The formation of cancer is normally accompanied by changes in metabolic features of neoplastic tissue when compared with normal tissue. During the last few years we capitalized in this conceptand developed the necessay expertise to synthesize and test a group of metabolic tracers, amino acids, sugars and their analogs as specific agents for visualization of tumors. Our results with positron labeled sugars and (N-13) amino acids indicate that this approach is useful. The main objective of this research proposal is to continue the development of radiopharmacueticals bearing positron radionuclides for imaging and quantitation of organs containing neoplastic diseases. The emphasis, however, will be on agents with known specific metabolic agents processes. The behavior of these radiolabeled specific agents will be evaluated in tumor tissues for their rate of tissue uptake and clearance to determine the functional status and morphology of neoplastic tissue prior to, during and after radiotherapy treatment. The radiopharmaceuticals of choice are D and L (F-18)fluoro amino acids of methionine and leucine and their D and L Alpha-methyl derivatives. The transport and incorporation of these new amino acids into proteins will be studied in the animal tumor model. (F-18)DOPA will be prepared to study the selective incorporation of this melanin precursor into melanotic cells and melanoma deposits. Diadenosine 5',5'''-p1,p4-tetraphoshate was found to be incorporated into well identified human malignant cells. Its (C-11) label will be prepared and studied in specific cell cultures and tumor cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026371-07
Application #
3167277
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1979-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Niles, Jacquin C; Wishnok, John S; Tannenbaum, Steven R (2004) Mass spectrometric identification of 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid during oxidation of 8-oxoguanosine by peroxynitrite and KHSO5/CoCl2. Chem Res Toxicol 17:1501-9
Niles, Jacquin C; Wishnok, John S; Tannenbaum, Steven R (2004) Spiroiminodihydantoin and guanidinohydantoin are the dominant products of 8-oxoguanosine oxidation at low fluxes of peroxynitrite: mechanistic studies with 18O. Chem Res Toxicol 17:1510-9
Spek, Erik J; Vuong, Laurel N; Matsuguchi, Tetsuya et al. (2002) Nitric oxide-induced homologous recombination in Escherichia coli is promoted by DNA glycosylases. J Bacteriol 184:3501-7
Spek, E J; Wright, T L; Stitt, M S et al. (2001) Recombinational repair is critical for survival of Escherichia coli exposed to nitric oxide. J Bacteriol 183:131-8
Niles, J C; Wishnok, J S; Tannenbaum, S R (2001) Spiroiminodihydantoin is the major product of the 8-oxo-7,8-dihydroguanosine reaction with peroxynitrite in the presence of thiols and guanosine photooxidation by methylene blue. Org Lett 3:963-6
Kizuka, H; Elmaleh, D R; Boudreaux, G J et al. (1986) N-[11C-Methyl]chlorphentermine and N,N-[11C-dimethyl]chlorphentermine as brain blood-flow agents for positron emission tomography. J Nucl Med 27:532-7
Kairento, A L; Brownell, G L; Elmaleh, D R et al. (1985) Comparative measurement of regional blood flow, oxygen and glucose utilisation in soft tissue tumour of rabbit with positron imaging. Br J Radiol 58:637-43