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Titolo:
Biodistribution and metabolism of a mixed backbone oligonucleotide (GEM 231) following single and multiple dose administration in mice
Autore:
Rusckowski, M; Qu, T; Roskey, A; Agrawal, S;
Indirizzi:
Hybridon Inc, Cambridge, MA 02139 USA Hybridon Inc Cambridge MA USA 02139Hybridon Inc, Cambridge, MA 02139 USA Univ Massachusetts, Sch Med, Dept Radiol, Div Nucl Med, Worcester, MA 01655 USA Univ Massachusetts Worcester MA USA 01655 cl Med, Worcester, MA 01655 USA
Titolo Testata:
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
fascicolo: 5, volume: 10, anno: 2000,
pagine: 333 - 345
SICI:
1087-2906(200010)10:5<333:BAMOAM>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE GEM-91; IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VIVO STABILITY; PROTEIN-KINASE-A; ANTISENSE OLIGONUCLEOTIDE; TISSUE DISTRIBUTION; PHARMACOKINETIC PROPERTIES; CGP 69846A; RATS; DISPOSITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Agrawal, S Hybridon Inc, 345 Vassar St, Cambridge, MA 02139 USA Hybridon Inc 345 Vassar St Cambridge MA USA 02139 MA 02139 USA
Citazione:
M. Rusckowski et al., "Biodistribution and metabolism of a mixed backbone oligonucleotide (GEM 231) following single and multiple dose administration in mice", ANTISENSE N, 10(5), 2000, pp. 333-345

Abstract

Biodistribution and metabolism of a mixed backbone oligonucleotide (MBO), GEM 231, targeted to the RI alpha subunit of protein kinase A has been studied in normal and tumor xenografted mice. The study has been carried out using [S-35]-labeled MBO following single and multiple administrations of doses varying from 2 to 50 mg/kg. MBO showed wide tissue distribution following intravenous and subcutaneous administration. The highest concentration ofMBO was in the kidney and liver. The general disposition of MBO was followed by digitized autoradiographic pictures of tumored mice and further confirmed wide tissue disposition and also showed defined intratumor uptake of MBO. Multiple dose administration showed increased disposition in the majority of the tissues/organs, with the exception of the kidneys. Analysis of the extracted MBO by polyacrylamide gel electrophoresis (PAGE) showed the presence of primarily intact MBO along with its degraded forms. Based on our radioactivity levels, the primary route of excretion was in urine, analysis of which showed mainly degraded forms of MBO.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 12:34:41