Lack of expression of dopamine D2 receptors in malignant melanoma: evidence for interaction of iodobenzofurans with melanin.
OBJECTIVE
(1) To compare scintigraphy using the new dopamine D2 receptor binding radioligand iodobenzofuran (IBF) versus whole-body positron emission tomography (PET) in demonstrating metastasizing melanoma, and (2) to determine, for the first time using a panel of histochemical 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 123I-IBF scintigraphy. Findings were compared to the results of PET and metastasis histochemistry: D2 receptor mRNA assay (metastases: n = 5; melanoma cell lines: n = 4) using the reverse transcriptase polymerase chain reaction (RT-PCR) versus D2 receptor-transfected Chinese hamster ovary cell controls: in vitro 125I-IBF binding (n = 19), and immunohistochemical staining for dopamine D2 receptor protein (n = 19).


RESULTS
IBF scintigraphy detected 2/10 melanoma metastases detected by PET (sensitivity 20%). No dopamine D2 receptor mRNA was found in melanoma cells using RT-PCR. The binding of 125I-IBF correlated with the amount of melanin present in the metastases; two amelanotic melanomas both failed to bind 125I-IBF. Immunohistochemical staining was negative in all metastases.


CONCLUSIONS
Melanoma cells do not appear to express dopamine D2 receptors. Although IBF had high dopamine D2 receptor affinity, its ability to detect melanoma metastases is more likely explained by low affinity binding to melanin than by the presence of dopamine receptors.
Böni
R
R
Department of Dermatology, University Hospital of Zürich, Switzerland.
Steinert
H
H
Böni
R A
RA
Lichtensteiger
W
W
Dummer
R
R
Hartman
D S
DS
von Schulthess
G K
GK
Burg
G
G
Westera
G
G
D000328:Adult; D000368:Aged; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000556:secondary; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D007457:Iodine Radioisotopes; D008543:Melanins; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine