Molecular imaging of gene transduction in cardiac transplantation

Rao, Vinay P.

Medicine
July 2012

Thesis or dissertation


Rights
© 2012 Vinay P Rao. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

This thesis is based on a series of experiments aimed at designing a model of gene transfer to the transplanted heart. The use of viral vector-based gene therapy to target pathological processes following cardiac transplantation faces many challenges including the potential effects of the virus on the host as well as the need to establish the presence of the gene in the target organ. In the first set of
experiments (Chapter 2), concerns over the effects of adenoviral gene transfer on the later development of cardiac allograft vasculopathy (CAV) were addressed. Heterotopically transplanted cardiac allografts from Brown Norway to Lewis rats revealed the presence of CAV at 120 days. Ex vivo adenoviral serotype 5 perfusion of the donor heart did not affect the later development of allograft
vasculopathy.

In the second series of experiments, the feasibility of visualizing the presence of the sodium iodide symporter (hNIS) non-invasively following its gene transduction was established with the use of SPECT imaging. Following gene transfer, the recipients were injected with ⁹⁹mTc in the first set of experiments (Chapter 3) or with radioactive ¹²³I (Chapter 4) and imaged under a SPECT scanner. Radioactive isotope uptake in the Ad-NIS group was significantly higher than in the group of animals whose hearts were perfused with just University of Wisconsin solution or with blank adenovirus without a marker gene. Sequential imaging of Ad-NIS-perfused hearts between post-operative days 2 and 14 revealed peak image intensity at day 5. Overall, image intensities correlated with ex vivo counts of radioactivity.

These data demonstrate that hNIS is an excellent reporter gene whose expression can be accurately and non-invasively monitored by serial radioisotope single photon emission computed tomography (SPECT) imaging.

Publisher
Postgraduate Medical Institute, The University of Hull
Supervisor
McCollum, Peter T.; Chetter, Ian
Qualification level
Doctoral
Qualification name
MD
Language
English
Extent
Filesize: 3 MB
Identifier
hull:7165
QR Code