The goals of this project have been to design, synthesize and evaluate new compounds as potential organ- or tumor-imaging agents. Pharmacological and biochemical principles have served as the basis for achieving site-specific delivery of these agents. Current research is focused on the synthesis of radioiodinated and polyiodinated analogs of naturally-occurring lipids as potential scintigraphic agents and radiopaques, respectively. Of especial interest are iodinated analogs of fatty acids, acylcarnitines, sterol esters, diacyglycerides, triglycerides, phospholipid ethers, and phospholipids. The target compounds will be designed so as to provide information not only on the ability of these agents to accumulate in specific tissues but also on their capacity to participate in biochemical transformations peculiar to such tissues. Accordingly, such probes offer the potential of furnishing a noninvasive means for ascertaining both organ structure and function. All new agents will be labeled with iodine-125 for initial biodistribution studies in normal rats. Promising agents will then be followed up by Gamma-camera scintigraphy and computed tomography in the appropriate rat or rabbit model. Selected agents will also be incorporated into natural or reconstituted lipoproteins in order to capitalize on the known biodistribution properties of these macromolecular vesicles. Such research holds significant promise for the eventual development of new radiologic agents for the diagnosis of various hepatic, endocrine, and cardiovascular disorders.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA008349-21
Application #
3163304
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1979-05-01
Project End
1990-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
21
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Plotzke, K P; Fisher, S J; Wahl, R L et al. (1993) Selective localization of a radioiodinated phospholipid ether analog in human tumor xenografts. J Nucl Med 34:787-92
Plotzke, K P; Rampy, M A; Meyer, K et al. (1993) Biodistribution, metabolism, and excretion of radioiodinated phospholipid ether analogs in tumor-bearing rats. J Nucl Biol Med 37:264-72
Schwendner, S W; Weichert, J P; Longino, M A et al. (1992) Potential organ or tumor imaging agents. 32. A triglyceride ester of p-iodophenyl pentadecanoic acid as a potential hepatic imaging agent. Int J Rad Appl Instrum B 19:639-50
Plotzke, K P; Haradahira, T; Stancato, L et al. (1992) Selective localization of radioiodinated alkylphosphocholine derivatives in tumors. Int J Rad Appl Instrum B 19:765-73
Deforge, L E; Degalan, M R; Ruyan, M K et al. (1992) Comparison of methods for incorporating a radioiodinated residualizing cholesteryl ester analog into low density lipoprotein. Int J Rad Appl Instrum B 19:775-82
DeForge, L E; Ruyan, M K; Schwendner, S W et al. (1991) Synthesis and evaluation of radioiodinated cholesteryl ethers as lipoprotein probes. Bioconjug Chem 2:254-60
Freeman, D A; Counsell, R E (1991) Cellular internalization, transport, and esterification of iodine-125-NP59 by MA-10 Leydig tumor cells. J Nucl Med 32:495-9
Counsell, R E; Schwendner, S W; DeForge, L E et al. (1991) Lipoproteins as carriers for organ-imaging radiopharmaceuticals. Targeted Diagn Ther 5:251-314
Counsell, R E; Schwendner, S W; Meyer, K L et al. (1990) Tumor visualization with a radioiodinated phospholipid ether. J Nucl Med 31:332-6
Van Dort, M; Santay, L; Schwendner, S W et al. (1989) Potential tumor or organ imaging agents--31. Radioiodinated sterol benzoates and carbamates. Int J Rad Appl Instrum B 16:603-7

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