Biodegradation of magnetite dextran nanoparticles in the rat. A histologic and biophysical study.
BACKGROUND
Superparamagnetic iron oxide particles represent a new class of contrast agents that increase the detectability of hepatic and splenic tumors by magnetic resonance imaging (MRI). Magnetite dextran nanoparticles, a preparation with a small mean particle diameter in solution and null zêta potential present high safety margin and efficacy. The purpose of this investigation was to define the main steps of the metabolism of the iron oxide crystals.


METHODS
Rats were intravenously administered a single small dose of 59Fe-labeled MD3 (3 mg Fe/kg), and the biodistribution of 59Fe was investigated in the different organs from 2 hours to 25 days postinjection. Magnetic susceptibility studies were conducted in parallel to light microscopy and immunohistochemistry from day 1 to day 14 after administration.


RESULTS
Most of the dose accumulated in the carcass (45%), liver (7%), and spleen (7%) in the first 2 hours. In the spleen, a continuously iron uptake was observed up to 48 hours (44%), then decreased to 25 days (22%). The splenic magnetic susceptibility dropped sharply during the first days and then more slightly until day 14. In the liver and blood, the 59Fe-level decreased at 24 hours and then increased until day 25 (11% and 27%, respectively). Histochemistry features essentially confirmed the radiotracer data and showed that iron oxide cores were accumulated into the Kupffer cells and the macrophages of the splenic marginal zone. With time, the number of the granules was decreased whereas the fine iron granules appeared in the cytoplasm. Immunopositive staining for ferritin was markedly increased in the liver hepatocytes to 3 days after injection, and in the splenic marginal zone macrophages to 14 days after injection.


CONCLUSIONS
The data point to the early biodegradation of the iron oxide crystals. MD3 thus appear as an interesting biodegradable new contrast agent first devoted to magnetic resonance imaging of liver and spleen diseases that could be further extended to heart, kidneys, and other organs.
Okon
E
E
Laboratoire de Biophysique, Faculté de Médecine, Angers, France.
Pouliquen
D
D
Okon
P
P
Kovaleva
Z V
ZV
Stepanova
T P
TP
Lavit
S G
SG
Kudryavtsev
B N
BN
Jallet
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001673:Biodegradation, Environmental; D003287:Contrast Media / Q000378:metabolism* / Q000493:pharmacokinetics; D003911:Dextrans; D005293:Ferritins / Q000378:metabolism; D052203:Ferrosoferric Oxide; D007124:Immunoenzyme Techniques; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D007504:Iron Radioisotopes; D008099:Liver / Q000378:metabolism / Q000473:pathology; D058185:Magnetite Nanoparticles; D008297:Male; D010087:Oxides / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D003911:Dextrans; D007504:Iron Radioisotopes; D058185:Magnetite Nanoparticles; D010087:Oxides; D005293:Ferritins; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide