European Journal of Nuclear Medicine Original article European multicentre study on melanoma immunoscintigraphy by means of 99mTc-labelled monoclonal antibody fragments Antonio G. Siccardi 1, Gian Luigi Buraggi 2, Pier Giorgio Natali 3, Gian Alfredo Scassellati 4, Giovanna Viale 1, Soldano Ferrone 5, and the European Multicentre Study Group' 1 Dipartimento di Biologia e Genetica, Universitb. di Milano, via G.B. Viotti 3/5, 1-20133 Milano, Italy 2 Istituto Nazionale Tumori, via Venezian 1, 1-20130 Mi]ano, Italy 3 Istituto Tumori Regina Elena, viale Regina Elena 291, 1-00161 Roma, Italy 4 Centro Ricerche-SORIN Biomedica, Strada per Crescentino, 1-13040 Saluggia, Italy s Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA 6 See Appendix Received August 16, 1989 and in revised form October 23, 1989 Abstract. A total of 493 melanoma patients were investi- gated by 20 European nuclear medicine departments by means of the same 99mTc-labelled immunoradiopharma- ceutical and the same immunoscintigraphy (ISG) proto- col. (i) No chemical or clinical toxicity was detected dur- ing or following the studies. (ii) Positive results were obtained in 287/363 (79%) patients (321 carrying known lesions and 42 carrying previously occult lesions): in 231 (80%) of them, 402/402 lesions were imaged; in the re- maining 56 ISG-positive patients, 108/204 lesions were imaged; in 76 patients 0/122 lesions were imaged. (iii) The fraction of melanoma lesions visualized by ISG was 510/728 (70.1%); 605 of these lesions were already docu- mented at the time of the study, and 123 were previously occult. (iv) A total of 218 documented melanoma lesions (30%) were not visualized by ISG in 132 patients: about 70% of the ISG-negative lesions were of small size (less than 2 cm diameter). (v) The melanoma nature of 69/123 previously occult lesions was confirmed by clinical criter- ia and/or additional investigations in follow-up studies. The results obtained in this study are similar to those obtained in the Italian Multicentre Study which had pre- viously been carried out with 258 melanoma patients. Key words." Immunoscintigraphy 99mTC - multicentre study Eur J Nucl Med (1990) 16:317-323 Offprint requests to : A.G. Siccardi Introduction 99mTc-labelled F(ab')2 fragments of the murine mono- clonal antibody (MoAb) 225.28S recognizing the human, high molecular weight, melanoma-associated antigen (HMW-MAA, expressed by more than 90% of melano- ma neoplastic lesions) (Natali 1984) have been extensive- ly used since 1983 in retrospective studies for melanoma radioimmunodetection (Buraggi et al. 1984a, b, 1985a; Mansi et al. 1984; Paganelli et al. 1986; Riva et al. 1985). Previously reported results have demonstrated fully the ability of this immunoreagent to localize melanoma metastatic foci with high specificity and sensitivity (Bur- aggi et al. 1984b, 1985b) and without any clinical side effects (Cascinelli et al. 1988). The results of prospective studies (Buraggi et al. 1986b, 1987) and of the Italian Multicentre Study (Siccardi et al. 1986) have confirmed the efficacy of the same immunoradiopharmaceutical. Moreover, the results of the Italian Multicentre Study have disclosed that although the performance of immunoscintigraphy (ISG) is influenced by a number of tumour variables such as anatomic localization, size, antigenic profile and clinical stage, the method is capable of detecting a significant number (about 24%) of clini- cally unknown lesions and, in several cases, of providing the first evidence of tumour recurrence. 99mTc-labelled 225.28S (F(ab')2 fragments have also been successfully employed in other European studies (Bockisch et al. 1989; Bfill et al. 1986; Cerny et al. 1987; Dudczak et al. 1987; Liewendahl et al. 1986; Lukac and Spaventi 1988; Rentsch etal. 1989; Scheidhauer etal. 1985) to perform ISG of primary and metastatic malig- © Springer-Verlag 1990