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.

Rationale and Objectives: The purpose of this study was establish the ability of cadence pulse sequencing (CPS), a novel ultrasound contrast sequence, to detect changes in renal blood flow induced by the administration of vasoactive substances in rats. Materials and Methods: Twelve adult male Fischer 344 rats were used in this study. Rats were anesthetized and a catheter was placed in the tail vein. Ultrasound contrast media (Definity) was administered as a constant rate infusion (130 ml/ml, 60 ml/min) and CPS data acquired from the right kidney. Real-time motion correction was applied and parametric images were generated based on the CPS data sets. Rats were then randomly assigned to one of two groups such that Group 1 rats (n ¼ 8) were administered a vasodilator (Hydralazine, 5 mg/kg i.v.) and Group 2 rats (n ¼ 4) were given a vasoconstrictor (Dopamine, 10 mg/kg/ min i.v.). CPS imaging of the kidney was repeated following ample time for drug effects to occur. Measurement of renal blood flow was obtained at baseline and after each vasoactive drug was administered. The percentage change from baseline was calculated. Results: Contrast CPS was able to define statistically significant differences between pre-drug and post-drug blood flow in the renal medulla (hydralizine, p < 0.01; dopamine, p < 0.0001). Contrast CPS was able to define statistically significant differences between pre-drug and post-drug blood flow in the renal cortex for dopamine (p <<< 0:0001). Conclusions:Contrast CPS ultrasound appears capable of estimating renal blood flow in rats. Vasoactive substances induce detectable changes in the blood flow parameter. This technique may prove useful for the assessment of regional vascular parameters in kidneys, tumors and other tissues. Acknowledgements: The support of NIH CA 76062 and the assistance of James Chomas, Dennis Paul and Sean Mhanna are gratefully acknowledged. (Figure 1) consists of paired dendritic polylysines, initiated from both ends of a poly(ethylene glycol) (PEG) core yielding an array of multiple free amino groups for conjugation with gadolinium (Gd) chelates for MRI. We hypothesize that the best-selected candidate compound in this design will be able to yield primarily intravascular distribution, complete and timely whole body clearance, in vivo near monodispersity, high effectiveness (T 1 relaxivity) and a good safety profile. The immediate goal is to select the optimal candidate compound for advancement to clinical trials for applications in cancer microvascular characterizations and blood pool imaging. Methods: Dendritic polylysines were synthesized using t-butyloxycarbonyl (t-Boc) peptide chemistry in a divergent manner. The openchain ligand DTPA, or the macrocylclic ligand GlyMeDOTA (a gift from Bayer Schering Pharma), was conjugated to these dendrimers via N-hydroxysuccinimidyl ester method. Subsequent chelation with Gd ions was conducted to yield two series of PEG-core dendrimeric contrast agents. Their chemical, physical, kinetic and certain biological properties, including s...