Metabolism studies of unformulated internally [3h]-labeled short interfering RNAs in mice

Drug Metabolism and Disposition

Volumn 41, Issue 6, 2013, Pages 1211-1219

  Christensen, Jesper ^a   Litherland, Karine ^a   Faller, Thomas ^a   Van De Kerkhof, Esther ^a   Natt, François ^b   Hunziker, Jürg ^b   Krauser, Joel ^a   Swart, Piet ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b Biologics Center   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2' O METHYLURIDINE; DRUG METABOLITE; RADIOPHARMACEUTICAL AGENT; TRITIUM MULTIDRUG RESISTANCE PROTEIN 4 H3 SMALL INTERFERING RNA H 3; TRITIUM SJOEGREN SYNDROME ANTIGEN B H3 SMALL INTERFERING RNA H 3; UNCLASSIFIED DRUG; URIDINE;

ACCURACY; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DEGRADATION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG RETENTION; DRUG TISSUE LEVEL; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; LIQUID SCINTILLATION COUNTING; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MOLECULAR WEIGHT; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIATION DETECTION; RADIOCHROMATOGRAPHY; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; WHOLE BODY AUTORADIOGRAPHY;

ANIMALS; FEMALE; INJECTIONS, INTRAVENOUS; MALE; MICE; RNA, SMALL INTERFERING; TISSUE DISTRIBUTION; TRITIUM;

EID: 84878228850     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.050666     Document Type: Article

References (32)

1. Bartlett DW, Su H, Hildebrandt IJ, Weber WA, and Davis ME (2007) Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci USA 104:15549-15554.
2. Beale G, Hollins AJ, Benboubetra M, Sohail M, Fox SP, Benter I, and Akhtar S (2003) Gene silencing nucleic acids designed by scanning arrays: anti-EGFR activity of siRNA, ribozyme and DNA enzymes targeting a single hybridization-accessible region using the same delivery system. J Drug Target 11:449-456.
3. Bogdanov AA, Jr (2008) Merging molecular imaging and RNA interference: early experience in live animals. J Cell Biochem 104:1113-1123.
4. Braasch DA, Paroo Z, Constantinescu A, Ren G, Oz OK, Mason RP, and Corey DR (2004) Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorg Med Chem Lett 14:1139-1143.
5. Christensen J, Natt F, Hunziker J, Krauser J, and Swart P (2012) Tritium labeling of full-length small interfering RNAs. J Labelled Comp Radiopharm 55:189-196.
6. Davies B and Morris T (1993) Physiological parameters in laboratory animals and humans. Pharm Res 10:1093-1095.
7. De Wolf HK, Snel CJ, Verbaan FJ, Schiffelers RM, Hennink WE, and Storm G (2007) Effect of cationic carriers on the pharmacokinetics and tumor localization of nucleic acids after intravenous administration. Int J Pharm 331:167-175.
8. Evans EA, Sheppard HC, and Turner JC (1970) Validity of tritium tracers-stability of tritium atoms in purines, pyrimidines, nucleosides and nucleotides. J Labelled Compd 6:76-87.
9. Gao S, Dagnaes-Hansen F, Nielsen E J B, Wengel J, Besenbacher F, Howard KA, and Kjems J (2009) The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 17:1225-1233.
10. Hatanaka K, Asai T, Koide H, Kenjo E, Tsuzuku T, Harada N, Tsukada H, and Oku N (2010) Development of double-stranded siRNA labeling method using positron emitter and its in vivo trafficking analyzed by positron emission tomography. Bioconjug Chem 21:756-763.
11. Kang L, Wang RF, Yan P, Liu M, Zhang CL, Yu MM, Cui YG, and Xu XJ (2010) Noninvasive visualization of RNA delivery with 99mTc-radiolabeled small-interference RNA in tumor xenografts. J Nucl Med 51:978-986.
12. Khan A, Benboubetra M, Sayyed PZ, Ng KW, Fox S, Beck G, Benter IF, and Akhtar S (2004) Sustained polymeric delivery of gene silencing antisense ODNs, siRNA, DNAzymes and ribozymes: in vitro and in vivo studies. J Drug Target 12:393-404.
13. Malek A, Czubayko F, and Aigner A (2008) PEG grafting of polyethylenimine (PEI) exerts different effects on DNA transfection and siRNA-induced gene targeting efficacy. J Drug Target 16:124-139.
14. Malek A, Merkel O, Fink L, Czubayko F, Kissel T, and Aigner A (2009) In vivo pharmacokinetics, tissue distribution and underlying mechanisms of various PEI (-PEG)/siRNA complexes. Toxicol Appl Pharmacol 236:97-108.
15. Merkel OM, Librizzi D, Pfestroff A, Schurrat T, Béhé M, and Kissel T (2009a) In vivo SPECT and real-time gamma camera imaging of biodistribution and pharmacokinetics of siRNA delivery using an optimized radiolabeling and purification procedure. Bioconjug Chem 20:174-182.
16. Merkel OM, Librizzi D, Pfestroff A, Schurrat T, Buyens K, Sanders NN, De Smedt SC, Béhé M, and Kissel T (2009b) Stability of siRNA polyplexes from poly (ethylenimine) and poly (ethylenimine)-g-poly (ethylene glycol) under in vivo conditions: effects on pharmacokinetics and biodistribution measured by Fluorescence Fluctuation Spectroscopy and Single Photon Emission Computed Tomography (SPECT) imaging. J Control Release 138:148-159.
17. Mook OR, Baas F, De Wissel MB, and Fluiter K (2007) Evaluation of locked nucleic acidmodified small interfering RNA in vitro and in vivo. Mol Cancer Ther 6:833-843.
18. Mook O R F, Vreijling J, Wengel SL, Wengel J, Zhou C, Chattopadhyaya J, Baas F, and Fluiter K (2010) In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts. Artif DNA PNA XNA 1:36-44.
19. Moore A and Medarova Z (2009) Imaging of siRNA Delivery and Silencing, in Methods in Molecular Biology, siRNA and miRNA Gene Silencing (Sioud M, ed) pp 93-110, Humana Press, New York.
20. Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S, and Jadhav V, et al. (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23:1002-1007.
21. Mudd SR, Trubetskoy VS, Blokhin AV, Weichert JP, and Wolff JA (2010) Hybrid PET/CT for noninvasive pharmacokinetic evaluation of dynamic PolyConjugates, a synthetic siRNA delivery system. Bioconjug Chem 21:1183-1189.
22. Noll S and Mittag E (1983) Investigation of hydrogen-exchange in uracil and its derivatives labeled with tritium. Reaction Kinetics and Catalysis Letters 22:35-37.
23. Ocker M, Neureiter D, Lueders M, Zopf S, Ganslmayer M, Hahn EG, Herold C, and Schuppan D (2005) Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer. Gut 54:1298-1308.
24. Richmond CR, Langham WH, and Trujillo TT (1962) Comparative metabolism of tritiated water by mammals. J Cell Comp Physiol 59:45-53.
25. Sands H, Gorey-Feret LJ, Cocuzza AJ, Hobbs FW, Chidester D, and Trainor GL (1994) Biodistribution and metabolism of internally 3H-labeled oligonucleotides. I. Comparison of a phosphodiester and a phosphorothioate. Mol Pharmacol 45:932-943.
26. Sands H, Gorey-Feret LJ, Ho SP, Bao YJ, Cocuzza AJ, Chidester D, and Hobbs FW (1995) Biodistribution and metabolism of internally 3H-labeled oligonucleotides. II. 39, 59-blocked oligonucleotides. Mol Pharmacol 47:636-646.
27. Sonoke S, Ueda T, Fujiwara K, Sato Y, Takagaki K, Hirabayashi K, Ohgi T, and Yano J (2008) Tumor regression in mice by delivery of Bcl-2 small interfering RNA with pegylated cationic liposomes. Cancer Res 68:8843-8851.
28. Swart PJ, Beljaars E, Smit C, Pasma A, Schuitemaker H, and Meijer D K F (1996) Comparative pharmacokinetic, immunologic and hematologic studies on the anti-HIV-1/2 compounds aconitylated and succinylated HSA. J Drug Target 4:109-116.
29. Van De Water FM, Boerman OC, Wouterse AC, Peters J G P, Russel F G M, and Masereeuw R (2006) Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules. Drug Metab Dispos 34:1393-1397.
30. Viel T, Boisgard R, Kuhnast B, Jego B, Siquier-Pernet K, Hinnen F, Dollé F, and Tavitian B (2008) Molecular imaging study on in vivo distribution and pharmacokinetics of modified small interfering RNAs (siRNAs). Oligonucleotides 18:201-212.
31. Yanagihara K, Tashiro M, Fukuda Y, Ohno H, Higashiyama Y, Miyazaki Y, Hirakata Y, Tomono K, Mizuta Y, and Tsukamoto K, et al. (2006) Effects of short interfering RNA against methicillin-resistant Staphylococcus aureus coagulase in vitro and in vivo. J Antimicrob Chemother 57:122-126.
32. Zou Y, Tiller P, Chen IW, Beverly M, and Hochman J (2008) Metabolite identification of small interfering RNA duplex by high-resolution accurate mass spectrometry. Rapid Commun Mass Spectrom 22:1871-1881.