RT Journal Article
SR Electronic
T1 Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 221
OP 227
DO 10.2967/jnumed.116.180463
VO 58
IS 2
A1 Jiahu Wang
A1 Rozanne Arulanandam
A1 Richard Wassenaar
A1 Theresa Falls
A1 Julia Petryk
A1 Judith Paget
A1 Kenneth Garson
A1 Catia Cemeus
A1 Barbara C. Vanderhyden
A1 R. Glenn Wells
A1 John C. Bell
A1 Fabrice Le Boeuf
YR 2017
UL http://jnm.snmjournals.org/content/58/2/221.abstract
AB Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biologic agent, OV has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in preclinical models and in clinical trials. To give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral-based platforms with 2 specific gene reporters. Methods: We incorporated the human sodium iodide symporter (hNIS) and the human somatostatin receptor 2 (hSSR2) in the vaccinia-based OV and tested viral constructs for their abilities to track and treat tumor development in vivo. Results: Early and high-level expression of hNIS is detrimental to the recombinant virus, leading to the aggregation of hNIS protein and early cell death. Putting hNIS under a late synthetic promoter allowed a higher functional expression of the protein and much stronger 123I or 99Tc uptake. In vivo, the hNIS-containing virus infected and amplified in the tumor site, showing a better efficacy than the parental virus. The hNIS expression at the tumor site allowed for the imaging of viral infection and tumor regression. Similarly, hSSR2-containing OV vaccinia infected and lysed cancer cells. Conclusion: When tumor-bearing mice were given hNIS- and hSSR2-containing OV, 99Tc and 111In signals coalesced at the tumor, highlighting the power of using these viruses for tumor diagnosis and treatment.