This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuruppu, D. Articles by Tanabe, K. K. Search for Related Content PubMed PubMed Citation Articles by Kuruppu, D. Articles by Tanabe, K. K.

Positron Emission Tomography of Herpes Simplex Virus 1 Oncolysis

¹ Division of Surgical Oncology and ² Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Kenneth K. Tanabe, Division of Surgical Oncology, Massachusetts General Hospital, Yawkey 7.924, 55 Fruit Street, Boston, MA 02114. Phone: 617-724-3868; Fax: 617-724-3895; E-mail: ktanabe{at}partners.org.

Viral oncolysis, the destruction of cancer cells by replicating viruses, is under clinical investigation for cancer therapy. Lytic viral replication in cancer cells both destroys the cells and liberates progeny virion to infect adjacent cancer cells. The safety and efficacy of this approach are dependent on selective and robust viral replication in cancer cells rather than in normal cells. Methods to detect and quantify viral replication in tissues have relied on organ sampling for molecular analyses. Preclinical and clinical studies of viral oncolysis will benefit significantly from development of a noninvasive method to repetitively measure viral replication. We have shown that positron emission tomography (PET) allows for in vivo detection of herpes simplex virus (HSV)-1 replication in tumor cells using 9-(4-[¹⁸F]-fluoro-3-[hydroxymethyl]butyl)guanine ([¹⁸F]FHBG) as the substrate for HSV thymidine kinase (HSV-TK). As expected, phosphorylated [¹⁸F]FHBG is initially trapped within HSV-1–infected tumor cells and is detectable as early as 2 h following virus administration. MicroPET images reveal that [¹⁸F]FHBG accumulation in HSV-1–infected tumors peaks at 6 h. However, despite progressive accumulation of HSV-1 titers and HSV-TK protein in the tumor as viral oncolysis proceeds, tumor cell degradation resulting from viral oncolysis increases over time, which limits intracellular retention of [¹⁸F]FHBG. These observations have important consequences with regard to strategies to use [¹⁸F]FHBG PET for monitoring sites of HSV-TK expression during viral oncolysis. [Cancer Res 2007;67(7):3295–300]

This article has been cited by other articles:

				J. Veerapong, K. A. Bickenbach, M. Y. Shao, K. D. Smith, M. C. Posner, B. Roizman, and R. R. Weichselbaum Systemic Delivery of {gamma}134.5-Deleted Herpes Simplex Virus-1 Selectively Targets and Treats Distant Human Xenograft Tumors That Express High MEK Activity Cancer Res., September 1, 2007; 67(17): 8301 - 8306. [Abstract] [Full Text] [PDF]