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Titolo:
PRECLINICAL ASSESSMENT OF HYPOXIC MARKER SPECIFICITY AND SENSITIVITY
Autore:
IYER RV; ENGELHARDT EL; STOBBE CC; SCHNEIDER RF; CHAPMAN JD;
Indirizzi:
FOX CHASE CANC CTR,DEPT RADIAT ONCOL,TUMOR BIOL & BIOPHYS SECT,7701 BURHOLME AVE PHILADELPHIA PA 19111 FOX CHASE CANC CTR,DEPT RADIAT ONCOL,TUMOR BIOL & BIOPHYS SECT PHILADELPHIA PA 19111
Titolo Testata:
International journal of radiation oncology, biology, physics
fascicolo: 4, volume: 42, anno: 1998,
pagine: 741 - 745
SICI:
0360-3016(1998)42:4<741:PAOHMS>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR HYPOXIA; OXYGENATION PREDICTS; PHOTODYNAMIC THERAPY; MISONIDAZOLE BINDING; ADVANCED CANCER; UTERINE CERVIX; TISSUE HYPOXIA; MURINE TUMORS; MOUSE-TUMORS; SOLID TUMORS;
Keywords:
HYPOXIC MARKER; AZOMYCIN NUCLEOSIDE; TECHNETIUM CHELATE; HYPOXIC-SPECIFIC FACTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
R.V. Iyer et al., "PRECLINICAL ASSESSMENT OF HYPOXIC MARKER SPECIFICITY AND SENSITIVITY", International journal of radiation oncology, biology, physics, 42(4), 1998, pp. 741-745

Abstract

Purpose: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. Materials and Methods: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumorsin vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor inthis host exhibited an average radiobiologic HF of similar to 35%. Aswell, nuclear medicine images were acquired from R3327-AT (HF = 15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. Results: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well-perfused R3327-H tumors. While both FC-306 and CERETEC(R) rapidly distributed at unique concentrations to different tissues, their avidity to EMT-6 and R3327-AT tumors did not correlate with tumor HF. Conclusions: The halogenated azomycinnucleosides with the lowest lipid/water partition coefficient values were found to yield the optimal hypoxia-specific signal in these animal tumors. Our Tc-99m-labeled azomycin chelates showed little or no hypoxia-specific uptake and had in vivo biodistribution and clearance kinetics similar to those of CERETEC(R), a perfusion agent with no known hypoxic binding activity. (C) 1998 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 06:44:26