High-contrast PET of melanoma using (18)F-MEL050, a selective probe for melanin with predominantly renal clearance.
The aim of this study was to evaluate the novel probe (18)F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ((18)F-MEL050) for the imaging of primary and metastatic melanoma.


METHODS
PET using (18)F-MEL050 was performed in murine models of melanoma. The specificity of (18)F-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. (18)F-MEL050 PET results were compared with (18)F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of (18)F-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs.


RESULTS
In pigmented B16-F0 grafts, (18)F-MEL050 PET yielded a tumor-to-background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for (18)F-MEL050 than for (18)F-FDG (50.9 +/- 6.9 vs. 5.8 +/- 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of (18)F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor-bearing mice on PET at 2 h after tracer injection, with high concordance between (18)F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy.


CONCLUSIONS
(18)F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.
Centre for Molecular Imaging and Translational Research Laboratory, Peter MacCallum Cancer Centre, Victoria, Australia.
Delphine
D
Denoyer
Ivan
I
Greguric
Peter
P
Roselt
Oliver C
OC
Neels
Nicolas
N
Aide
Stephen R
SR
Taylor
Andrew
A
Katsifis
Donna S
DS
Dorow
Rodney J
RJ
Hicks
D000818:Animals; D001345:Autoradiography; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D014057:Tomography, X-Ray Computed; D014184:Transplantation, Homologous; D051598:Whole Body Imaging
D003287:Contrast Media; D005462:Fluorine Radioisotopes; D008543:Melanins; C543821:N-(2-(diethylamino)ethyl)-6-fluoronicotinamide; D011725:Pyridines; D019788:Fluorodeoxyglucose F18; D009536:Niacinamide