Fab fragments of
monoclonal antibodies (MoAb) to
melanoma, radiolabeled with 131I, were evaluated as diagnostic
reagents to determine their ability to localize systemic--MoAb injected intravenously (IV)--or nodal metastatic disease--injected subcutaneously (SQ) at a site proximal to draining lymph nodes. Sixty-one scans were performed (40 IV, 21 SQ) in 59 patients who had
injections of 0.2-50 mg of 131I coupled (0.2-12 mCi) antibody. These included 48.7, which identifies a high molecular weight
antigen (HMW), or 96.5, which identifies a
transferrin like molecule, p97. 125I coupled nonspecific Fab 1.4, reacting with murine leukemia virus, or the whole antibody BL3, reactive with a human B cell idiotypic determinant, was generally used in tandem with the patients injected SQ as a nonspecific control. All patients had immunohistochemical studies performed on biopsied lesions and demonstrated binding to the
antibodies injected. Of the IV patients, 22/38 (58%) had (+) scans, 13 at SQ or nodal sites, four at visceral sites, and five at visceral and SQ sites. Patients with clinical stage II disease had SQ injection of MoAb, including 11 additional patients injected with the whole antibody 9.2.27 (anti-HMW) labeled with 111In (6 patients) or 131I (5 patients). Nodal dissection was performed 2-4 days later. All 111In coupled
antibodies demonstrated excellent nodal delineation without specific identification of
tumor deposits. Of the 21 patients injected SQ with MoAb, 17 had confirmed
tumor in nodes. Of patients injected with
Fab fragments, 4/8 (50%) had specific uptake of MoAb, although only two were successfully imaged. Increased uptake of antimelanoma
antibodies was observed in some patients in lymph nodes not containing
tumor and was possibly related to
antigen shedding. Clearance of labeled antibody from the injection site occurred with a half life of 16-50 hours. Toxicity was limited to local discomfort at the site of SQ injection.
Melanoma metastases can be identified with IV or SQ injection or radiolabeled
antibodies. These
reagents may be useful in the diagnosis or
therapy of human
melanoma. Further evaluation will be required before they could be considered clinically useful.