RT Journal Article SR Electronic T1 A Vaccinia Virus Encoding the Human Sodium Iodide Symporter Facilitates Long-Term Image Monitoring of Virotherapy and Targeted Radiotherapy of Pancreatic Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1933 OP 1942 DO 10.2967/jnumed.112.105056 VO 53 IS 12 A1 Dana Haddad A1 Pat B. Zanzonico A1 Sean Carlin A1 Chun-Hao Chen A1 Nanhai G. Chen A1 Qian Zhang A1 Yong A. Yu A1 Valerie Longo A1 Kelly Mojica A1 Richard J. Aguilar A1 Aladar A. Szalay A1 Yuman Fong YR 2012 UL http://jnm.snmjournals.org/content/53/12/1933.abstract AB To assess therapeutic response and potential toxicity of oncolytic virotherapy, a noninvasive, deep-tissue imaging modality is needed. This study aimed to assess the feasibility, parameters, and determining factors of serial imaging and long-term monitoring of virotherapy and the therapeutic response of pancreatic cancer xenografts treated with a vaccinia virus carrying the human sodium iodide symporter GLV-1h153. Methods: Pancreatic cancer xenografts (PANC-1) in nude mice were treated systemically or intratumorally with GLV-1h153 and serially imaged using 124I PET at 1, 2, 3, and 5 wk after viral injection. Signal intensity was compared with tumor therapeutic response and optical imaging, and tumors were histologically analyzed for morphology and the presence of virus. Autoradiography was performed using technetium-pertechnetate and γ-scintigraphy to assess determining factors for radiouptake in tumors. Finally, the enhanced therapeutic effect of combination therapy with GLV-1h153 and systemic radioiodine was assessed. Results: GLV-1h153 successfully facilitated serial long-term imaging of virotherapy, with PET signal intensity correlating to tumor response. GLV-1h153 colonization of tumors mediated radioiodine uptake at potentially therapeutic doses. Successful radiouptake required the presence of virus, adequate blood flow, and viable tissue, whereas loss of signal intensity was linked to tumor death and necrosis. Finally, combining systemically administered GLV-1h153 and 131I led to enhanced tumor kill when compared with virus or 131I alone (P < 0.01). Conclusion: GLV-1h153 is a promising oncolytic agent for the treatment, long-term imaging, and monitoring of therapeutic response in a xenograft model of pancreatic cancer. GLV-1h153 provided insight into tumor biologic activity and facilitated enhanced tumor kill when combined with systemic targeted radiotherapy. These results warrant further investigation into parameters and potential synergistic effects of combination therapy.