High-contrast PET of melanoma using (18)F-MEL050, a selective probe for melanin with predominantly renal clearance

J Nucl Med. 2010 Mar;51(3):441-7. doi: 10.2967/jnumed.109.070060. Epub 2010 Feb 11.

Abstract

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.

Conclusion: (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Contrast Media / chemistry
  • Contrast Media / metabolism
  • Female
  • Fluorine Radioisotopes / chemistry*
  • Fluorodeoxyglucose F18
  • Humans
  • Kidney / metabolism*
  • Melanins / metabolism*
  • Melanoma / diagnostic imaging*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mice
  • Neoplasm Metastasis
  • Niacinamide / analogs & derivatives*
  • Niacinamide / chemistry
  • Niacinamide / metabolism
  • Positron-Emission Tomography*
  • Pyridines / chemistry
  • Pyridines / metabolism*
  • Substrate Specificity
  • Tomography, X-Ray Computed
  • Transplantation, Homologous
  • Whole Body Imaging

Substances

  • Contrast Media
  • Fluorine Radioisotopes
  • Melanins
  • N-(2-(diethylamino)ethyl)-6-fluoronicotinamide
  • Pyridines
  • Fluorodeoxyglucose F18
  • Niacinamide