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DOI: 10.1055/s-0038-1629747
Immunszintigraphie xenotrans-plantierter Mammakarzinome
99mTc-markierte monoklonale Anti-Muzinantikörper BM-7 und 12H12Imaging Studies of Breast Cancer XenograftsMonoclonal Anti-Mucin Antibodies BM-7 and 12H12 Labeled with 99mTcPublication History
Eingegangen:
23 December 1994
in revidierter Form:
16 April 1995
Publication Date:
04 February 2018 (online)

Zusammenfassung
Gegenstand dieser Arbeit waren tierexperimentelle Untersuchungen zur Biodistribution und Immunszintigraphie der Anti-Muzin-MoAbs 12H12 und BM-7 in thymusaplastischen Nacktmäusen mit xenotransplantierten humanen Mammakarzinomen. Die MoAb waren mit 99mTc markiert; ihre Biodistribution wurde im Tiermodell 24 und 48 h nach i. v. Injektion untersucht. Die 99mTc-Markierungen der MoAbs 12H12 und BM-7 führten zu einer Tumoranreicherung von 20,7% bzw. 8,8% ID/g und zu Tumor/Muskel-Quotienten von 31 bzw. 18 nach 48 h. Im-munszintigraphisch ließ sich mit beiden MoAbs nach 24 h das Mammakarzinom AR gut darstellen. Die beiden MoAbs erfahren im Tiermodell eine schnelle Tumoraufnahme und rasche Blut-Clearance.
Summary
The present study was undertaken to evaluate the correlation of the favorable in vitro characteristics of the anti-mucin Mabs 12H12 and BM-7 with high tumor accumulation in vivo. They were labeled with 99mTc; their biodistribution in nude mice bearing mammary tumor xenograft AR was examined and immunoscintigraphy was performed after 24 h. 99mTc-labeling of the Mabs 12H12 and BM-7 led to tumor uptakes of 20.7% and 8.8% ID/g, respectively, after 48 h. Tumor-to-muscle ratios were 31 (12H12) and 18 (BM-7). Tumor xenografts were clearly visualized in immunoscintigrams. Combination of Mab 12H12 and 99mTc provides high tumor-to-tissue ratios shortly after administration.
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LITERATUR
- 1 Athanassiou A, Pectasides D, Pateniotis K. et al. Immunoscintigraphy with 131I-labeled HMFG-2 and HMFG-1 F(ab’)2 in the preoperative detection of clinical and subclinical lymph node metastases in breast cancer patients. Int J Cancer 1988; 3 Suppl 89-95.
- 2 Bastert G, Eichler A, Kaul S. Monoclonal antibodies against human breast cancer. In: Immune-deficient animals in biomedical research. Rygaard Brünner. (eds). Basel: Karger; 1987: 224-7.
- 3 Baum RP, Hertel A, Lorenz M. et al. 99mTc labeled anti-CEA monoclonal antibody for tumor immunoscintigraphy: first clinical results. Nucl Med Commun 1989; 10: 345-52.
- 4 Briimmendorf TH, Kaul S, Schuhmacher J. et al. Immunoscintigraphy of human mammary carcinoma xenografts using monoclonal antibodies 12H12 and BM-2 labeled with 99mTc and radioiodine. Cancer Res 1994; 54: 4162-8.
- 5 DeLand FH, Kim E, Corgan R. et al. Axillary lymphoscintigraphy in radioimmunodetec-tion of carcinoembryonic antigen in breast cancer. J Nucl Med 1979; 20: 1243-50.
- 6 Gendler S, Taylor-Papadimitriou J, Duhig T, Rothbard J, Burchell J. A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J Biol Chem 1988; 263: 12820-2.
- 6a Hnatovich DJ, Mardirossian G, Rusckowski M. et al. Directly and indirectly 99mTc-labeled antibodies. A comparison of in vitro and animal in vivo properties. J Nucl Med 1993; 34: 109-19.
- 7 Kairemo KJ. Immunolymphoscintigraphy with 99mTc-labeled monoclonal antibody (BW 431/26) reacting with carcinoembryonic antigen in breast cancer. Cancer Res 1990; 50 Suppl 449-54.
- 8 Kaul S, Windecker S, Bastert G. Monoclonal antibodies reactive with tumor-associated epitopes of breast mucin glycoproteins. Proc Am Assoc Cancer Res 1989; 30: 349.
- 9 Kaul S, Bastert G. Monoklonale Antikörper zur Diagnostik und Therapie bei gynäkologischen Tumoren einschließlich des Mammakarzinoms. Aktuelle Onkologie 42. München: Zuckerschwert; 1987: 42.
- 9a Kaul S, Windecker S, Bastert G. TAG12: Reinigung und Produktion von monoklonalen Zweitantikörpern. Aktuelle Onkologie 50. München: Zuckerschwert; 1989: 47-53.
- 10 Lamki LM, Buzdar AU, Singletary E. et al. Indium-Ill labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase 1 study. J Nucl Med 1991; 32: 1326-32.
- 11 Lightenberg MJL, Genissen AMC, Vos HL, Hilkens J. A single nucleotide polymorphism in an exon dictates allele-dependent differential splicing of episilian mRNA. Nucleic Acids Res 1990; 19: 297-301.
- 12 Lind P, Smola MG, Lechner P. et al. The immunoscintigraphic use of 99mTc-labeled monoclonal anti-CEA antibodies (BW 431/26) in patients with suspected primary, recurrent and metastatic breast cancer. Int J Cancer 1991; 47: 865-9.
- 13 Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA. Determination of the immuno-reactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Meth 1984; 72: 77-89.
- 14 Mardirossian G, Wu C, Rusckowski M, Hnatovich DJ. The stability of 99mTc directly labeled to an Fab’ antibody via stannous ion and mercaptoethanol reduction. Nucl Med Commun 1992; 13: 503-12.
- 15 Mattes MJ, Major PP, Goldenberg DM. et al. Pattern of antigen distribution in human carcinomas. Cancer Res 1990; 50 Suppl 880-4.
- 16 Matzku S, Bihl H. Tumor localization by immunoscintigraphy: potential and limitations. In: Molecular diagnosis of cancer. Wagener Neumann. (eds). Berlin, Heidelberg, New York: Springer; 1993: 207-17.
- 17 Merino MJ, Monteagudo C, Neumann RD. Monoclonal antibodies for radioimmuno-scintigraphy of breast cancer, Vol 18. Nucl Med Biol 1991; 4: 437-43.
- 18 Pateisky N, Schatten C, Enzelsberger H. et al. Immunlymphszintigraphie. Dtsch Med Wschr 1988; 113: 250-5.
- 19 Robbins PF, Eggensperger D, Qi C-F, Schlom J. Definition of the expression of the human carcinoembryonic antigen and nonspecific cross-reacting antigen in human breast and lung carcinomas. Int J Cancer 1993; 53: 892-7.
- 20 Salgado L, Vieira MR, Baum RP. et al. Clinical value of immunoscintigraphy in breast cancer patients with a new antibody (12H12) labeled with 99mTc. Book of abstracts, 5th annual meeting on diagnostic and therapeutic applications of radiolabeled antibodies and receptors for diagnostic and therapeutic purposes, Ft. Lauderdale, Jan. 14th—17th, 1993
- 21 Schlom J. Basic principles and application of monoclonal antibodies in the management of carcinomas. Cancer Res 1986; 46: 3225-38.
- 22 Schuhmacher J, Klivényi G, Matys R. et al. Multistep tumor targeting in nude mice using bispecific antibodies and a gallium chelate suitable for immunoscintigraphy with positron emission tomography. Cancer Res 1995; 55: 115-23.
- 23 Schwarz A, Steinsträsser A. A novel approach to 99mTc labeled monoclonal antibodies (abstract). J Nucl Med 1987; 28: 721.
- 24 Strous GJ, Dekker J. Mucin-type glycoproteins. Critic Rev Biochem Mol Biol 1992; 27: 57-92.
- 25 Swallow DM, Gendler S, Griffith B. et al. The human tumor-associated epithelial mucins are coded by an expressed hypervariable gene locus PUM. Nature 1987; 328: 82.
- 26 Sykes TR, Woo TK, Qi P, Baum RP, Noujaim AA. Direct labeling with 99mTc by a novel photoactivation process. J Nucl Med 1993; 35 Suppl 100.
- 27 Taylor-Papadimitriou J, Peterson JA, Arklie J. et al. Monoclonal antibodies to epithelial-specific components of the human milk fat globule membrane. Production and reaction with cells in the culture. Int J Cancer 1981; 2: 17-28.
- 28 Windecker S, Khazaeli MB, LoBulgio AF, Shaw DR, Kaul S. Circulating level of TAG-12 breast carcinoma-associated antigen. Proc Am Assoc Cancer Res 1990; 31: 262.
- 29 Zotter S, Hageman PC, Lossnitzer A, Mooi WJ, Hilgers J. Tissue and tumor distribution of human polymorphic epithelial mucin. Cancer Rev 1988; 11: 55-101.