Molecular imaging of gene transduction in cardiac transplantation

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 ofexperiments (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 allograftvasculopathy.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.

Name dc:type.qualificationname

MD

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Hull

Year dc:date.issued

2012

Author dc:creator

• Rao, Vinay P.

Advisors dc:contributor.advisor

• McCollum, Peter T.
• Chetter, Ian

• Medicine

Language dc:language

en

Identifier

oai:hull-repository.worktribe.com:4214665

OAI identifier oai:identifier

oai:hull-repository.worktribe.com:4214665