be needed to generate the type of product that will be usable at a clinical dose of several hundred millicuries.