Melanoma is a neoplasia of dramatically increasing incidence that has a propensity to spread rapidly. Early detection is fundamental and patient management requires reliable, sensitive and reproducible staging methods, such as a single examination by planar scintigraphy or single-photon emission tomography (SPET) using a radiopharmaceutical with selectivity for melanoma tissue. Among iodobenzamides reported to possess an affinity for melanoma, a new compound, N-(2-diethylaminoethyl)-2-iodobenzamide (BZA(2)), was selected for a clinical trial in view of its pharmacokinetic experimental profile in melanoma-bearing mice. Planar whole-body scintigraphy using (123)I-BZA(2) was performed in 25 patients with histologically proven cutaneous melanoma. Performance was evaluated in two groups of patients with one or more documented secondary lesions ( n=13) or with no known secondary lesions ( n=12), and results were compared with those of conventional investigation techniques. No adverse clinical or biological events were recorded. Lesions were imaged by increased tracer uptake, and good quality images were obtained 4 h after administration. After a follow-up of more than 1 year, the overall results of (123)I-BZA(2) scintigraphy on a per patient basis showed a sensitivity of 100%, a specificity of 95%, a positive predictive value of 86% and a negative predictive value of 100%. The proven secondary lesions were imaged with a sensitivity of 100% and a specificity of 91%. In seven patients with suspected metastases, the absence of (123)I-BZA(2) uptake was confirmed as true negative, and in one patient without suspected metastases, (123)I-BZA(2) scintigraphy revealed a gastric lesion. Hence eight diagnoses would have been modified by (123)I-BZA(2) scintigraphy data. (123)I-BZA(2) allowed discrimination between benign and malignant lesions and, in the case of malignancies, between those of melanomatous origin and others. This compound, which is selective for melanoma tissue, appears promising for the staging and restaging of melanoma.

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The cellular uptake and incorporation in macromolecules of iodine-125 labelled N-(2-diethylaminoethyl)-4-iodobenzamide ([125I]BZA), a melanoma imaging agent, was studied using human melanoma cells M3Dau (amelanotic) and M4Beu (melanotic). The interaction between [125I]BZA and synthetic melanin was examined in various conditions of incubation. The results showed that uptake was high only for M4Beu, whereas the incorporation in trichloroacetic acid-precipitable proteins was very low for both model cell lines, with no correlation with melanin content. Experiments with synthetic melanin showed that BZA binding to melanin was saturable and reversible, and involved several types of interaction. The influence of the ionic environment indicated that electrostatic forces play a role in the affinity, and the decrease in binding produced by the presence of an alcohol in the medium suggested that hydrophobic interactions may be involved in the binding mechanism. This was supported by the Scatchard analysis, which revealed two classes of binding sites, and the determination of two association constants (K1 = 3.9 +/- 1.9 x 106/M and K2 = 2.9 +/- 0.9 x 104/M). The affinity of BZA for melanin might explain the good results obtained in a phase II clinical trial for the diagnosis of malignant melanoma metastases, in which the specificity was 100%.

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