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Open Access Research article

Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging

Ali S Arbab12*, Christine Thiffault3, Bradford Navia4, Stephen J Victor4, Klaudyne Hong3, Li Zhang5, Quan Jiang5, Nadimpalli RS Varma1, ASM Iskander1 and Michael Chopp56

Author Affiliations

1 Department of Radiology, Cellular and Molecular Imaging Laboratory, Henry Ford Hospital, Detroit, MI 48202, USA

2 Department of Radiology, Wayne State University School of Medicine, Detroit, MI, USA

3 Advanced Technologies and Regenerative Medicine, LLC, a Johnson & Johnson Co., Route 22 West, P.O. Box 151, Somerville, NJ 08876-0151, USA

4 Eisai, Inc, 155 Tice Blvd, Woodcliff Lake, NJ 07677, USA

5 Department of Neurology, Henry Ford Hospital, Detroit, MI, USA

6 Department of Physics, Oakland University, Rochester, MI, USA

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BMC Medical Imaging 2012, 12:33  doi:10.1186/1471-2342-12-33

Published: 6 December 2012

Abstract

Background

In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available in vivo cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT).

Methods

Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals underwent SPECT imaging on days 0, 1, and 3. Radioactivity in various organs as well as in the stroke area and contralateral hemisphere was determined, decay corrected and normalized to the total (whole body including head) radioactivity on day 0. Immunohistochemical analysis was also performed to confirm the beneficial effects of hUTC on vascular and synaptic density, and apoptosis.

Results

Most of the radioactivity (43.36±23.07% on day 0) trafficked to the lungs immediately following IV administration of In-111 labeled hUTC (day 0) and decreased drastically to 8.81±7.75 and 4.01±4.52% on days 1 and 3 post-injection, respectively. In contrast, radioactivity measured in the lung of animals that received In-111-oxine alone remained relatively unchanged from day 0 to day 1 (18.38±5.45% at day 0 to 12.59±5.94%) and decreased to 8.34±4.25% on day 3. Significantly higher radioactivity was observed in stroke areas of animals that received In-111 labeled hUTC indicating the presence of cells at the site of injury representing approximately 1% of total administered dose. In addition, there was significant increase in vascular and synaptophysin immunoreactivity in stroke areas of rats that received In-111 labeled hUTC.

Conclusions

The present studies showed the tracking of In-111 labeled hUTC to the sites of stroke in a rat model of tMCAo using SPECT. Animals treated with In-111 labeled hUTC showed histological improvements, with higher vascular and synaptic densities observed in the ischemic boundary zone (IBZ).

Keywords:
Human umbilical tissue-derived cells (hUTC); In-111-oxine; SPECT; Cell tracking; Stroke rats