Cell therapy in murine atherosclerosis: in vivo imaging with high-resolution helical SPECT.
OBJECTIVE
To determine the feasibility of in vivo localization and quantification of indium 111 (111In)-oxine-labeled bone marrow (BM) with high-resolution whole-body helical single photon emission computed tomography (SPECT) in an established murine model of atherosclerosis and vascular repair.


METHODS
The institutional animal care and use committee approved this study. BM from young B6 Rosa 26 Lac Z+/+ mice was radiolabeled with 111In-oxine. On days 1, 4, and 7 after administration of radiolabeled cells, five C57/BL6 apolipoprotein E-deficient mice and five wild-type (WT) control mice were imaged with whole-body high-resolution helical SPECT. Quantification with SPECT was compared with ex vivo analysis by means of gamma counting. Autoradiography and beta-galactosidase staining were used to verify donor cell biodistribution. Linear regression was used to assess the correlation between continuous variables. Two-tailed Student t test was used to compare values between groups, and paired two-tailed t test was used to assess changes within subjects at different time points.


RESULTS
SPECT image contrast was high, with clear visualization of BM, liver, and spleen 7 days after administration of radiolabeled cells. SPECT revealed that 42% and 58% more activity was localized to the aorta and BM (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. Furthermore, 28% and 27% less activity was localized to the liver and spleen (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. SPECT and organ gamma counts showed good quantitative correlation (r=0.9). beta-Galactosidase staining and microautoradiography of recipient aortas showed donor cell localization to the intima of visible atherosclerotic plaque but not to unaffected regions of the vessel wall.


CONCLUSIONS
High-resolution in vivo helical pinhole SPECT can be used to monitor and quantify early biodistribution of 111In-oxine-labeled BM in a murine model of progenitor cell therapy for atherosclerosis.
Vemulapalli
Sreekanth
S
Department of Medicine, Division of Cardiology, Duke University Medical Center, Box 3808 DUMC, Durham, NC 27710, USA.
Metzler
Scott D
SD
Akabani
Gamal
G
Petry
Neil A
NA
Niehaus
Nelsen J
NJ
Liu
Xialin
X
Patil
Nikhil H
NH
Greer
Kim L
KL
Jaszczak
Ronald J
RJ
Coleman
R Edward
RE
Dong
Chunming
C
Goldschmidt-Clermont
Pascal J
PJ
Chin
Bennett B
BB
D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000601:surgery*; D001854:Bone Marrow Cells / Q000000981:diagnostic imaging*; D016026:Bone Marrow Transplantation / Q000000981:diagnostic imaging* / Q000379:methods; D004195:Disease Models, Animal; D005240:Feasibility Studies; D007089:Image Enhancement / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives*; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C032950:indium oxine; D015125:Oxyquinoline