PURPOSE: To determine the feasibility of T2-weighted magnetic resonance (MR) imaging in the noninvasive quantification of renal inflammation by using superparamagnetic iron oxide (SPIO) nanoparticles targeted to tissue-bound C3 activation fragments in a mouse model of lupus nephritis. MATERIALS AND METHODS: All animal procedures were approved by the University of Colorado-Denver animal care and use committee. SPIO nanoparticles were encapsulated by using amine-functionalized phospholipids. A recombinant protein containing the C3d-binding region of complement receptor type 2 (CR2) was then conjugated to the surface of the SPIO nanoparticle. Five MRL/lpr mice (a model of lupus nephritis) and six C57BL/6 wild-type mice were assessed with T2-weighted MR imaging at baseline and after SPIO injection. The same five MRL/lpr mice and three C57BL/6 mice also underwent MR imaging after injection of CR2-targeted SPIO. A series of T2-weighted pulses with 16 echo times was used to enable precise T2 mapping and calculation of T2 relaxation times in the cortex and outer and inner medulla of the kidneys, as well as in the spleen, muscle, and fat. The effects of treatment and animal genotype on T2 relaxation times were analyzed with repeated-measures analysis of variance. RESULTS: At baseline, the T2-weighted signal intensity in the kidneys of MRL/lpr mice was higher than that in the kidneys of wild-type mice. Injection of untargeted SPIO did not alter the T2-weighted signal in the kidneys in either strain of mice. Injection of CR2-targeted SPIO in MRL/lpr mice, however, caused a significant accumulation of targeted iron oxide with a subsequent decrease in T2 relaxation times in the cortex and outer and inner medulla of the kidneys. No changes in T2 relaxation time were observed in the wild-type mice after injection of targeted SPIO. CONCLUSION: Injection of CR2-conjugated SPIO caused a significant reduction in T2-weighted MR imaging signal and T2 relaxation time in nephritic kidneys.
PURPOSE: To determine the feasibility of T2-weighted magnetic resonance (MR) imaging in the noninvasive quantification of renal inflammation by using superparamagnetic iron oxide (SPIO) nanoparticles targeted to tissue-bound C3 activation fragments in a mouse model of lupus nephritis. MATERIALS AND METHODS: All animal procedures were approved by the University of Colorado-Denver animal care and use committee. SPIO nanoparticles were encapsulated by using amine-functionalized phospholipids. A recombinant protein containing the C3d-binding region of complement receptor type 2 (CR2) was then conjugated to the surface of the SPIO nanoparticle. Five MRL/lpr mice (a model of lupus nephritis) and six C57BL/6 wild-type mice were assessed with T2-weighted MR imaging at baseline and after SPIO injection. The same five MRL/lpr mice and three C57BL/6 mice also underwent MR imaging after injection of CR2-targeted SPIO. A series of T2-weighted pulses with 16 echo times was used to enable precise T2 mapping and calculation of T2 relaxation times in the cortex and outer and inner medulla of the kidneys, as well as in the spleen, muscle, and fat. The effects of treatment and animal genotype on T2 relaxation times were analyzed with repeated-measures analysis of variance. RESULTS: At baseline, the T2-weighted signal intensity in the kidneys of MRL/lpr mice was higher than that in the kidneys of wild-type mice. Injection of untargeted SPIO did not alter the T2-weighted signal in the kidneys in either strain of mice. Injection of CR2-targeted SPIO in MRL/lpr mice, however, caused a significant accumulation of targeted iron oxide with a subsequent decrease in T2 relaxation times in the cortex and outer and inner medulla of the kidneys. No changes in T2 relaxation time were observed in the wild-type mice after injection of targeted SPIO. CONCLUSION: Injection of CR2-conjugated SPIO caused a significant reduction in T2-weighted MR imaging signal and T2 relaxation time in nephritic kidneys.
Authors: J W Bulte; T Douglas; B Witwer; S C Zhang; E Strable; B K Lewis; H Zywicke; B Miller; P van Gelderen; B M Moskowitz; I D Duncan; J A Frank Journal: Nat Biotechnol Date: 2001-12 Impact factor: 54.908
Authors: Siranush A Sargsyan; Natalie J Serkova; Brandon Renner; Kendra M Hasebroock; Brian Larsen; Conrad Stoldt; Kim McFann; Matthew C Pickering; Joshua M Thurman Journal: Kidney Int Date: 2011-09-28 Impact factor: 10.612
Authors: Cartney E Smith; Dawn Ernenwein; Artem Shkumatov; Nicholas E Clay; JuYeon Lee; Molly Melhem; Sanjay Misra; Steven C Zimmerman; Hyunjoon Kong Journal: Biomaterials Date: 2015-08-04 Impact factor: 12.479
Authors: Michael Look; Eric Stern; Qin A Wang; Leah D DiPlacido; Michael Kashgarian; Joe Craft; Tarek M Fahmy Journal: J Clin Invest Date: 2013-04 Impact factor: 14.808
Authors: Joshua M Thurman; Liudmila Kulik; Heather Orth; Maria Wong; Brandon Renner; Siranush A Sargsyan; Lynne M Mitchell; Dennis E Hourcade; Jonathan P Hannan; James M Kovacs; Beth Coughlin; Alex S Woodell; Matthew C Pickering; Bärbel Rohrer; V Michael Holers Journal: J Clin Invest Date: 2013-04-24 Impact factor: 14.808