Nuklearmedizin 1986; 25(06): 216-219
DOI: 10.1055/s-0038-1624345
Originalarbeiten — Original Articles
Schattauer GmbH

Enhancement of Tumor Contrast on Radioimmunoscans by Using Mixtures of Monoclonal Antibody F(ab’)2 Fragments[*] [*]

D. L. Munz
1   From the Wistar Institute of Anatomy and Biology and the Hospital of the University of Pennsylvania, Department of Radiology, Division of Nuclear Medicine, Philadelphia, PA, USA
,
A. Alavi
1   From the Wistar Institute of Anatomy and Biology and the Hospital of the University of Pennsylvania, Department of Radiology, Division of Nuclear Medicine, Philadelphia, PA, USA
,
H. Koprowski
1   From the Wistar Institute of Anatomy and Biology and the Hospital of the University of Pennsylvania, Department of Radiology, Division of Nuclear Medicine, Philadelphia, PA, USA
,
D. Herlyn
1   From the Wistar Institute of Anatomy and Biology and the Hospital of the University of Pennsylvania, Department of Radiology, Division of Nuclear Medicine, Philadelphia, PA, USA
› Author Affiliations
Further Information

Publication History

Received: 28 August 1986

Publication Date:
20 January 2018 (online)

F(ab’)2 fragments of MAbs GA 73-3 (IgG 2a) and CO 29.11 (IgG 1), which detect distinct antigenic determinants on adenocarcinoma cells of the gastrointestinal tract, were labeled with 131I using the iodogen method. 41 nude mice bearing SW-948 CRC tumors were injected either with a mixture of 100 ¼Ci (11 ¼g) each (n = 9) of the two 131l-F(ab’)2 fragments or with either fragment alone at various doses (each group consisting of 8 mice): GA 73-3,100 ¼Ci (11 ¼g) and 200 ¼Ci (25 ¼g); CO 29.11,100 ¼Ci (11 ¼g) and 200 ¼Ci (26 ¼g). Whole-body images of the mice were obtained daily for up to six days after injection. Ratios of cpm/pixel in the tumor to those in the rest of the body (rob), representing tumor contrast, were significantly (p <0.05) higher in the group of mice injected with the mixture (3.9 ± 1.5) as compared to those given 100 or 200 jiCi of either fragment separately. The biological half-life (T1/2 biol) of the mixture (44.7 ± 14.5 h) in the CRC tumors was significantly (p <0.05) longer than T1/2 biol determined in the groups given either fragment alone. Tv bioL in the rob was similar in all groups of mice examined.

Zusammenfassung

F(ab’)2-Fragmente der monoklonalen Antikörper (MAbs) GA 73-3 (IgG 2a) und CO 29.11 (IgG 1), welche verschiedene, gut charakterisierte Antigendeterminanten auf Adenokarzinomzellen des Gastrointestinaltraktes erkennen, wurden mit Hilfe der Iodogen-Methode mit 131 J markiert. 41 kolorektale Karzinome (CRC) menschlichen Ursprungs tragenden Nacktmäusen wurde entweder eine Mischung von jeweils 100 ¼Ci bzw. 11 ¼g (n = 9) der beiden 131J-markierten F(ab’)2-Fragmente oder jedes markierte Fragment separat in verschiedener Dosierung verabfolgt (jede Gruppe bestand aus 8 Mäusen): G A 73-3: 100 ¼Ci (11 ¼g) und 200 ¼Ci (25 ¼g); CO 29.11: 100 ¼Ci (11 ¼g) und 200 [id (26 ¼g). Ganzkörperszintigramme der Tiere wurden bis zu sechs Tagen nach Injektion angefertigt. Die Verhältnisse der cpm/pixel in den Tumoren zu denjenigen im Restkörper (rob), welche den Tumorkontrast wiedergeben, waren in der Gruppe mit dem Antikörper-Fragment-Gemisch (3,9 ± 1,5) signifikant (p <0,05) höher als in jenen Gruppen von Mäusen, die lediglich jeweils eine Komponente in verschiedener Dosierung erhalten hatten. Die biologische Halbwertszeit (T1/2 biol) des MAb-Fragment- Gemisches in den CRC-Tumoren (44,7 ± 14,5 h) war signifikant (p <0,05) länger als die in den Gruppen mit nur jeweils einem applizierten Fragment ermittelte. T1/2 biol. im r°b der Mäuse war in allen untersuchten Gruppen ähnlich.

* Presented at the Symposion on “Monoclonal Antibodies in Nuclear Medicine” in Freiburg i.Br., May 1-3, 1986.


** Supported by the Deutsche Forschungsgemeinschaft , Heisenberg-Programm (Mu 693/1-1).


 
  • REFERENCES

  • 1 Ernst C. S, Shen J-W, Litwin S. et al. Multiparameter evaluation of the expression in situ of normal and tumor-associated antigens in human colorectal carcinoma. Int. J. Cancer. 1986 37. (in press).
  • 2 Herlyn M, Blaszczyk M, Bennicelli J. et al. Selection of monoclonal antibodies detecting sérodiagnostic human tumor markers. J. immunol. Meth 1985; 80: 107-16.
  • 3 Herlyn D, Herlyn M, Ross A. H. et al. Efficient selection of human tumor growth- inhibiting monoclonal antibodies. J. immunol. Meth 1984; 73: 157-67.
  • 4 Herlyn D, Powe J, Alavi A. et al. Radioimmunodetection of human tumor xenografts by monoclonal antibodies. Cancer Res 1983; 43: 2731-5.
  • 5 Herlyn D, Powe J, Munz D. L. et al. Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab’)2 fragments. Int. J. nucl. Med. Biol 1986; 13: 401-5.
  • 6 Herlyn M, Steplewski Z, Herlyn D, Koprowski H. Colorectal carcinoma specific antigen: Detection by means of monoclonal antibodies. Proc. natl. Acad. Sei 1979; 76: 1438-42.
  • 7 Munz D. L, Alavi A, Koprowski H, Herlyn D. Improved radioimmunoimaging of human tumor xenografts by a mixture of monoclonal antibody F(ab’)2 fragments. J. nucl. Med 1986; 27: 1739-45.
  • 8 Steplewski Z, Herlyn M, Herlyn D, Clark w. H, Koprowski H. Reactivity of monoclonal anti-melanoma antibodies with melanoma cells freshly isolated from primary and metastatic melanomas. Eur. J. Immunol 1979; 09: 94-6.
  • 9 Wahl R. L, Parker C. W, Philpott G. W. Improved radioimmunoimaging and tumor localization with monoclonal F(ab’)2 . J. nucl. Med 1983; 24: 316-25.