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CaNa₂EDTA for Improvement of Radioimmunodetection and Radioimmunotherapy with ¹¹¹In and ⁹⁰Y-DTPA-Anti-CEA MAbs in Nude Mice Bearing Human Colorectal Cancer

Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba
Department of Nuclear Medicine, Gunma University School of Medicine, Gunma
Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka, Japan
Department of Nuclear Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Correspondence: For correspondence or reprints contact: Naoyuki Watanabe, MD, PhD, Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

ABSTRACT

¹¹¹In and ⁹⁰Y, dissociated from ¹¹¹In-labeled-monoclonal antibody (MAb) and ⁹⁰Y-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 ¹¹¹In-MAb and ⁹⁰Y-MAb by pre- and postadministration of calcium disodium ethytenetriaminetetraacetic acid (CaNa₂EDTA). Methods: Murine MAb F33-104 against carcinoembryonic antigen (CEA) was labeled with ¹¹¹In or ⁹⁰Y by the diethylenetriamine pentaacetic (DTPA)-anhydride method. The influence of CaNa₂EDTA on loss of radioactivity from ¹¹¹In-MAb or ⁹⁰Y-MAb in serum was investigated in vitro. The effects of CaNa₂EDTA, administered before and after ¹¹¹In-MAb or ⁹⁰Y-MAb, on the biodistribution of 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% NaCI was used in both the in vitro and in vivo studies. Results: CaNa₂EDTA did not cause any decrease in levels of radioactivity of radiolabeled MAbs. Pre- and post-treatment with CaNa₂EDTA reduced radioctivity in both specific and nonspecific tumors at 72 h after ¹¹¹In-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 CaNa₂EDTA. On the other hand, CaNa₂EDTA pre- and post-treatment reduced levels of bony, hepatic, and renal radioactivity at 24, 72, and 72 h, respectively, after ⁹⁰Y-MAb injection, although it had no effect on tumor radioactivity. Conclusion: Pre-and post-treatment with CaNa₂EDTA would be of great use in humans who undergo RID or RIT with ¹¹¹In-MAb and ⁹⁰Y-MAb accompanied by disassociation of the labeled radionuclides.

Key Words: ¹¹¹In • ⁹⁰Y • calcium disodium ethylenediaminetetraacetic acid • radioimmunodetection • radioimmunotherapy

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