Positron emission tomography imaging for herpes virus infection: Implications for oncolytic viral treatments of cancer.
Molecular therapy using viruses would benefit greatly from a non-invasive modality for assessing dissemination of viruses. Here we investigated whether positron emission tomography (PET) scanning using [(124)I]-5-iodo-2'-fluoro-1-beta-d-arabinofuranosyl-uracil (FIAU) could image cells infected with herpes simplex viruses (HSV). Using replication-competent HSV-1 oncolytic viruses with thymidine kinase (TK) under control of different promoters, we demonstrate that viral infection, proliferation and promoter characteristics all interact to influence FIAU accumulation and imaging. In vivo, as few as 1 x 107 viral particles injected into a 0.5-cm human colorectal tumor can be detected by [(124)I]FIAU PET imaging. PET signal intensity is significantly greater at 48 hours compared with that at 8 hours after viral injection, demonstrating that PET scanning can detect changes in TK activity resulting from local viral proliferation. We also show the ability of FIAU-PET scanning to detect differences in viral infectivity at 0.5 log increments. Non-invasive imaging might be useful in assessing biologically relevant distribution of virus in therapies using replication-competent HSV.
Bennett
J J
JJ
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Tjuvajev
J
J
Johnson
P
P
Doubrovin
M
M
Akhurst
T
T
Malholtra
S
S
Hackman
T
T
Balatoni
J
J
Finn
R
R
Larson
S M
SM
Federoff
H
H
Blasberg
R
R
Fong
Y
Y
D000998:Antiviral Agents / Q000627:therapeutic use; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001345:Autoradiography; D001691:Biological Therapy; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic; D013937:Thymidine Kinase / Q000235:genetics; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase