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PET imaging of leptin biodistribution and metabolism in rodents and primates

Official URL:https://doi.org/10.1016/j.cmet.2009.07.001
PubMed:View item in PubMed
Creators Name:Ceccarini, G. and Flavell, R.R. and Butelman, E.R. and Synan, M. and Willnow, T.E. and Bar-Dagan, M. and Goldsmith, S.J. and Kreek, M.J. and Kothari, P. and Vallabhajosula, S. and Muir, T.W. and Friedman, J.M.
Journal Title:Cell Metabolism
Journal Abbreviation:Cell Metab
Volume:10
Number:2
Page Range:148-159
Date:6 August 2009
Keywords:Humdisease, Fluorine Radioisotopes, Gallium Isotopes, 1-Ring Heterocyclic Compounds, Kidney Tubules, LDL-Receptor Related Protein 2, Leptin, Obesity, Positron-Emission Tomography, Leptin Receptors, Tissue Distribution, Whole Body Imaging, Animals, Mice, Rats, Macaca Mulatta
Abstract:We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using (18)F- and (68)Ga-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 (18)F labeling of proteins for PET imaging of other polypeptide hormones.
ISSN:1550-4131
Publisher:Cell Press (U.S.A.)
Item Type:Article

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