MEDI 64 |
| The extracellular pH of solid human tumors is often 0.4 units lower than normal healthy tissue. A pH-switchable MRI probe that “turns on” in lower pH conditions may improve tumor detection. For example, the relaxivity of a pH-sensitive contrast agent, GdDOTA-4AmP, rises from 3.8 to 10 mM-1s-1 on passing from pH 9.6 to 6.0. To obtain a greater increase in relaxivity, an analogue of p-SCN-Bn-DOTA-4AmP has been conjugated to the amines surface of a G5-PAMAM dendrimer, and the relaxivity of the gadolinium-loaded G5-PAMAM dendrimer increased from 11 mM-1s-1 to 24 mM-1s-1 on passing from pH 9.5 to 6.0. We have conjugated the same analogue to biotinylated G5-PAMAM dendrimer that can interact with steptavidin to passively target the dendritic MRI probe to the liver. The Biotin-G5-GdDOTA-4AmP-streptavidin conjugate is being investigated within an in vivo hepatocarcinoma woodchuck model to map liver pH and improve detection of liver tumors. |
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General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Division of Medicinal Chemistry |