Our objective is the development of an improved, noninvasive technique for early detection of metastases. This proposal is focused on carcinoma of the prostate and is based on two recent developments: (a) the realization that polyamine uptake by the prostate is enhanced many-fold by pretreatment with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) and (b) the rapid development of positron-emission transaxial tomography (PETT) scanning. In the course of this research project, we will determine the conditions for optimal uptake of polyamines by prostate derived tumors in animals. We will develop positron-emitting polyamine analogs and use them to scan tumor bearing animals. We shall subsequently conduct animal toxicity, clearance and dosimetry studies with the radiolabelled polyamines prior to using them for clinical studies. When the animal studies are completed and provided that approval is granted by the appropriate human studies committees, clinical studies are planned to determine the sensitivity and specificity of this scan in patients with carcinoma of the prostate. Finally, if the technology of nuclear magnetic resonance (NMR) imaging expands in the future, to use nuclei other than protons, for imaging (i.e. 19F, 13C, 15N), properly labelled polyamines suggest themselves as """"""""NMR contrast agents"""""""" in a similar fashion to their proposed use with the PETT scanner. Appropriate studies to investigate such a possibility will then be conducted.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA000931-02
Application #
3071525
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1984-04-15
Project End
1989-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
Latham, K M; Eastman, S W; Wong, A et al. (1996) Inhibition of p53-mediated growth arrest by overexpression of cyclin-dependent kinases. Mol Cell Biol 16:4445-55
Heston, W D; Kadmon, D (1986) alpha-Difluoromethylornithine enhancement of 14C-putrescine uptake by an androgen-dependent prostatic tumor. J Urol 136:944-8
Hwang, D R; Jerabek, P A; Kadmon, D et al. (1986) 2-[18F]fluoroputrescine: preparation, biodistribution, and mechanism of defluorination. Int J Rad Appl Instrum A 37:607-12
Kadmon, D; Ling, D; Lee, J K (1986) Percutaneous drainage of prostatic abscesses. J Urol 135:1259-60
Jerabek, P A; Dence, C S; Kilbourn, M R et al. (1985) Synthesis and uptake of no-carrier-added 1-[11C]putrescine into rat prostate. Int J Nucl Med Biol 12:349-52
Kadmon, D; Mahle, C; Heston, W D et al. (1985) Effect of estrogen and androgen administration on alpha-difluoromethylornithine-enhanced putrescine uptake by the rat prostate. Prostate 6:343-9