Abstract

Radiolabelling of BCNU by C-11 or N-13 has provided a means of mapping, with PET sequential scans, the entry, distribution, and persistence of this drug in Grade III and IV human gliomas. Our preliminary findings indicate that the differential uptake of the drug is greater in the tumor than in a control area of brain, and that it also has a different clearance half-life. PET mapping following supra-selective intracerebral arterial infusion of BCNU has shown significant reduction, and in one case almost total disappearance of the tumor. More detailed studies using PET and experimental radioautography of radio-labelled BCNU, AspCNU, and SarCNU will be made. The resulting information would improve the scientific basis and methodology of administration of drugs now available. It would also provide a model for evaluating new drugs. The metabolic information derived from PET scanning of gliomas would help to correlate these chemical and biological activity and provide a means of early detection of tumor response to chemotherapy and radiotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS022230-03S1
Application #
3404411
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-01-01
Project End
1989-02-28
Budget Start
1989-01-01
Budget End
1989-02-28
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Mcgill University
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 2T5

  Publications

Chen, Z P; Yarosh, D; Garcia, Y et al. (1999) Relationship between O6-methylguanine-DNA methyltransferase levels and clinical response induced by chloroethylnitrosourea therapy in glioma patients. Can J Neurol Sci 26:104-9
Chen, Z P; McQuillan, A; Mohr, G et al. (1998) Excision repair cross-complementing rodent repair deficiency gene 2 expression and chloroethylnitrosourea resistance in human glioma cell lines. Neurosurgery 42:1112-9
Chen, Z P; Malapetsa, A; Mohr, G et al. (1997) Quantitation of ERCC-2 gene expression in human tumor cell lines by reverse transcription-polymerase chain reaction in comparison to northern blot analysis. Anal Biochem 244:50-4
Chen, Z P; Malapetsa, A; McQuillan, A et al. (1997) Evidence for nucleotide excision repair as a modifying factor of O6-methylguanine-DNA methyltransferase-mediated innate chloroethylnitrosourea resistance in human tumor cell lines. Mol Pharmacol 52:815-20
Panasci, L C; Marcantonio, D; Noe, A J (1996) SarCNU (2-chloroethyl-3-sarcosinamide-1-nitrosourea): a novel analogue of chloroethylnitrosourea that is transported by the catecholamine uptake2 carrier, which mediates increased cytotoxicity. Cancer Chemother Pharmacol 37:505-8
Noe, A J; Marcantonio, D; Barton, J et al. (1996) Characterization of the catecholamine extraneuronal uptake2 carrier in human glioma cell lines SK-MG-1 and SKI-1 in relation to (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) selective cytotoxicity. Biochem Pharmacol 51:1639-48
Malapetsa, A; Noe, A J; Poirier, G G et al. (1996) Identification of a 116 kDa protein able to bind 1,3-bis(2-chloroethyl)-1-nitrosourea-damaged DNA as poly(ADP-ribose) polymerase. Mutat Res 362:41-50
Chen, Z P; Malapetsa, A; Marcantonio, D et al. (1996) Correlation of chloroethylnitrosourea resistance with ERCC-2 expression in human tumor cell lines as determined by quantitative competitive polymerase chain reaction. Cancer Res 56:2475-8
Bramson, J; O'Connor, T; Panasci, L (1995) Effect of alkyl-N-purine DNA glycosylase overexpression on cellular resistance to bifunctional alkylating agents. Biochem Pharmacol 50:39-44
Noe, A J; Malapetsa, A; Panasci, L C (1994) Altered cytotoxicity of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea in human glioma cell lines SK-MG-1 and SKI-1 correlates with differential transport kinetics. Cancer Res 54:1491-6

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