In Vitro and in Vivo Comparison of Binding of 99m-Tc-Iabeled Anti-CEA MAb F33-104 with 99m-Tc-labeled Anti-CEA MAb BW431/26

N. Watanabe; N. Oriuchi; S. Sugiyama; M. Kuroki; Y. Matsuoka; S. Tanada; H. Murata; T. Inoue; Y. Sasaki

doi:10.1055/s-0038-1632202

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 1999; 38(04): 115-119
DOI: 10.1055/s-0038-1632202

Originalarbeiten — Original Articles

Schattauer GmbH

In Vitro and in Vivo Comparison of Binding of 99m-Tc-Iabeled Anti-CEA MAb F33-104 with 99m-Tc-labeled Anti-CEA MAb BW431/26

Vergleich der In-vitro- und In-vivo-Bindung von 99m-Tc-markiertem Anti-CEA MAb F33-104 mit Anti-CEA MAb BW 431/26

N. Watanabe

¹Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba;

²department of Nuclear Medicine, Gunma University School of Medicine, Gunma;

,

N. Oriuchi

²department of Nuclear Medicine, Gunma University School of Medicine, Gunma;

,

S. Sugiyama

³Department of Radiology. Takasaki National Hospital, Gunma;

,

M. Kuroki

⁴Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka, Japan

,

Y. Matsuoka

⁴Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka, Japan

,

S. Tanada

¹Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba;

,

H. Murata

¹Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba;

,

T. Inoue

²department of Nuclear Medicine, Gunma University School of Medicine, Gunma;

,

Y. Sasaki

¹Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba;

› Institutsangaben

Abstract

Summary

Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tclabeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 10⁷ of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tcactivity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

Zusammenfassung

Ziel: Ziel der vorliegenden Studie war die Abschätzung der Möglichkeit eines Radioimmunnachweises (radioimmunodetection = RAID) monoklonaler, gegen das karzinoembryonale Antigen (CEA) gerichteter, mit Technetium-99m (99m-Tc) markierter Antikörper (MAK) F33-104 von Mäusen mit Hilfe einer Reduktionsmethode. Methode: Die Bindungskapazität der 99m-Tc-Anti-CEA MAK F33-104 an CEA wurde in vitro mittels Immunoradiometrie und Zellbindungstests und in vivo bei nackten Wirtmäusen mit menschlichem LS 180 Kolonadenokarzinom untersucht und dann mit 99m-Tc-Anti-CEA MAK BW 431/26 verglichen. Ergebnisse: Das Bindungsverhältnis der mit 99m-Tc-Anti-CEA markierten Antikörper F33-104 war für gelöstes, sowie für an die Zellmembran gebundenes CEA bedeutend größer als für der mit 99m-Tc-Anti-CEA markierten Antikörper BW 431/26 (34,1 ± 0,95% gegenüber 11,9 ± 0,55% in 100 ng/mL des gelösten CEA, 83,5 ± 2,84% gegenüber 54,0 ± 2,54% in 10⁷ der LS 180 Zellen). Die Akkumulation der 99m-Tc-Anti-CEA MAK F33-104 im Tumor war 18 Stunden nach der Injektion bedeutend höher als der 99m-Tc-Anti-CEA MAK BW 431/26 in der In-vivo-Studie (20,1 ± 3,50% ID/g gegenüber 14,4 ± 3,30% ID/g). Die in den Nieren der Wirtstiere mit den LS 180 Tumoren 18 Stunden nach der Injektion der 99m-Tc-Anti-CEA MAK F33-104 akkumulierte Radioaktivität des 99m-Tc war bedeutend höher als die drei Stunden nach Injektion akkumulierte (12,8 ± 2,10% ID/g gegenüber 8,01 ± 2,10% ID/g im 99m-Tc-Anti-CEA MAK F33-104, 10,7 ± 1,70% ID/g zu 8,10 ± 1,75% ID/g im 99m-Tc-Anti-CEA MAK BW 431/26). Schlußfolgerung: 99m-Tc markierte Anti-CEA MAK F33-104 sind potentielle Radiopharmazeutika für RAID bei rezidivierenden Kolorektalkarzinomen.

Key words

Radioimmunodetection - 99m-Tc-labeled anti-CEA MAb F33-104 - 99m-Tc-labeled anti-CEA MAb BW431/26 - reduction-mediated labeling method - renal uptake

Schlüsselwörter

Radioimmunnachweis - 99m-Tc-markierte Anti-CEA monoklonale Antikörper F33-104 - 99m-Tc-markierte Anti-CEA monoklonale Antikörper BW 431/26 - Reduktionsmethode - Aufnahme in den Nieren

Volltext

Referenzen

REFERENCES
1 Baum RP, Lorenz M, Hertel A, Baew-Chritow T, Schwarz A, Hör G. Successful immunoscintigraphic tumor detection with technetium-99m marked monoclonal anti-CEA antibodies. Nuklearmedizin 1989; 12 (Suppl. 01) 26-9.
2 Kuroki M, Haruno M, Murakami M. et al. Epitope mapping of the nonspecific crossreacting antigen using various related recombinant proteins expressed in Chinese hamster ovary cells and eight distinct monoclonal antibodies. Immunol Invest 1992; 21: 143-58.
3 Lind P, Lechner P, Arian-Schad K. et al. Anticarcinoembryonic antigen immuno-scintigraphy (Technetium-99m-monoclonal antibody BW431/26) and serum CEA levels in patients with suspected primary and recurrent colorectal carcinoma. J Nucl Med 1991; 32: 1319-25.
4 Mather SJ, Ellison D. Reduction-mediated technetium-99m labeling of monoclonal antibodies. J Nucl Med 1990; 31: 692-7.
5 Oriuchi N, Endo K, Watanabe N. et al. Semiquantative SPECT tumor uptake of technetium-99m-labeled anti-CEA monoclonal antibody in colorectal tumor. J Nucl Med 1995; 36: 679-83.
6 Pimm MV, Rajput RS, Frier M, Gribben SJ. Anomalies in reduction-mediated technetium-99m labelling of monoclonal antibodies. Eur J Nucl Med 1991; 18: 973-6.
7 Sakahara H, Saga T, Onodera H. et al. Antimurine antibody response to mouse monoclonal antibodies in cancer patients. Jpn J Cancer Res 1997; 88: 895-9.
8 Schwarz A, Steinstrasser A. A novel approach to Tc-99m labeled monoclonal antibody [abstract]. J Nucl Med 1986; 28: 685-93.
9 Steinsträßer A, Oberhausen E. Anti-CEA Labelling Kit BW431/26. Nuklearmedizin 1995; 34: 232-42.
10 Watanabe N, Oriuchi N, Sugiyama S, Kuroki M, Matsuoka Y. Radioimmuno-scintigraphy of colorectal cancer with technetium-99m-labeled murine anti-carcinoembryonic antigen monoclonal antibody in athymic nude mice. Ann Nucl Med 1994; 8: 23-30.
11 Zimmer AM, Kazikiewicz JM, Rosen S, Spies SM. Pharmacokinetics of Tc-99m (Sn) and I-131-labeled anti-carcinoembryonic antigen monoclonal antibody fragments in nude mice. Cancer Res 1987; 47: 1691-4.