Radioimmunodetection of Malignant Melanoma with the 225.28S Monoclonal Antibody to HMW-MAA^[*]

A review of the studies on the use of the antigen-antibody system HMW-MAA 225.28S in melanoma radioimmunodetection is reported. The results obtained in a pilot study (42 patients with 74 lesions), a multicenter trial (254 patients with 553 lesions) and a prospective study still outstanding (29 patients with 38 lesions) allow to consider this system as suitable for clinical application. F(ab′)₂ labelled with ^99mTc gave the best results in terms of positivity. Moreover this radioisotope allows the best dosimetric conditions. The gamma energy emitted by this radionuclide is particularly convenient for conventional scintillation cameras and ECT. Very good results in terms of sensitivity (70%-85%) and especially specificity (about 100%) were achieved. Possible clinical applications of the method are discussed.

Zusammenfassung

Ein Überblick über Studien zur Anwendung des Antigen-Antikörper- Systems HMW-MAA 225.28S zum Radioimmunnachweis des Melanoms wird gegeben. Die Ergebnisse, die in einer Pilotstudie (42 Patienten mit 74 Läsionen), einer Multicenterstudie (254 Patienten mit 553 Läsionen) und einer noch ausstehenden prospektiven Studie (29 Patienten mit 38 Läsionen) erhalten wurden, erlauben es, dieses System als geeignet für die klinische Anwendung anzusehen. F(ab′)₂, markiert mit ^99mTc, lieferte die besten Resultate im Hinblick auf den Positivnachweis. Darüber hinaus läßt dieses Radioisotop die besten dosimetrischen Bedingungen zu. Die von diesem Radionuklid emittierte Gamma-energie ist für konventionelle Gammakameras und ECT besonders gut geeignet. Sehr gute Resultate wurden im Hinblick auf die Sensitivität (70-85%) und besonders auf die Spezifität (gegen 100%) erhalten. Die möglichen klinischen Anwendungen dieser Methode werden diskutiert.

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

• REFERENCES

• 1 Brown J. P, Hewicj R. M, Hellström I. et al.: Human melanoma associated-antigen P97 is structurally and functionally related to transferrin. Nature 1982; 296: 171-3.
• 2 Brown J. P, Woodbury R. G, Hart C. E. et al.: Quantitative analysis of melanoma-associated antigen P97 in normal and neoplastic tissues. Proc. natl. Acad. Sei. USA 1981; 78: 539-43.
• 3 Buraggi G. L. Radioimmunodetection of cancer. J. nucl. Med 1985; 29: 261-7.
• 4 Buraggi G. L, Callegaro L, Cascinelli N. et al.: Radioimmunodetection of malignant melanoma with radiolabeled (¹³¹I, ¹²³I, ¹¹¹In, ^99mTc) monoclonal antibodies and F(ab’)2 fragments. In: Nuclear Medicine in Clinical Oncology. Winkler C. ed. Springer, Berlin – Heidelberg: 1986
• 5 Buraggi G. L, Callegaro L, Ferrone S. et al.: In vivo immunodiagnosis with radiolabeled anti-melanoma antibodies and F(ab’)2 fragments. In: Nuclear medicine: Proc., 21. Ann. Meet., SNME, Ulm 13-16 Sept. 1983: 713-6 Schattauer, Stuttgart: 1984
• 6 Buragi G. L, Callegaro L, Mariani G. et al.: Imaging with ¹³¹I-labelled monoclonal antibodies to a high-molecular-weight melanoma-associated antigen in patients with melanoma: Efficacy of whole immunoglobulin and its F(ab’)2 fragments. Cancer Res 1985; 45: 3378-87.
• 7 Buragi G. L, Callegaro L, Turrin A. et al.: Immunoscintigraphy with ¹²³I, ^99mTc and ¹¹¹In-labelled F(ab’)2 fragments of monoclonal antibodies to a human high molecular weight-melanoma associated antigen. J. nucl. Med 1984; 28: 283-95.
• 8 Buragi G. L, Turrin A, Cascinelli N. et al.: Radioimmunodetection of melanoma: Preliminary results of a prospective study. Int. J. biol. Markers 1986; 01: 47-54.
• 9 Buraggi G. L, Turrin A, Cascinelli N. et al.: Immunoscintigraphy with anti-melanoma monoclonal antibodies. In: Tumor Immunoscintigraphy. Britton K. E, Donato L. eds. Gordon and Breach, London – New York: 1986
• 10 Callegaro L, Ferrone S, Plassio G. et al.: Biochemical characterization of monoclonal antibodies and F(ab’)2 fragments against human melanoma associated antigen labelled with different radioactive isotopes. J. nucl. Med 1983; 27: 82-5.
• 11 Ferrone S, Buraggi G. L, Temponi M. et al.: Human high molecular weight melanoma associated antigen. Immunochemical profile and clinical applications. Ann. N. Y. Acad. Sei. (In press).
• 12 Ferrone S, Giacomini P, Natali P. G. et al.: A human high molecular weight-melanoma associated antigen (HMWMAA) defined by monoclonal antibodies. First Int. Meet, on Boron Neutron Capture, MIT, Boston. 12-14 October 1983: 174-83.
• 13 Giacomini P, Natali P. G, Ferrone S. Analysis of the interaction between a human high molecular weight-melanoma associated antigen and monoclonal antibodies to three distinct antigenic determinants. J. Immunol 1985; 135: 696-702.
• 14 Giacomini P, Veglia F, Fel PCordiall. et al.: Level of membrane-bound high molecular- weight melanoma-associated antigen and a cytoplasmic melanoma-associated antigen in surgically removed tissues and in sera from patients with melanoma. Cancer Res 1984; 44: 1281-87.
• 15 Hellström K. E, Hellström I, Brown J. P. Human tumor-associated antigens identified by monoclonal antibodies. Springer Sem. Immunopathol 1982; 05: 127-46.
• 16 Hellström K. E, Hellström I, Brown J. P. Monoclonal antibodies to melanoma- associated antigens. In: Monoclonal Antibodies and Cancer. Wright G. L. ed. 31-47 Marcel Dekker, New York: 1984
• 17 Imai K, Natali P. G, Kay N. E. et al.: Tissue distribution and molecular profile of a differentiation antigen detected by a monoclonal antibody (345.134S) produced against human melanoma cells. Cancer Immunol. Immunother 1982; 12: 159-66.
• 18 Imai K, Wilson B, Bigotti A. et al.: A 94,000 dalton glycoprotein expressed by human melanoma and carcinoma cells. J. natl. Cancer Inst 1982; 68: 761-69.
• 19 Larson S. M, Brown J. P, Wright P. W. et al.: Imaging of melanoma with ¹³¹Ilabeled monoclonal antibodies. J. nucl. Med 1983; 24: 123-9.
• 20 Larson S. M, Carrasquillo J. A, Krohn K. A. et al.: Localization of ¹³¹I labeled p97 specific Fab fragments in human melanoma as a basis for radiotherapy. J. clin. Invest 1983; 72: 2101-14.
• 21 Natali P. G, Cavaliere R, Matsui M. et al.: Human melanoma associated antigens identified with monoclonal antibodies: Characterization and potential clinical application. In: Cutaneous Melanoma and Precursor Lesions. Ruiter D. J, Welraart K, Ferrone S. eds. M Nijhoff, Boston: 1984
• 22 Natali P. G, Wilson B. S, Imai K. et al.: Tissue distribution, molecular profile and shedding of a cytoplasmic antigen identified by the monoclonal antibody 465.12S to human melanoma cells. Cancer Res 1982; 42: 583-9.
• 23 Reisfeld R. A, Ferrone S. Melanoma Antigens and Antibodies. Plenum Press; New York & London: 1981
• 24 Siccardi A. G, Buraggi G. L, Callegaro L. et al.: Immunoscintigraphy of human melanoma, a multicenter study of the Italian National Research Council. Cancer Res 1986; 46: 4817-22.