Short- vs. long-circulating magnetoliposomes as bone marrow-seeking MR contrast agents

We evaluated the relaxation enhancement and biodistribution of short- vs. l ong-circulating magnetoliposomes as a new contrast agent for magnetic reson ance (MR) imaging of bone marrow. Magnetoliposomes with (ML-PEG) and withou t (ML) incorporation of polyethylene glycol (PEG, Mw 2000) were prepared, m easuring 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 degrees 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 mu mol Fe/kg , PEGylation increased blood half-life (P < 0.05 for t > 30 minutes), follo wing a biexponential clearance with a long half-life of 53.2 +/- 13.2 minut es. The clearance of ML was monoexponential, with a half-life 7.4 +/- 0.4 m inutes. MR imaging revealed a pronounced uptake in bone marrow, including t he iliac bone, femur, tibia, and upper and lower vertebrae. The bone marrow uptake of ML-PEG was comparable to that of MI,, with both reaching a plate au within 30 minutes following injection. Fast spin-echo Ta-weighted imagin g was found to provide optimal contrast enhancement and allowed a clear dep iction of red to yellow marrow conversion due to normal aging. While the us e of magnetoliposomes can provide the added benefit of therapeutic drug or gene delivery, further investigation is warranted to assess their usefulnes s in differentiating normal vs. abnormal marrow conditions, J. Magn. Reson. Imaging 1999;9:329-335, (C) 1999 Wiley-Liss, Inc.