TY - JOUR
T1 - PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates
AU - Ceccarini, Giovanni
AU - Flavell, Robert R.
AU - Butelman, Eduardo R.
AU - Synan, Michael
AU - Willnow, Thomas E.
AU - Bar-Dagan, Maya
AU - Goldsmith, Stanley J.
AU - Kreek, Mary J.
AU - Kothari, Paresh
AU - Vallabhajosula, Shankar
AU - Muir, Tom W.
AU - Friedman, Jeffrey M.
N1 - Funding Information:
We would like to acknowledge Professor Allyn Mark for the helpful discussion and critical reading of the manuscript, Simon Morim for technical support with the clinical scanner, and Susan Koress for assistance in compiling this manuscript. This work was supported by funds from NIH grants GM072015 (T.W.M.) and GM55843 (T.W.M.), the Picower Foundation (G.C. and J.M.F.), and the Howard Hughes Medical Institute (J.M.F.). R.F. was supported by NIH MSTP grant GM07739.
PY - 2009/8/6
Y1 - 2009/8/6
N2 - 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.
AB - 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.
KW - HUMDISEASE
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U2 - 10.1016/j.cmet.2009.07.001
DO - 10.1016/j.cmet.2009.07.001
M3 - Article
C2 - 19656493
AN - SCOPUS:67849124642
SN - 1550-4131
VL - 10
SP - 148
EP - 159
JO - Cell Metabolism
JF - Cell Metabolism
IS - 2
ER -