LACK OF EXPRESSION OF DOPAMINE D2 RECEPTORS IN MALIGNANT-MELANOMA - EVIDENCE FOR INTERACTION OF IODOBENZOFURANS WITH MELANIN

Objectives: (1) To compare scintigraphy using the new dopamine D2 rece ptor binding radioligand iodobenzofuran (IBF) versus whole-body positr on emission tomography (PET) in demonstrating metastasizing melanoma, and (2) to determine, for the first time using a panel of histochemica l techniques, whether the ability of D2 receptor binding radioligands to detect melanoma metastases is due to tumor-expressed D2 receptors, Methods: Seven patients with metastatic melanoma were examined using I -123-IBF scintigraphy, Findings were compared to the results of PET an d metastasis histochemistry: D2 receptor mRNA assay (metastases: n = 5 ; melanoma cell lines: n = 4) using the reverse transcriptase polymera se chain reaction (RT-PCR) versus D2 receptor-transfected Chinese hams ter ovary cell controls: in vitro I-125-IBF binding (n = 19), and immu nohistochemical staining for dopamine D2 receptor protein (n = 19), Re sults: IBF scintigraphy detected 2/10 melanoma metastases detected by PET (sensitivity 20%). No dopamine D2 receptor mRNA was found in melan oma cells using RT-PCR. The binding of I-125-IBF correlated with the a mount of melanin present in the metastases; two amelanotic melanomas b oth failed to bind I-125-IBF. Immunohistochemical staining was negativ e in all metastases, Conclusion: Melanoma cells do not appear to expre ss dopamine D2 receptors, Although IBF had high dopamine D2 receptor a ffinity, its ability to detect melanoma metastases is more likely expl ained by low affinity binding to melanin than by the presence of dopam ine receptors.