68Ga-DOTA-GGNle-CycMSHhex targets the melanocortin-1 receptor for melanoma imaging

  • Sci Transl Med. 2018 Nov 7;10(466):eaau4445. doi: 10.1126/scitranslmed.aau4445.
Jianquan Yang  1 ,  Jingli Xu  1 ,  Rene Gonzalez  2 ,  Thomas Lindner  3 ,  Clemens Kratochwil  4 ,  Yubin Miao  5
Affiliations
  • 1. Department of Radiology, University of Colorado Denver, Aurora, CO 80045, USA.
  • 2. Department of Medical Oncology, University of Colorado Denver, Aurora, CO 80045, USA.
  • 3. Department of Nuclear Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • 4. Department of Nuclear Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany. [email protected] [email protected].
  • 5. Department of Radiology, University of Colorado Denver, Aurora, CO 80045, USA. [email protected] [email protected].
PMID: 30404861 DOI: 10.1126/scitranslmed.aau4445
Abstract

Melanocortin-1 receptor (MC1R) is a molecular target for melanoma imaging and therapy because of its overexpression on rodent and human melanoma cells. Here, we evaluated the MC1R targeting and specificity of 68Ga-DOTA-GGNle-CycMSHhex and Cy5.5-GGNle-CycMSHhex using murine and human melanoma cells, and murine and xenografted tumors. 68Ga-DOTA-GGNle-CycMSHhex was used first in human as an imaging probe to evaluate the possibility of radionuclide therapy in patients with advanced-stage melanoma. 68Ga-DOTA-GGNle-CycMSHhex and Cy5.5-GGNle-CycMSHhex displayed MC1R-specific targeting properties in murine and human melanoma cells, as well as in murine melanoma and human melanoma-xenografted tumors. Both B16/F10 and M21 melanoma lesions could be easily imaged by positron emission tomography using 68Ga-DOTA-GGNle-CycMSHhex The first-in-human images of melanoma brain metastases in patients demonstrated the clinical relevance of MC1R as a molecular target for melanoma imaging, highlighting the potential of 68Ga-DOTA-GGNle-CycMSHhex as an MC1R-targeting melanoma imaging probe and underscoring the need to develop MC1R-targeting therapeutic agents for treating patients with metastatic melanoma.

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