Coupling of the 99mtechnetium-nitrido group to monoclonal antibody and use of the complexes for the detection of tumors in mice.
The in vivo detection of tumors by immunoscintigraphy with the use of radiolabeled monoclonal antibodies (MoAb) is a new diagnostic procedure currently undergoing clinical evaluation. In the present study the use of 99mtechnetium (99mTc) for this purpose was explored. A simple method for the labeling of microgram quantities of MoAb with 99mTc based on the substitution reaction of MoAb and tetrachloronitridotechnetate ion (99mTcNCl4-) is described. The selective activity of the 99mtechnetium-nitrido-MoAb (99mTcN-MoAb) complexes was proved in vitro by a binding assay with different target cells. The 99mTcN-MoAb complexes were shown to bind reactive cells up to 20 times more avidly than nonreactive cells. The specificity of the 99mTcN-MoAb complexes was shown in vivo. (C57BL/6 X BALB/c)F1 mice bearing palpable tumors (0.3-1.5 cm in diameter) were given an iv injection of 1 of 2 MoAb (one reactive and the other nonreactive) identically labeled with 99mTcNCl4- and then scanned with a gamma camera, and/or the tissues were removed and the localization of 99mTc-nitrido group-labeled MoAb was measured. Tumor localization of the reactive MoAb (1.8-2.2% of the injected dose) was four times greater than that of the nonreactive 99mTcN-MoAb (0.3-0.4% of the injected dose). The localization of specific 99mTcN-MoAb to a murine thymoma was observed in the gamma camera image at just 2 hours after injection. At 27 hours, tumors could readily be detected by 99mTcN-MoAb without the need for background subtraction. Nonreactive 99mTcN-MoAb did not image the tumors. The use of 99mTcN-MoAb offers substantial improvement over radioiodinated (125I or 131I) MoAb for the detection of tumors. The use of 99mTcNCl4- as a labeling agent results in 99mTc-labeled MoAb with high specific activity and specificity when compared with the specific activity and specificity of the 99mTc-MoAb prepared by using the conventional SnCl2 reduction of pertechnetate.
Kanellos
J
J
Pietersz
G A
GA
McKenzie
I F
IF
Bonnyman
J
J
Baldas
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging; D013667:Technetium; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D013667:Technetium