Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging.
An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging.
Weissleder
R
R
Department of Radiology, Massachusetts General Hospital, Boston.
Elizondo
G
G
Wittenberg
J
J
Rabito
C A
CA
Bengele
H H
HH
Josephson
L
L
D000818:Animals; D002199:Capillary Permeability; D002478:Cells, Cultured; D003287:Contrast Media; D004730:Endothelium, Vascular / Q000378:metabolism; D052203:Ferrosoferric Oxide; D007501:Iron / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010087:Oxides; D010316:Particle Size; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D003287:Contrast Media; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide