Abstract

The major objective of this project is to develop new radiopharmaceuticals specific for imaging CNS dopamine receptors. In conjunction with single photon emission computed tomography (SPECT), the proposed dopamine specific agents may provide a convenient tool for measuring the dopamine receptor population. Therefore, it may improve our understanding on the progression and also on the management of this disease. Two dopamine receptor specific agents; (125I) IBZP and (125I) IBZM, specific for D-1 and D-2 dopamine receptor, respectively, have been prepared and evaluated in rats. The digital autoradiography study showed that after an iv injection in rats, these two agents localized in caudate-putamen, substantia nigra, and accumbens nucleus, areas of brain known to have high concentration of D-1 and D-2 receptors. Based on the preliminary data, we propose to synthesize the optically active isomers of IBZM and IBZP and their analogs, study the radiochemistry and kit formulation, and evaluate digital autoradiography using multiple isotopes (I-123 and I-125) with both normal and parkinsonian (MPTP treated) animal models in mice and monkeys. For two promising compounds, toxicity data will be obtained and they may be evaluated in humans by the SPECT imaging. These new dopamine receptor imaging agents may provide a convenient and non-invasive technique for evaluation of parkinsonian patients. The diagnostic information obtained with these agents may not be attainable through other diagnostic techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS024538-02
Application #
3409242
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1987-05-01
Project End
1990-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Acton, Paul D; Hou, Catherine; Kung, Mei-Ping et al. (2002) Occupancy of dopamine D2 receptors in the mouse brain measured using ultra-high-resolution single-photon emission tomography and [123]IBF. Eur J Nucl Med Mol Imaging 29:1507-15
Kung, H F (2001) Development of Tc-99m labeled tropanes: TRODAT-1, as a dopamine transporter imaging agent. Nucl Med Biol 28:505-8
Kung, H F; Lee, C W; Zhuang, Z P et al. (2001) Novel stilbenes as probes for amyloid plaques. J Am Chem Soc 123:12740-1
Mozley, L H; Gur, R C; Mozley, P D et al. (2001) Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry 158:1492-9
Acton, P D; Meyer, P T; Mozley, P D et al. (2000) Simplified quantification of dopamine transporters in humans using [99mTc]TRODAT-1 and single-photon emission tomography. Eur J Nucl Med 27:1714-8
Acton, P D; Kushner, S A; Kung, M P et al. (1999) Simplified reference region model for the kinetic analysis of [99mTc]TRODAT-1 binding to dopamine transporters in nonhuman primates using single-photon emission tomography. Eur J Nucl Med 26:518-26
Dresel, S H; Kung, M P; Huang, X F et al. (1999) Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in baboons. J Nucl Med 40:660-6
Mu, M; Kung, M P; Plossl, K et al. (1999) A simplified method to determine [99mTc]TRODAT-1 in human plasma. Nucl Med Biol 26:821-5
Mozley, P D; Acton, P D; Barraclough, E D et al. (1999) Effects of age on dopamine transporters in healthy humans. J Nucl Med 40:1812-7
Choi, S R; Kung, M P; Plossl, K et al. (1999) An improved kit formulation of a dopamine transporter imaging agent: [Tc-99m]TRODAT-1. Nucl Med Biol 26:461-6

Showing the most recent 10 out of 66 publications