TY  - JOUR
A1  - Haddad, Dana
A1  - Chen, Chun-Hao
A1  - Carlin, Sean
A1  - Silberhumer, Gerd
A1  - Chen, Nanhai G.
A1  - Zhang, Qian
A1  - Longo, Valerie
A1  - Carpenter, Susanne G.
A1  - Mittra, Arjun
A1  - Carson, Joshua
A1  - Au, Joyce
A1  - Gonen, Mithat
A1  - Zanzonico, Pat B.
A1  - Szalay, Aladar A.
A1  - Fong, Yuman
T1  - Imaging Characteristics, Tissue Distribution, and Spread of a Novel Oncolytic Vaccinia Virus Carrying the Human Sodium Iodide Symporter
JF  - PLoS One
N2  - Introduction: Oncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS. 
Methods: GLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide \(^{131}\)I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via \(^{124}\)I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both \(^{124}\)I-PET and 99m-technecium gamma-scintigraphy. 
Results: GLV-1h153 successfully facilitated time-dependent intracellular uptake of \(^{131}\)I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P < 0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10\(^9\) plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean % ID/gm of 3.82 \(\pm\) 60.46 (P < 0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV1h153-infected tumors were detected via \(^{124}\)I-PET and 99m-technecium-scintigraphy. 
Conclusion: GLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality.
KW  - nude mice
KW  - pancreatic cancer
KW  - engineered measles-virus
KW  - positron-emission-tomography
KW  - malignant pleural mesothelioma
KW  - reporter gene
KW  - replicating adenovirus
KW  - NA/I symporter
KW  - breast cancer
KW  - viral therapy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130041
VL  - 7
IS  - 8
ER  -