PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates |
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| Authors: | 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 |
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| Affiliation: | 1 Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA;2 Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, NY 10065, USA;3 Laboratory on the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA;4 Citigroup Biomedical Imaging Center, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA;5 Max-Delbrueck Center for Molecular Medicine, Berlin, Germany |
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| 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. |
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| Keywords: | HUMDISEASE |
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