Positron emission tomography imaging for herpes virus infection: Implications for oncolytic viral treatments of cancer

Abstract

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 [124I]-5-iodo-2′-fluoro-1-β-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 × 107 viral particles injected into a 0.5-cm human colorectal tumor can be detected by [124I]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.

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Figure 2: FIAU accumulation rates (Ki FIAU) demonstrate viral TK activity in HCT8 cells after infection with each of 3 HSV-1 recombinants.
Figure 3: Transaxial PET images of viral-treated human colorectal flank tumors.
Figure 4: Histochemistry and autoradiography of viral treated tumors.
Figure 1: Genomic structure for wild-type HSV-1(F) strain virus and 3 derivative recombinants.

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Acknowledgements

This work was supported in part by grants RO1CA75416, RO1CA72632, and RO1CA61524 (to Y.F.) and RO1CA69769, R24CA83084 and P50CA86438 (R.B.) from the National Institutes of Health; grant MBC-99366 from the American Cancer Society; and grant DE-FG02-86ER60407 06 from the Department of Energy (to R.F.).

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Correspondence to Yuman Fong.

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Bennett, J., Tjuvajev, J., Johnson, P. et al. Positron emission tomography imaging for herpes virus infection: Implications for oncolytic viral treatments of cancer. Nat Med 7, 859–863 (2001). https://doi.org/10.1038/89991

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