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Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents
Final rept. 1 Sep 2008-31 Aug 2009
JOHNS HOPKINS HOSPITAL BALTIMORE MD
Pagination or Media Count:
We have synthesized and characterized MR imaging agents using hyaluronic acid HA polymer backbones with molecular weights of 16, 31, and 74 kDa. The gadolinium content of HA-EDA-DTPA-Gd conjugates varied with preparations and was about 10 as determined by ICP-MS, which corresponds to 70 modification ratio of the HA carboxyl groups. T1 values of HA-EDA-DTPA-Gd prepared from HA of molecular weight 16kD, 31kD, and 74kD and measured at 400MHz were very comparable in the range from 15.3 ms to 19 ms. We also synthesized fluorescent labeled HA probes using the same HA molecules and demonstrated efficient labeling of the polymer using anime-reactive dyes and EDCEDA linker. Biodistribution of the HA-EDA-DTPA-Gd contrast agent in vivo was determined by T1 weighted MRI. Blood half-life time of HA-EDA-DTPA-Gd compounds was determined from changes in blood relaxivity as a function of time. Two-compartment pharmacokinetic model provided good fit of experimental data and for 16kDa HA compound the fast and slow phases life times were 12.4 min and 141 min, respectively. Preliminary data suggest an increased uptake of 16 kDa and 31 kDa HA-EDADTPA-Gd agents in CD44-positive MDA-MB-231 tumor xenografts in comparison to CD44-negative MCF-7 tumors.
APPROVED FOR PUBLIC RELEASE