title: Physiologically based pharmacokinetics of molecular imaging nanoparticles for mRNA detection determined in tumor-bearing mice.
abstract: Disease detection and management might benefit from external imaging of disease gene mRNAs. Previously we designed molecular imaging nanoparticles (MINs) based on peptide nucleic acids complementary to cancer gene mRNAs. The MINs included contrast agents and analogs of insulin-like growth factor 1 (IGF-1). Analysis of MIN tumor uptake data showed stronger binding in tumors than in surrounding tissues. We hypothesized that MINs with an IGF-1 analog stay in circulation by binding to IGF-binding proteins. To test that hypothesis, we fit the tissue distribution results of several MINs in xenograft-bearing mice to a physiological pharmacokinetics model. Fitting experimental tissue distribution data to model-predicted mass transfer of MINs from blood into organs and tumors converged only when the parameter for MINs bound to circulating IGF-binding proteins was set to 10%-20% of the injected MIN dose. This result suggests that previous mouse imaging trials used more MINs than necessary. This prediction can be tested by a ramp of decreasing doses.
authors.affiliation: Department of Chemical Engineering, Center for Molecular and Engineering Thermodynamics, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Armin W
authors.initials: AW
authors.lastname: Opitz
authors.forename: Eric
authors.initials: E
authors.lastname: Wickstrom
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Thakur
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Wagner
mesh_terms: D000818:Animals; D051379:Mice; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000235:genetics*; D010599:Pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis*; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger
references.citation: Ann Emerg Med. 1986 Apr;15(4):390-6
references.pmid: 3954170
references.citation: J Nucl Med. 2007 Oct;48(10):1699-707
references.pmid: 17909257
references.citation: Ann Biomed Eng. 2006 Apr;34(4):618-32
references.pmid: 16547609
references.citation: Growth Horm IGF Res. 2003 Aug;13(4):113-70
references.pmid: 12914749
references.citation: Biotechnol Prog. 1999 May-Jun;15(3):540-55
references.pmid: 10356275
references.citation: J Pharm Sci. 1983 Oct;72(10):1103-27
references.pmid: 6358460
references.citation: Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):435-44
references.pmid: 14604834
references.citation: Eur J Cancer Clin Oncol. 1983 Jul;19(7):1021-9
references.pmid: 6684042
references.citation: MAGMA. 2004 Dec;17(3-6):157-61
references.pmid: 15609036
references.citation: J Pharmacokinet Pharmacodyn. 2003 Jun;30(3):185-219
references.pmid: 14571691
references.citation: Am J Physiol. 1996 Oct;271(4 Pt 1):E649-57
references.pmid: 8897852
references.citation: J Clin Invest. 1986 Dec;78(6):1504-12
references.pmid: 2431001
references.citation: J Nucl Med. 2004 Dec;45(12):2070-82
references.pmid: 15585484
references.citation: Biopolymers. 2008 Dec;89(12):1061-76
references.pmid: 18680101
references.citation: Ann N Y Acad Sci. 2003 Dec;1002:165-88
references.pmid: 14751834
references.citation: J Pharmacokinet Biopharm. 1994 Aug;22(4):259-92
references.pmid: 7699583
references.citation: J Appl Toxicol. 1983 Dec;3(6):310-2
references.pmid: 6677653
references.citation: Cancer Res. 1988 May 15;48(10):2641-58
references.pmid: 3282647
references.citation: Microvasc Res. 1993 May;45(3):269-89
references.pmid: 8321142
references.citation: Circ Res. 1956 Jul;4(4):419-24
references.pmid: 13330185
references.citation: Am J Physiol. 1997 Aug;273(2 Pt 1):E438-47
references.pmid: 9277399
references.citation: Proc Soc Exp Biol Med. 1950 Jul;74(3):644-8
references.pmid: 15440918
references.citation: J Cell Physiol. 1997 Mar;170(3):290-8
references.pmid: 9066786
references.citation: J Cell Physiol. 2007 Feb;210(2):298-308
references.pmid: 17044083
references.citation: Pharm Res. 2001 Aug;18(8):1203-9
references.pmid: 11587493
references.citation: Cancer. 1974 Jan;33(1):103-10
references.pmid: 4810083
references.citation: Ann N Y Acad Sci. 2005 Nov;1059:106-44
references.pmid: 16382049
references.citation: Am J Physiol. 1990 Mar;258(3 Pt 1):G365-9
references.pmid: 2316651
references.citation: Am J Physiol. 1992 Sep;263(3 Pt 2):R728-33
references.pmid: 1415664
references.citation: Gut. 2002 Apr;50(4):507-12
references.pmid: 11889071
references.citation: Lab Anim. 2002 Jan;36(1):1-19
references.pmid: 11833526
references.citation: Physiol Rev. 1990 Jul;70(3):591-614
references.pmid: 1694588
references.citation: Am J Physiol Gastrointest Liver Physiol. 2005 Jun;288(6):G1328-38
references.pmid: 15637179
references.citation: Curr Top Dev Biol. 2005;70:1-33
references.pmid: 16338335
references.citation: J Clin Endocrinol Metab. 1989 Mar;68(3):535-41
references.pmid: 2563734
references.citation: Lab Anim. 2002 Oct;36(4):411-9
references.pmid: 12396284
references.citation: J Pharmacokinet Biopharm. 1997 Jun;25(3):277-312
references.pmid: 9474530
references.citation: Proc R Soc Lond B Biol Sci. 1965 Jul 27;162(989):502-16
references.pmid: 4378461
references.citation: Lab Anim Sci. 1972 Oct;22(5):712-20
references.pmid: 4343328
references.citation: Bioconjug Chem. 2005 Jan-Feb;16(1):70-9
references.pmid: 15656577
references.citation: J Endocrinol. 1999 Sep;162(3):361-9
references.pmid: 10467227
references.citation: Methods Inf Med. 1994 Dec;33(5):514-21
references.pmid: 7869950
references.citation: Antisense Nucleic Acid Drug Dev. 2001 Feb;11(1):15-27
references.pmid: 11258618
references.citation: Cancer Res. 1989 Jul 15;49(14):3759-64
references.pmid: 2736517
references.citation: Toxicol Appl Pharmacol. 1990 Nov;106(2):295-310
references.pmid: 2256118
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035
references.citation: Cancer Res. 1994 Mar 15;54(6):1517-28
references.pmid: 8137258
references.citation: Cancer Biol Ther. 2007 Jun;6(6):948-56
references.pmid: 17611392
references.citation: J Pharm Sci. 2000 Jan;89(1):115-27
references.pmid: 10664544