PET imaging of leptin biodistribution and metabolism in rodents and primates.
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.
Ceccarini
Giovanni
G
Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Flavell
Robert R
RR
Butelman
Eduardo R
ER
Synan
Michael
M
Willnow
Thomas E
TE
Bar-Dagan
Maya
M
Goldsmith
Stanley J
SJ
Kreek
Mary J
MJ
Kothari
Paresh
P
Vallabhajosula
Shankar
S
Muir
Tom W
TW
Friedman
Jeffrey M
JM
D000818:Animals; D005462:Fluorine Radioisotopes; D005709:Gallium Isotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D020738:Leptin / Q000032:analysis / Q000493:pharmacokinetics*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000175:diagnosis; D049268:Positron-Emission Tomography; D011859:Radiography; D051381:Rats; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D051598:Whole Body Imaging
D005462:Fluorine Radioisotopes; D005709:Gallium Isotopes; D006573:Heterocyclic Compounds, 1-Ring; D020738:Leptin; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D054411:Receptors, Leptin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid