N-(2-diethylaminoethyl)-2-iodobenzamide (BZA(2)) has been singled out as the most efficacious
melanoma scintigraphy imaging agent. Our work was designed to assess the mechanisms of the specific affinity of the radioiodinated iodobenzamide for
melanoma tissue. We studied the cellular uptake and retention of [(125)
I]-BZA(2) on various cell lines. In vitro, cellular [(125)
I]-BZA(2) uptake was related to the pigmentation status of the cells: higher in pigmented
melanoma cell lines (M4 Beu, IPC 227, B 16) than in a nonpigmented one (M3 Dau) and nonmelanoma cell lines (MCF 7 and L 929). Two mechanisms were assessed: binding of the tracer to
melanin or to
sigma receptors of
melanoma cells. First, the uptake of [(125)
I]-BZA(2) after melanogenesis stimulation by
alpha-melanocyte-stimulating hormone and
l-tyrosine increased in the B 16
melanoma cell line both in vitro and in vivo according to
melanin concentration. Moreover, the binding of [(125)
I]-BZA(2) to synthetic
melanin was dependent on
melanin concentration and could be saturated. Second, no competition was evidenced on M4 Beu cells between [(125)
I]-BZA(2) and
haloperidol, a sigma
ligand, at concentrations < or =10(-6) M. We show that the specificity and sensibility of BZA(2) as a
melanoma scintigraphic imaging agent are mostly due to interactions with melanic pigments.