The overall aim of the proposed renewal is to test, in preclinical and in clinical experiments, the safety and efficacy of iron- containing pharmaceuticals for obtaining added information from magnetic resonance imaging and spectroscopy.
The specific aims are threefold. First, study of newly selected agents will be undertaken by (a) screening selected paramagnetic iron chelates of hydroxamate, catecholate, phenolate and hydroxpyridonate ligands; and (b) exploring paramagnetic and superparamagnetic particulates. Second, continued study of selected agents from years 01-03 is proposed by (a) clinically measuring elimination, metabolic fate, and pharmacokinetics for agents from three biodistribution classes (ferrioxamine B, Fe-HBED, and magnetic AMI-25); (b) clinically assessing safety and efficacy of Fe-HBED and ferrioxamine B; (c) comparatively evaluating different enhancement agents for diagnosis of focal hepatic disease, and (d) comparatively evaluating efficacy of different relaxation agents for 31P MRS signal localization and enhancement. Third, the added benefit of T2, T2- and susceptibility-sensitive imaging techniques will be studied. By obtaining this data, progress will be made toward more complete understanding of magnetic resonance technology. Practical agents for image enhancement in several organ systems will be introduced. More refined uses, some previously considered poorly feasible, will be developed for spectroscopy and for tumor-, inflammation-, and flow-targeting. Investigative methods include (a) chemical synthesis and analysis; (b) pharmaceutical formulation and quality assurance; (c) nuclear magnetic resonance imaging, spectroscopy, and relaxometry; and (d) nuclear medicine radioanalogue detection methods.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038918-05
Application #
3177370
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1985-01-01
Project End
1990-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
White, D L (1991) Paramagnetic iron (III) MRI contrast agents. Magn Reson Med 22:309-12
Hoener, B; Engelstad, B L; Ramos, E C et al. (1991) Comparison of Fe-HBED and Fe-EHPG as hepatobiliary MR contrast agents. J Magn Reson Imaging 1:357-62
Muetterties, K A; Hoener, B A; Engelstad, B L et al. (1991) Ferrioxamine B derivatives as hepatobiliary contrast agents for magnetic resonance imaging. Magn Reson Med 22:88-100
Engelstad, B L; White, D L; Moseley, M E et al. (1990) Localization of P-31 MR signal with use of superparamagnetic iron oxide particles. Radiology 176:467-72
Weissleder, R; Stark, D D; Engelstad, B L et al. (1989) Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR Am J Roentgenol 152:167-73
Moseley, M E; White, D L; Wang, S C et al. (1989) Vascular mapping using albumin-(Gd-DTPA), an intravascular MR contrast agent, and projection MR imaging. J Comput Assist Tomogr 13:215-21
Engelstad, B L; White, D L; Huberty, J P et al. (1987) Hepatobiliary magnetic resonance contrast agents assessed by gadolinium-153 scintigraphy. Invest Radiol 22:232-8
Paajanen, H; Schmiedl, U; Aho, H J et al. (1987) Magnetic resonance imaging of experimental renal hemorrhage. Invest Radiol 22:792-8
Paajanen, H; Grodd, W; Revel, D et al. (1987) Gadolinium-DTPA enhanced MR imaging of intramuscular abscesses. Magn Reson Imaging 5:109-15
Marotti, M; Schmiedl, U; White, D et al. (1987) Metal chelates as urographic contrast agents for magnetic resonance imaging. A comparative study. Rofo 146:89-93

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