Preliminary Study of Radionuclide-Labeled MerTK-Targeting PET Imaging Agents for the Diagnosis of Melanoma

J Med Chem. 2024 Nov 14;67(21):19813-19825. doi: 10.1021/acs.jmedchem.4c02156. Epub 2024 Nov 1.

Abstract

MerTK PET imaging holds potential as a promising approach for assessing tumor aggressiveness and monitoring treatment response. In this study, we synthesized a series of 18F- and 68Ga-labeled tracers derived from MerTK inhibitors for detection of MerTK expression. Among the synthesized agents, the dimeric compounds [68Ga]10 and [68Ga]12 demonstrated good in vivo and in vitro stability, high affinities to the MerTK receptor, and good MerTK-targeting specificity. Notably, [68Ga]10 exhibited a tumor uptake of 2.6 ± 0.2%ID/g at 1 h p. i. in B16F10 tumor-bearing mice, nearly tripling the uptake of its monomeric counterpart [68Ga]3. A similar enhancement was observed with [68Ga]12 compared to its monomeric analog [68Ga]6. Additionally, [18F]14 achieved a tumor uptake of 7.6 ± 0.5%ID/g at 2 h p. i., outperforming the previously reported [18F]15. Biodistribution analysis further validated the results, highlighting their potential for clinical investigation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Fluorine Radioisotopes* / chemistry
  • Gallium Radioisotopes* / chemistry
  • Humans
  • Melanoma, Experimental / diagnostic imaging
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / pharmacokinetics
  • Tissue Distribution
  • c-Mer Tyrosine Kinase* / metabolism

Substances

  • c-Mer Tyrosine Kinase
  • Radiopharmaceuticals
  • Gallium Radioisotopes
  • Fluorine Radioisotopes
  • Fluorine-18
  • Gallium-68