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.
Denoyer
Delphine
D
Centre for Molecular Imaging and Translational Research Laboratory, Peter MacCallum Cancer Centre, Victoria, Australia.
Greguric
Ivan
I
Roselt
Peter
P
Neels
Oliver C
OC
Aide
Nicolas
N
Taylor
Stephen R
SR
Katsifis
Andrew
A
Dorow
Donna S
DS
Hicks
Rodney J
RJ
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