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, Table of Contents

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

Authors

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;

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

Full Text

References

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