PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates

被引：47

作者：

Ceccarini, Giovanni ^{[2
]}

Flavell, Robert R. ^{[1
]}

Butelman, Eduardo R. ^{[3
]}

Synan, Michael ^{[4
]}

Willnow, Thomas E. ^{[5
]}

Bar-Dagan, Maya ^{[1
]}

Goldsmith, Stanley J. ^{[4
]}

Kreek, Mary J. ^{[3
]}

Kothari, Paresh ^{[4
]}

Vallabhajosula, Shankar ^{[4
]}

Muir, Tom W. ^{[1
]}

Friedman, Jeffrey M. ^{[2
]}

机构：

[1] Rockefeller Univ, Lab Synthet Prot Chem, New York, NY 10065 USA

[2] Rockefeller Univ, Howard Hughes Med Inst, Mol Genet Lab, New York, NY 10065 USA

[3] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10065 USA

[4] Cornell Univ, Weill Cornell Med Coll, Citigrp Biomed Imaging Ctr, New York, NY 10065 USA

[5] Max Delbrueck Ctr Mol Med, Berlin, Germany

来源：

CELL METABOLISM | 2009年 / 10卷 / 02期

关键词：

HEMATOPOIETIC-CELLS; IN-VIVO; RECEPTOR; MEGALIN; OBESITY; KIDNEY; BRAIN; MICE; PROLIFERATION; TRANSPORT;

D O I：

10.1016/j.cmet.2009.07.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using F-18- and Ga-68-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 F-18 labeling of proteins for PET imaging of other polypeptide hormones.

引用

页码：148 / U7

页数：11

共 35 条

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