PD32-06 ASSESSMENT OF PHARMACOLOGIC INTERVENTION ON CYSTINE STONE GROWTH USING IN VIVO IMAGING IN A MOUSE MODEL OF CYSTINURIA

Abstract

You have accessJournal of UrologyStone Disease: Evaluation II1 Apr 2014PD32-06 ASSESSMENT OF PHARMACOLOGIC INTERVENTION ON CYSTINE STONE GROWTH USING IN VIVO IMAGING IN A MOUSE MODEL OF CYSTINURIA Jaspreet Parihar, Kathleen Capaccione, Min Yang, Derek Adler, Derek Gordon, Joseph Barone, David Goldfarb, Jay Tischfield, and Amrik Sahota Jaspreet PariharJaspreet Parihar More articles by this author , Kathleen CapaccioneKathleen Capaccione More articles by this author , Min YangMin Yang More articles by this author , Derek AdlerDerek Adler More articles by this author , Derek GordonDerek Gordon More articles by this author , Joseph BaroneJoseph Barone More articles by this author , David GoldfarbDavid Goldfarb More articles by this author , Jay TischfieldJay Tischfield More articles by this author , and Amrik SahotaAmrik Sahota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2277AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Slc3a1 knockout mice (KO) are a model for human cystinuria and male mice beginning at age 3 months develop urinary tract stones. Computed tomography (CT) and magnetic resonance imaging (MRI) may allow us to follow stone growth and the effects of drug treatment in live animals. We evaluated the utility of these modalities for identifying cystine stone growth in Slc3a1 KO mice and for assessing the efficacy of cystine dimethyl ester (CDME), a cystine crystal growth inhibitor. METHODS Male mice were screened for bladder stones using the Albira CT scanner and the Aspect 2 MRI scanner. Initial bladder volume (an indicator of stone volume) was calculated using InviCRO VivoQuant software. Mice with stones were randomly assigned to treatment (200 μl of 10 mg/ml CDME, n=11) or control (200 μl water, n=7) groups, each given daily by gavage for 10 weeks. Volume measurements were repeated at 1-2 week intervals. Mice were then sacrificed and stone size and number analyzed using chi-square. RESULTS 60% of mice had bladder stones. Using CT, initial bladder volumes (mm3) in both groups were similar (12-96 for control and 11-86 for CDME). In both cases, there was a linear increase in stone volume that followed the equation y=mx+c. The equations for the CDME and the control groups were similar (range y=0.39x+11.0 to y=2.67x+73.3). Final MRI scans demonstrated a 15.5% and a 12.4% increase in kidney volume for the two groups, respectively, (p=.17). Thus, the two groups could not be distinguished by CT or MRI analysis. Upon histologic evaluation there was a significant difference in the percentage of stone sizes in the two groups (p=0.05). The treatment group had 9.4% more stones and the control group had 19.6% fewer stones in the 1.1-2.0 mm range. The treatment group had 26.1% fewer stones and the control group had 54.6% more stones in the 3.1-4.0 mm range. CONCLUSIONS CT can determine the rate of stone growth in vivo, but longitudinal measurement of stone volume is not suitable for evaluating CDME efficacy since total stone volumes in both groups were comparable. MRI was also unable to differentiate the two groups. These imaging modalities are useful for differentiating stone formers form non-stone formers, but cannot be used for the assessment of pharmacological intervention. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e838 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Jaspreet Parihar More articles by this author Kathleen Capaccione More articles by this author Min Yang More articles by this author Derek Adler More articles by this author Derek Gordon More articles by this author Joseph Barone More articles by this author David Goldfarb More articles by this author Jay Tischfield More articles by this author Amrik Sahota More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...