The underlying mechanisms of proton relaxation enhancement by endogenous (ferritin, hemosiderin) and administered (superparamagnetic) ferric iron oxides, ferric oxyhydroxides, reconstituted artificial ferritin, dendrimers, and liposomes are being investigated. The major focus of the research this year has been on the Star Burst tm dendrimers particularly Dysprosium-DOTA-PAMAM, Generation (G) = 5 dendrimers and biotinylated Gadolinium-DTPA-PAMAM, G=5 dendrimers, with between 70 and 80 metal atoms attached. The underlying contrast mechanisms were evaluated in these two compounds in regards to their relative effects on the T1 and T2 relaxation times in solution--at variable field strengths and temperatures. There is a strikingly large dependence of T2 on the inner sphere exchange time, not only for the dysprosium dendrimers, but also for the single ionic dysprosium chelates Dy-DTPA and Dy-DOTA. The quadratic dependence with field, which was greater at lower temperatures, was predicted and has now been experimentally verified. It is basically derived from the inner sphere susceptibility term (Curie's term). The implication is that small changes in the exchange time (by chemically modifying some of the outer side groups) may lead to dramatic improvements of T2 proton relaxation enhancement. For the gadolinium chelated dendrimers, we observed a secular component for T2, with an R2 of 39 mM-1sec-1 at 37C and 1.5 T. In contrast, 1/T1 initially increased with field strength but then decreased to 24 mM-1sec-1. The implication is that when using these dendrimers at higher field strengths (e.g. 4.7 T), T2 will be predominantly shorted with little effect on T1, which should be an advantage when using T2-sensitive MR imaging techniques while maintaining high signal to noise (long T1's). By understanding the relaxation properties of dendrimers,we would like to explore the possibly of using these agents as cell specific markers. In particular, we plan to biotinylate these agents and then attach MoAb through a streptavidin complex and use the contrast agent to target specific receptors on endothelial cells or other tissues.
| Shen, Diandian; Pan, Min-Hsiung; Wu, Qing-Li et al. (2011) A rapid LC/MS/MS method for the analysis of nonvolatile antiinflammatory agents from Mentha?spp. J Food Sci 76:C900-8 |
| Shen, Diandian; Pan, Min-Hsiung; Wu, Qing-Li et al. (2010) LC-MS method for the simultaneous quantitation of the anti-inflammatory constituents in oregano (Origanum species). J Agric Food Chem 58:7119-25 |
