SYNTHESIS & CHARACTERIZATION OF NEW MACROMOLECULAR CONTRAST AGENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Imaging contrast agents (or contrast media) are a category of diagnostic pharmaceuticals for enhancing the image contrast of organs/tissues and for displaying the organ function in medical imaging. Macromolecular contrast agents have found their important role in the characterization of microvascular permeability/leakiness of tumor vessels, due to their blood-pool characteristics. New polyethyleneglycol (PEG)-core dendrimeric contrast agents with well-defined structure, high degree of size homogeneity, synthetic flexibility, and high effectiveness in imaging, have been synthesized. Their average molecular weights (MW) and MW distribution will be obtained from mass spectrometry, which info will be highly valuable for the study of their structure-property relationship and for the guidance of our synthetic optimization. In addition, those new small molecular intermediates, which are attributed to the image contrast, need the structure characterization by mass spectrometry. For different macromolecular derivatives (MW 3,000 - 90,000), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry is used for the measurements of their MW and MW distributions. For small molecular compounds (MW 100 - 2000), electron spray ionization (ESI) mass spectrometry is applicable. Mass spectra data will be correlated with the data from physical and imaging measurements, the relationship among chemical, physical and imaging properties will be sought for this new class of dendrimeric contrast agents. The mass spectra data are highly important and valuable in the synthesis of our new PEG-core dendrimeric contrast agents for cancer imaging.