title: Fluorescence lifetime imaging system for in vivo studies.
abstract: In this article, a fluorescence lifetime imaging system for small animals is presented. Data were collected by scanning a region of interest with a measurement head, a linear fiber array with fixed separations between a single source fiber and several detection fibers. The goal was to localize tumors and monitor their progression using specific fluorescent markers. We chose a near-infrared contrast agent, Alexa Fluor 750 (Invitrogen Corp., Carlsbad, CA). Preliminary results show that the fluorescence lifetime for this dye was sensitive to the immediate environment of the fluorophore (in particular, pH), making it a promising candidate for reporting physiologic changes around a fluorophore. To quantify the intrinsic lifetime of deeply embedded fluorophores, we performed phantom experiments to investigate the contribution of photon migration effects on observed lifetime by calculating the fluorescence intensity decay time. A previously proposed theoretical model of migration, based on random walk theory, is also substantiated by new experimental data. The developed experimental system has been used for in vivo mouse imaging with Alexa Fluor 750 contrast agent conjugated to tumor-specific antibodies (trastuzumab [Herceptin]). Three-dimensional mapping of the fluorescence lifetime indicates lower lifetime values in superficial breast cancer tumors in mice.
authors: Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD 20892, USA. hassanm@mail.nih.gov
authors: Moinuddin
authors: M
authors: Hassan
authors: Jason
authors: J
authors: Riley
authors: Victor
authors: V
authors: Chernomordik
authors: Paul
authors: P
authors: Smith
authors: Randall
authors: R
authors: Pursley
authors: Sang Bong
authors: SB
authors: Lee
authors: Jacek
authors: J
authors: Capala
authors: Amir H
authors: AH
authors: Gandjbakhche
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D004952:Esters / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019047:Phantoms, Imaging; D012117:Resins, Synthetic / Q000378:metabolism; D013388:Succinimides; D013997:Time Factors; D000068878:Trastuzumab
chemical_list: C502599:Alexa Fluor 750; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004952:Esters; D005456:Fluorescent Dyes; D012117:Resins, Synthetic; D013388:Succinimides; C010102:delrin; D000068878:Trastuzumab
references: J Opt Soc Am A Opt Image Sci Vis. 2001 Jul;18(7):1523-30
references: 11444544
references: J Fluoresc. 2004 Sep;14(5):561-8
references: 15617263
references: Opt Lett. 2004 Mar 15;29(6):584-6
references: 15035478
references: Proc Natl Acad Sci U S A. 1982 Mar;79(6):2128-32
references: 16593174
references: Cancer Res. 1989 Dec 1;49(23):6449-65
references: 2684393
references: Lasers Surg Med. 2004;35(5):342-8
references: 15611954
references: Med Phys. 2005 Apr;32(4):992-1000
references: 15895582
references: Cytometry A. 2006 Apr;69(4):299-306
references: 16498675
references: J Biomed Opt. 2005 Sep-Oct;10(5):054003
references: 16292963
references: Clin Transl Oncol. 2006 Feb;8(2):77-82
references: 16632420
references: Oncogene. 2003 Sep 29;22(42):6570-8
references: 14528282
references: Clin Cancer Res. 2003 Mar;9(3):923-30
references: 12631589
references: Int J Clin Oncol. 2006 Jun;11(3):199-208
references: 16850126
references: Opt Lett. 2004 Oct 1;29(19):2258-60
references: 15524373
references: Anal Biochem. 1992 May 1;202(2):316-30
references: 1519759
references: Exp Cell Res. 2005 Oct 1;309(2):390-6
references: 16040027
references: Phys Med Biol. 2002 Sep 21;47(18):3387-405
references: 12375827
references: Br J Cancer. 1991 Sep;64(3):425-7
references: 1911181
references: Opt Lett. 2005 Dec 15;30(24):3347-9
references: 16389827