Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
BACKGROUND
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 ± 0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via (124)I-PET and 99m-technecium-scintigraphy.


CONCLUSIONS
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.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Dana
D
Haddad
Chun-Hao
CH
Chen
Sean
S
Carlin
Gerd
G
Silberhumer
Nanhai G
NG
Chen
Qian
Q
Zhang
Valerie
V
Longo
Susanne G
SG
Carpenter
Arjun
A
Mittra
Joshua
J
Carson
Joyce
J
Au
Mithat
M
Gonen
Pat B
PB
Zanzonico
Aladar A
AA
Szalay
Yuman
Y
Fong
D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D051379:Mice; D057054:Molecular Imaging; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology*; D061848:Optical Imaging; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000821:virology; D049268:Positron-Emission Tomography; D027981:Symporters / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution; D014616:Vaccinia virus / Q000235:genetics* / Q000502:physiology*; D014779:Virus Replication; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters