Abstract

The goal of this project is the development of new and improved radiopharmaceuticals labeled with generator-produced radionuclides (Ga-68, Cu-62, Tc-99m) for use in diagnostic nuclear medicine. Major emphasis will be placed on the preparation of tracers for non-invasive evaluation of regional cerebral and myocardial blood flow. New compounds of these elements, possessing properties believed important in achieving the desired in vivo behavior, will be synthesized and characterized at macroscopic concentrations (10-3 - 10-1M) using conventional chemical techniques. Radiolabeled compounds of these nuclides will then be prepared and characterized, with chromatographic techniques being employed to correlate chemistry at the no-carrier-added level with that defined at macroscopic concentrations. The potential of these radiolabeled compounds to serve as useful radiopharmaceuticals will be evaluated by biodistribution studies in rats. Compounds showing adequate uptake in organs of interest will be investigated in greater detail in larger animals (dogs). Suitability for organ imaging will be determined and comparisons with accepted tracers then employed to assess the physiological significance of the images obtained.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL001801-04
Application #
3074070
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1987-08-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Type
Schools of Pharmacy
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Ter-Pogossian, M M; Ficke, D C; Beecher, D E et al. (1994) The super PET 3000-E: a PET scanner designed for high count rate cardiac applications. J Comput Assist Tomogr 18:661-9
Mathias, C J; Welch, M J; Green, M A et al. (1991) In vivo comparison of copper blood-pool agents: potential radiopharmaceuticals for use with copper-62. J Nucl Med 32:475-80
Barnhart-Bott, A; Green, M A (1991) The effects of glutathione depletion on the biodistribution of Cu(PTSM) in rats. Int J Rad Appl Instrum B 18:865-9
Mathias, C J; Margenau, W H; Brodack, J W et al. (1991) A remote system for the synthesis of copper-62 labeled Cu(PTSM). Int J Rad Appl Instrum A 42:317-20
Mathias, C J; Welch, M J; Perry, D J et al. (1991) Investigation of copper-PTSM as a PET tracer for tumor blood flow. Int J Rad Appl Instrum B 18:807-11
Green, M A (1990) The potential for generator-based PET perfusion tracers. J Nucl Med 31:1641-5
Shelton, M E; Green, M A; Mathias, C J et al. (1990) Assessment of regional myocardial and renal blood flow with copper-PTSM and positron emission tomography. Circulation 82:990-7
Mathias, C J; Welch, M J; Raichle, M E et al. (1990) Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM. J Nucl Med 31:351-9
Green, M A; Mathias, C J; Welch, M J et al. (1990) Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion. J Nucl Med 31:1989-96
John, E K; Green, M A (1990) Structure-activity relationships for metal-labeled blood flow tracers: comparison of keto aldehyde bis(thiosemicarbazonato)copper(II) derivatives. J Med Chem 33:1764-70

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