PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates

Giovanni Ceccarini, Robert R. Flavell, Eduardo R. Butelman, Michael Synan, Thomas E. Willnow, Maya Bar-Dagan, Stanley J. Goldsmith, Mary J. Kreek, Paresh Kothari, Shankar Vallabhajosula, Tom W. Muir, Jeffrey M. Friedman

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using 18F- and 68Ga-labeled leptin revealed that, in mouse, the hormone was rapidly taken up by megalin (gp330/LRP2), a multiligand endocytic receptor localized in renal tubules. In addition, in rhesus monkeys, 15% of labeled leptin localized to red bone marrow, which was consistent with hormone uptake in rodent tissues. These data confirm a megalin-dependent mechanism for renal uptake in vivo. The significant binding to immune cells and blood cell precursors in bone marrow is also consistent with prior evidence showing that leptin modulates immune function. These experiments set the stage for similar studies in humans to assess the extent to which alterations of leptin's biodistribution might contribute to obesity; they also provide a general chemical strategy for 18F labeling of proteins for PET imaging of other polypeptide hormones.

Original languageEnglish (US)
Pages (from-to)148-159
Number of pages12
JournalCell Metabolism
Volume10
Issue number2
DOIs
StatePublished - Aug 6 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Keywords

  • HUMDISEASE

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    Ceccarini, G., Flavell, R. R., Butelman, E. R., Synan, M., Willnow, T. E., Bar-Dagan, M., Goldsmith, S. J., Kreek, M. J., Kothari, P., Vallabhajosula, S., Muir, T. W., & Friedman, J. M. (2009). PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates. Cell Metabolism, 10(2), 148-159. https://doi.org/10.1016/j.cmet.2009.07.001