Cell therapy in murine atherosclerosis: in vivo imaging with high-resolution helical SPECT.

Abstract

PURPOSE:

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.

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: Sreekanth Vemulapalli, Scott D Metzler, Gamal Akabani, Neil A Petry, Nelsen J Niehaus, Xialin Liu, Nikhil H Patil, Kim L Greer, Ronald J Jaszczak, R Edward Coleman, Chunming Dong, Pascal J Goldschmidt-Clermont, Bennett B Chin
• Journal: Radiology (Radiology) Vol. 242 Issue 1 Pg. 198-207 (Jan 2007) ISSN: 0033-8419 [Print] United States
• PMID: 17185668 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) RSNA, 2007.

Chemical References

• Organometallic Compounds
• Radiopharmaceuticals
• indium oxine
• Oxyquinoline

Topics

• Animals
• Atherosclerosis (diagnostic imaging, surgery)
• Bone Marrow Cells (diagnostic imaging)
• Bone Marrow Transplantation (diagnostic imaging, methods)
• Disease Models, Animal
• Feasibility Studies
• Image Enhancement (methods)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Organometallic Compounds
• Oxyquinoline (analogs & derivatives)
• Radiopharmaceuticals
• Tomography, Emission-Computed, Single-Photon (methods)