title: In vivo magnetic resonance imaging of mice liver tumors using a new gadolinium-based contrast agent.
abstract: We compared the enhancement effect between a newly synthesized tissue-specific contrast agent, [Gd-DOTA-FPβG], and a commercially available agent, [Gd(DOTA)](-), in a murine model of liver tumor using a clinical magnetic resonance imaging scanner. The colon cancer cell lines with and without β-glucuronidase (βG) expression were implanted into the liver of mice. Self-synthesized gadolinium-based magnetic resonance contrast agent, [Gd(DOTA-FPβG)], was administered to measure enhancement on magnetic resonance images using a commercially available agent, [Gd(DOTA)](-), as control in a clinical 3.0 tesla (T) magnetic resonance scanner. In vivo fluorescence imaging and histopathology of the liver were also performed to compare and correlate with the magnetic resonance studies. The in vivo fluorescence imaging failed to depict a sufficiently intense signal for liver or liver tumor of mice without exposure of the liver following an incision on the abdominal wall. The tissue-specific magnetic resonance agent, [Gd(DOTA-FPβG)], caused significantly stronger enhancement in tumors expressing βG (CT26/mβG-eB7) than in tumors not expressing βG (CT26) (p < 0.05). In the magnetic resonance imaging studies using control agent [Gd(DOTA)](-), the tumors with and without βG expression depicted no significant difference in enhancement on the T1-weighted images. The [Gd(DOTA-FPβG)] also provided significantly more contrast uptake in the CT26/mβG-eB7 tumor than in the normal liver parenchyma, whereas the [Gd(DOTA)](-) did not. This study confirms that better contrast enhancement can be readily detected in vivo by the use of a tissue-specific magnetic resonance contrast agent to target tumor cells with specific biomarkers in a clinical magnetic resonance imaging scanner.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Shih-Hsien
authors: SH
authors: Chen
authors: Yu-Ting
authors: YT
authors: Kuo
authors: Tian-Lu
authors: TL
authors: Cheng
authors: Chiao-Yun
authors: CY
authors: Chen
authors: Yen-Yu
authors: YY
authors: Chiu
authors: Jui-Jen
authors: JJ
authors: Lai
authors: Chih-Ching
authors: CC
authors: Chang
authors: Twei-Shiun
authors: TS
authors: Jaw
authors: Yun-Ming
authors: YM
authors: Wang
authors: Gin-Chung
authors: GC
authors: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000493:pharmacokinetics; D005965:Glucuronates / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D009942:Organometallic Compounds / Q000493:pharmacokinetics
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D005965:Glucuronates; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C584494:gadolinium-1-(2-difluoromethyl-4-(1-(4,7,10-triscarboxymethyl(1,4,7,10-tetraazacyclodecyl))acetamido)phenyl)glucopyronuronate; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
references: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1206-11
references: 10655509
references: Adv Cancer Res. 1993;60:269-91
references: 8417501
references: Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):824-31
references: 18755560
references: Gene Ther. 2007 Apr;14(7):565-74
references: 17235292
references: J Magn Reson Imaging. 2010 May;31(5):1106-16
references: 20432345
references: Patol Pol. 1978 Apr-Jun;29(2):143-51
references: 704178
references: Clin Gastroenterol Hepatol. 2011 Feb;9(2):161-7
references: 20920597
references: Am J Gastroenterol. 2006 Mar;101(3):513-23
references: 16542288
references: J Magn Reson Imaging. 2010 Oct;32(4):903-13
references: 20882621
references: Obstet Gynecol. 2011 Aug;118(2 Pt 1):280-288
references: 21775843
references: J Magn Reson Imaging. 2010 Aug;32(2):360-6
references: 20677263
references: Nat Biotechnol. 1997 Oct;15(10):961-4
references: 9335045
references: J Magn Reson Imaging. 2008 Jun;27(6):1322-6
references: 18504744
references: Bioconjug Chem. 2007 Nov-Dec;18(6):1716-27
references: 17935289
references: J Magn Reson Imaging. 2008 Aug;28(2):390-5
references: 18666145
references: Gene Ther. 2000 Aug;7(15):1333-6
references: 10918505
references: J Hepatol. 2012 Jun;56(6):1384-91
references: 22326465
references: J Magn Reson Imaging. 2010 Jul;32(1):229-34
references: 20578029
references: Oncogene. 2010 Sep 9;29(36):4989-5005
references: 20639898
references: J Magn Reson Imaging. 2004 Nov;20(5):826-37
references: 15503325
references: Bioorg Med Chem. 2006 Jan 15;14(2):326-33
references: 16185878
references: J Magn Reson Imaging. 2009 Oct;30(4):849-54
references: 19787734
references: J Magn Reson Imaging. 2011 Jul;34(1):69-78
references: 21598343
references: J Magn Reson Imaging. 1999 May;9(5):704-10
references: 10331767
references: Hum Gene Ther. 2011 Dec;22(12):1563-74
references: 21851208
references: Bioconjug Chem. 2010 May 19;21(5):911-20
references: 20415436
references: J Magn Reson Imaging. 2010 Feb;31(2):373-82
references: 20099351
references: Invest Radiol. 2011 Jul;46(7):441-9
references: 21512397
references: Gene Ther. 2002 Dec;9(24):1659-66
references: 12457279
references: J Magn Reson Imaging. 1993 Jan-Feb;3(1):41-9
references: 8428100
references: J Magn Reson Imaging. 2004 Oct;20(4):632-9
references: 15390149
references: Curr Pharm Des. 2002;8(15):1391-403
references: 12052215
references: Arch Pathol Lab Med. 2011 Dec;135(12):1570-5
references: 22129186
references: J Magn Reson Imaging. 2010 Sep;32(3):719-25
references: 20815073
references: AJR Am J Roentgenol. 2012 Jan;198(1):106-14
references: 22194485