CaNa(2)EDTA for improvement of radioimmunodetection and radioimmunotherapy with In-111 and Y-90-DTPA-anti-CEA MAbs in nude mice bearing human colorectal cancer

In-111 and Y-90, dissociated from In-111-labeled-monoclonal antibody (MAb) and Y-90-labeled MAb, may cause deterioration of the image quality in radioimmunodetection (RID) and undesirable irradiation of nontargeted tissue in radioimmunotherapy (RIT), respectively. The aim of this study was to investigate any improvement in RID and RIT with (111)ln-MAb and Y-90-MAb by pre- and postadministration of calcium disodium ethylenetriaminetetraacetic acid (CaNa(2)EDTA). Methods: Murine MAb F33-104 against carcinoembryonic antigen (CEA) was labeled with In-111 or Y-90 by the diethylenetriamine pentaacetic (DTPA)-anhydride method. The influence of CaNa(2)EDTA on loss of radioactivity from In-111-MAb or Y-90-MAb in serum was investigated in vitro. The effects of CaNa(2)EDTA, administered before and after In-111-MAb or Y-90-MAb, on the biodistribution or radioactive isotopes in nude mice bearing human colon adenocarcinoma LS 180 tumor expressing CEA, or human pulmonary carcinoma PC 9 tumor expressing no CEA, were then examined. As a control, 0.9% NaCl was used in both the in vitro and in vivo studies. Results: CaNa(2)EDTA did not cause any decrease in levels of radioactivity of radiolabeled MAbs. Pre- and post-treatment with CaNa(2)EDTA reduced radioctivity in both specific and nonspecific tumors at 72 h after In-111-MAb injection resulting in an increase of the specific tumor-to-nonspecific tumor radioactivity ratio. The levels of hepatic and renal radioactivity were also subsequently decreased by CaNa(2)EDTA. On the other hand, CaNa(2)EDTA pre- and post-treatment reduced levels of bony, hepatic, and renal radioactivity at 24, 72, and 72 h, respectively, after Y-90-MAb injection, although it had no effect on tumor radioactivity, Conclusion: Pre- and post-treatment with CaNa(2)EDTA would be of great use in humans who undergo RID or RIT with In-111-MAb and Y-90-MAb accompanied by disassociation of the labeled radionuclides.