The primary objective of this research is the development of new, efficacious, myocardial perfusion imaging agents based on the chemistry and nuclear properties of 99m-Tc. This will be accomplished by merging the techniques, equipment and expertise of inorganic chemistry with those of nuclear medicine. Emphasis will be on (1) elucidation of the inorganic chemistry of technetium, utilizing the relatively stable isotope 99-Tc and physical techniques such as single crystal x-ray diffraction and thin-layer spectroelectrochemistry which require only very small quantities of sample, (2) development of synthetic routes to 99m-Tc radiopharmaceuticals that do not involve Sn(II) reduction, (3) development of 99m-Tc myocardial perfusion imaging agents based on well defined, monocationic technetium complexes, (4) elucidation of the chemistry and mechanism of action of those monocationic 99m-Tc myocardial perfusion imaging agents recently developed within this project, e.g. (99m-Tc(dmpe)2Cl2)+ and (99m-Tc(dmpe)3)+ where dmpe = 1,2-bis(dimethylphosphine)ethane, (5) development of in vitro screening procedures to aid in selecting which monocationic 99m-Tc complexes warrant extensive in vivo evaluation, and (6) design and synthesis of new classes of technetium radiopharmaceuticals, the molecular and chemical properties of which can be subtly and systematically modified in order to increase specificity for the myocardium. Animal testing, including the imaging of dogs with induced acute myocardial infarction, will be used to evaluate the efficacy of new radiopharmaceuticals and thereby delineate those molecular and chemical properties than enhance myocardial uptake. The most promising myocardial perfusion imaging agents will be evaluated in human subjects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL021276-09
Application #
3336440
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1977-09-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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Gerson, M C; Lukes, J; Deutsch, E et al. (1994) Comparison of technetium-99m-Q3 and thallium-201 for detection of coronary artery disease in humans. J Nucl Med 35:580-6
Gerson, M C; Millard, R W; Roszell, N J et al. (1994) Kinetic properties of 99mTc-Q12 in canine myocardium. Circulation 89:1291-300
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Zhou, T Z; Hirth, W W; Heineman, W R et al. (1988) Quantitative HPLC determination of [99mTc]-pertechnetate in radiopharmaceuticals and biological samples--I. Technique development. Int J Rad Appl Instrum B 15:493-8
Deutsch, E; Hirth, W (1987) In vivo inorganic chemistry of technetium cations. J Nucl Med 28:1491-500
Deutsch, E; Vanderheyden, J L; Gerundini, P et al. (1987) Development of nonreducible technetium-99m(III) cations as myocardial perfusion imaging agents: initial experience in humans. J Nucl Med 28:1870-80
Deutsch, E; Libson, K; Vanderheyden, J L et al. (1986) The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine. Int J Rad Appl Instrum B 13:465-77