TY - JOUR
T1 - Short- vs. long-circulating magnetoliposomes as bone marrow-seeking MR contrast agents
AU - Bulte, Jeff W.M.
AU - De Cuyper, Marcel
AU - Despres, Daryl
AU - Frank, Joseph A.
PY - 1999/2
Y1 - 1999/2
N2 - We evaluated the relaxation enhancement and biodistribution of short- vs. long-circulating magnetoliposomes as a new contrast agent for magnetic resonance (MR) imaging of bone marrow. Magnetoliposomes with (ML-PEG) and without (ML) incorporation of polyethylene glycol (PEG, Mw 2000) were prepared, measuring 40 nm in diameter with 1-6 iron oxide crystals/vesicle. PEGylation selectively enhanced the T2 relaxivity of magnetoliposomes by 10% to 15%, with R1 and R2 values of 3 and 240 s-1/mM at 1.5 T and 37°C. ML (n = 6) and ML-PEG (n = 6) preparations were administered IV into young (6-8 weeks old) and adult (> 1 year old) Sprague-Dawley rats at 100 μmol Fe/kg. PEGylation increased blood half-life (P < 0.05 for t > 30 minutes), following a biexponential clearance with a long half-life of 53.2 ± 13.2 minutes. The clearance of ML was monoexponential, with a half-life 7.4 ± 0.4 minutes. MR imaging revealed a pronounced uptake in bone marrow, including the iliac bone, femur, tibia, and upper and lower vertebrae. The bone marrow uptake of ML-PEG was comparable to that of ML, with both reaching a plateau within 30 minutes following injection. Fast spin-echo T2-weighted imaging was found to provide optimal contrast enhancement and allowed a clear depiction of red to yellow marrow conversion due to normal aging. While the use of magnetoliposomes can provide the added benefit of therapeutic drug or gene delivery, further investigation is warranted to assess their usefulness in differentiating normal vs. abnormal marrow conditions.
AB - We evaluated the relaxation enhancement and biodistribution of short- vs. long-circulating magnetoliposomes as a new contrast agent for magnetic resonance (MR) imaging of bone marrow. Magnetoliposomes with (ML-PEG) and without (ML) incorporation of polyethylene glycol (PEG, Mw 2000) were prepared, measuring 40 nm in diameter with 1-6 iron oxide crystals/vesicle. PEGylation selectively enhanced the T2 relaxivity of magnetoliposomes by 10% to 15%, with R1 and R2 values of 3 and 240 s-1/mM at 1.5 T and 37°C. ML (n = 6) and ML-PEG (n = 6) preparations were administered IV into young (6-8 weeks old) and adult (> 1 year old) Sprague-Dawley rats at 100 μmol Fe/kg. PEGylation increased blood half-life (P < 0.05 for t > 30 minutes), following a biexponential clearance with a long half-life of 53.2 ± 13.2 minutes. The clearance of ML was monoexponential, with a half-life 7.4 ± 0.4 minutes. MR imaging revealed a pronounced uptake in bone marrow, including the iliac bone, femur, tibia, and upper and lower vertebrae. The bone marrow uptake of ML-PEG was comparable to that of ML, with both reaching a plateau within 30 minutes following injection. Fast spin-echo T2-weighted imaging was found to provide optimal contrast enhancement and allowed a clear depiction of red to yellow marrow conversion due to normal aging. While the use of magnetoliposomes can provide the added benefit of therapeutic drug or gene delivery, further investigation is warranted to assess their usefulness in differentiating normal vs. abnormal marrow conditions.
KW - Bone marrow
KW - Liposome
KW - MR imaging
KW - Superparamagnetic iron oxide
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U2 - 10.1002/(SICI)1522-2586(199902)9:2<329::AID-JMRI27>3.0.CO;2-Z
DO - 10.1002/(SICI)1522-2586(199902)9:2<329::AID-JMRI27>3.0.CO;2-Z
M3 - Article
C2 - 10077033
AN - SCOPUS:0033007218
SN - 1053-1807
VL - 9
SP - 329
EP - 335
JO - Journal of Magnetic Resonance Imaging
JF - Journal of Magnetic Resonance Imaging
IS - 2
ER -