Monitoring the initial delivery of an oncolytic measles virus encoding the human sodium iodide symporter to solid tumors using contrast-enhanced computed tomography

• Published in: The journal of gene medicine Vol. 14; no. 9-10; pp. 590 - 597
• Main Authors: Penheiter, Alan R., Dingli, David, Bender, Claire E., Russell, Stephen J., Carlson, Stephanie K.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-09-2012; Wiley Periodicals Inc
• Subjects: Animals; Contrast Media; Female; Gene therapy; Humans; iodinated contrast agent; Measles virus - genetics; Mice; Mice, Nude; Neoplasms, Experimental - diagnosis; Neoplasms, Experimental - genetics; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - therapy; Omnipaque; oncolytic measles; Oncolytic Viruses - genetics; pancreatic cancer; Sodium Pertechnetate Tc 99m; sodium-iodide symporter; SPECT/CT; Symporters - administration & dosage; Symporters - genetics; Symporters - pharmacokinetics; Tomography, Emission-Computed, Single-Photon - methods; X-Ray Microtomography - methods; Xenograft Model Antitumor Assays
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.2670

Background
We aimed to determine the feasibility of monitoring viral delivery and initial distribution to solid tumors using iodinated contrast agent and micro‐computed tomography (CT).
Methods
Human BxPC‐3 pancreatic tumor xenografts were established in nude mice. An oncolytic measles virus with an additional transcriptional unit encoding the sodium iodide symporter (NIS), as a reporter for viral infection, was mixed with a 1:10 dilution of Omnipaque 300 (GE Healthcare, Milwaukee, WI, USA) contrast agent and injected directly into tumors. Mice were imaged with micro‐CT immediately before and after injection to determine the location of contrast agent/virus mixture. Mice were imaged again on day 3 after injection with micro‐single‐photon emission CT/CT to determine the location of NIS‐mediated 99mTcO4 transport.
Results
A 1:10 dilution of Omnipaque had no effect on viral infectivity or cell viability in vitro and was more than adequate for CT imaging of the intratumoral injectate distribution. The volume of tumor coverage with initial CT contrast agent and the 3‐day postinfection measurement of virally infected tumor volume were significantly correlated. Additionally, regions of the tumor that did not receive contrast agent from the initial injection were largely devoid of viral infection at early time points.
Conclusions
Contrast‐enhanced viral delivery enables a rapid and accurate prediction of the initial viral distribution within a solid tumor. This technique should enable real‐time monitoring of viral propagation from initially infected tumor regions to adjacent tumor regions. Copyright © 2012 John Wiley & Sons, Ltd.