89Zr-labeled dextran nanoparticles allow in vivo macrophage imaging.
Tissue macrophages play a critical role both in normal physiology and in disease states. However, because of a lack of specific imaging agents, we continue to have a poor understanding of their absolute numbers, flux rates, and functional states in different tissues. Here, we describe a new macrophage specific positron emission tomography imaging agent, labeled with zirconium-89 ((89)Zr), that was based on a cross-linked, short chain dextran nanoparticle (13 nm). Following systemic administration, the particle demonstrated a vascular half-life of 3.9 h and was found to be located primarily in tissue resident macrophages rather than other white blood cells. Subsequent imaging of the probe using a xenograft mouse model of cancer allowed for quantitation of tumor-associated macrophage numbers, which are of major interest in emerging molecular targeting strategies. It is likely that the material described, which allows the visualization of macrophage biology in vivo, will likewise be useful for a multitude of human applications.
Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
Edmund J
EJ
Keliher
Jeongsoo
J
Yoo
Matthias
M
Nahrendorf
Jason S
JS
Lewis
Brett
B
Marinelli
Andita
A
Newton
Mikael J
MJ
Pittet
Ralph
R
Weissleder
D000818:Animals; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007554:Isotopes / Q000032:analysis; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods*; D015040:Zirconium / Q000032:analysis
D003911:Dextrans; D007554:Isotopes; D015040:Zirconium