3D-micro-MR angiography of mice using macromolecular MR contrast agents with polyamidoamine dendrimer core with reference to their pharmacokinetic properties.
Four novel macromolecular MRI contrast agents, all of which had the same chemical composition but different molecular weights, were prepared using generation-3, -4, -5, and -6 polyamidoamine (PAMAM) dendrimers conjugated with a bifunctional diethylenetriaminepentaacetic acid derivative to change the blood retention, tissue perfusion, and excretion. Size-dependent changes in the pharmacokinetics were observed in the biodistribution study. (153)Gd-labeled generation-6 PAMAM-conjugates remained in the blood significantly longer than all of the other preparations (P < 0.001). The increase in blood-to-organ ratio of the preparations was found to correlate with increasing molecular size (P < 0.001). Additionally, 3D-micro MR images and angiography of mice of high quality and detail were obtained using PAMAM-(1B4M-Gd)x as a macro-molecular MRI contrast agent with a 1.5-T clinical MRI instrument. Numerous fine vessels of approximately 200 microm diameter were visualized on subtracted 3D-MR angiographms with G6D-(1B4M-Gd)(192). The quality of the images was sufficient to estimate the microvasculature of cancerous tissue for anti-angiogenesis therapy and to investigate knockout mice. Magn Reson Med 45:454-460, 2001.
Department of Diagnostic and Interventional Imagiology, Graduate Schoool of Medicine, Kyoto University, Kyoto, Japan. hisataka@kuhp.kyoto-u.ac.jp
H
H
Kobayashi
N
N
Sato
A
A
Hiraga
T
T
Saga
Y
Y
Nakamoto
H
H
Ueda
J
J
Konishi
K
K
Togashi
M W
MW
Brechbiel
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005029:Ethylenediamines / Q000493:pharmacokinetics*; D005260:Female; D021621:Imaging, Three-Dimensional; D046911:Macromolecular Substances; D018810:Magnetic Resonance Angiography; D051379:Mice; D008819:Mice, Nude; D011073:Polyamines / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D003287:Contrast Media; D004338:Drug Combinations; D005029:Ethylenediamines; D046911:Macromolecular Substances; D011073:Polyamines