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Titolo:
Reporter gene imaging: Effects of ganciclovir treatment on nucleoside uptake, hypoxia and perfusion in a murine gene therapy tumour model that expresses herpes simplex type-1 thymidine kinase
Autore:
Morin, KW; Knaus, EE; Wiebe, LI; Xia, H; McEwan, AJB;
Indirizzi:
Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada Univ Alberta Edmonton AB Canada T6G 2N8 Sci, Edmonton, AB T6G 2N8, Canada
Titolo Testata:
NUCLEAR MEDICINE COMMUNICATIONS
fascicolo: 2, volume: 21, anno: 2000,
pagine: 129 - 137
SICI:
0143-3636(200002)21:2<129:RGIEOG>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPERIMENTAL BRAIN-TUMORS; IN-VIVO; HUMAN-CELLS; CYTOKINES; TRANSDUCTION; REGRESSION; GLYCOLYSIS; PROTEINS; INVITRO; VECTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Wiebe, LI Univ Alberta, Noujaim Inst Pharmaceut Oncol Res, 3118 Dent PharmBldg, Edmonton, AB T6G 2N8, Canada Univ Alberta 3118 Dent Pharm Bldg Edmonton AB Canada T6G 2N8 ada
Citazione:
K.W. Morin et al., "Reporter gene imaging: Effects of ganciclovir treatment on nucleoside uptake, hypoxia and perfusion in a murine gene therapy tumour model that expresses herpes simplex type-1 thymidine kinase", NUCL MED C, 21(2), 2000, pp. 129-137

Abstract

Perfusion, hypoxia and nucleoside uptake during ganciclovir therapy were determined in a murine HSV-1 TK-expressing tumour model (KBALB-STK). HSV-1 TK mRNA transcription in this cell Line was confirmed by RT-PCR. BALB/c micebearing KBALB-STK tumours accumulated (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyuridine ([I-125]IVFRU) (2.54% injected dose.g(-1)) and could be readily detected with planar imaging following administration of [I-131]IVFRU. However, a single dose of ganciclovir (100 mg.kg(-1) intraperitoneally) decreased tumour uptake of [I-125]IVFRU to 0.33% injected dose.g(-1). Subsequent single daily doses of ganciclovir over 3 consecutive days had a negligible effect on [I-125]IVFRU uptake, which remained low. Tumour perfusion during 3 days of ganciclovir treatment was monitored with intravenous [Tc-99(m)]HMPAO. Tumour perfusion increased from day 0 (no ganciclovir treatment) with 1.83% injected dose.g(-1) tumour, to a maximum at day 2 (3.77% injected dose.g(-1)). In the same animals, accumulation of [H-3]misonidazole decreased from 0.70% injected dose.g(-1) at day 0 to a minimum at day 3 (0.24% injected dose.g(-1)), indicating that tumour tissue had become less hypoxic over the ganciclovir regimen. The uptake of [I-125]IVFRU into the acid insoluble fraction of KBALB-STK cells in vitro in the presence of ganciclovir (2.0 mu M) was completely inhibited, leading to a 57% decrease in total cellular accumulation of radioactivity. However, cytosolic entrapment of [I-125]IVFRU was not affected by the presence of ganciclovir. These results indicate that the mechanisms leading to IVFRU exclusion during ganciclovir treatment of HSV-1 TK-expressing tumours can be attributed, at least partially, to inhibition of [I-125]IVFRU-nucleotide incorporation into DNA. (C) 2000 Lippincott Williams & Wilkins).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 01:33:39