A fluorinated dendrimer-based nanotechnology platform: new contrast agents for high field imaging.
OBJECTIVE
We aimed to develop a directly detected magnetic resonance imaging (MRI) contrast agent for use with high fields based on a nanoscale fluorinated dendrimer-based platform for F MRI and overcome some of the problems with F MRI.


METHODS
The dendrimers were prepared in a convergent manner by making the appropriate dendron, followed by coupling to a central core. The dendrons were prepared by attaching 3 equivalents of the fluorinated amino acid to the 3 carboxylic acids of the repeat branch unit followed by deprotection of the amine branch point, and either coupling to another repeat branch unit (increasing the generation G) or used directly allowing the precise growth of the dendrimer. The size of the dendrimers was determined by diffusion nuclear magnetic resonance (NMR) spectroscopy. The toxicity of the dendrimers was measured using the MTT assay. Fluorine longitudinal relaxation time measurements were performed on a Bruker ACP-500 NMR using a saturation recovery experiment at 470.59 MHz frequency. Healthy 150 g Sprague-Dawley female rats were imaged using a dendrimer solution.


RESULTS
The size of the dendrimers is generally less than 3 nm, 2 orders of magnitude smaller than the size of the perfluorocarbon nanoparticles (about 200 nm). The longitudinal relaxation time, T1, decreases with increasing dendrimer generation. A significant improvement in relaxation rate and signal-to-noise ratio can be achieved by either the chemical modification of the dendrimer with a gadolinium-chelate or by the physical addition of exogenous contrast agent. Although the dendrimers with fluorine in the surface layer are toxic, this toxicity is easily reduced by burying the fluorine further into the dendrimer interior. (19)F MR images of the rat using the dendrimer solution were rapidly obtained at 7 Tesla, the strong contrast in the heart generated by the dendrimer can be seen.


CONCLUSIONS
A novel fluorinated dendrimer-based nanotechnology platform in (19)F MRI and a new bifunctional DOTA chelate were prepared and characterized. We introduce 2 methods for reducing the (19)F longitudinal relaxation time: (a) Increasing the generation; (b) covalent and noncovalent introduction of Gd(III)-chelates. A new bifunctional Gd(III)-chelate is presented. The investigations of imaging on rats suggest potential importance of the dendrimers in (19)F MRI application.
Huang
Zhihua
Z
Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Sengar
Raghvendra S
RS
Nigam
Archana
A
Abadjian
Marie-Caline
MC
Potter
Douglas M
DM
Grotjahn
Douglas B
DB
Wiener
Erik C
EC
D000818:Animals; D003287:Contrast Media; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D054879:Halogenation; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D003287:Contrast Media; D050091:Dendrimers; D005466:Fluorocarbons; D005682:Gadolinium