title: Imaging of lymph node micrometastases using an oncolytic herpes virus and [F]FEAU PET.
abstract: BACKGROUND
  In patients with melanoma, knowledge of regional lymph node status provides important information on outlook. Since lymph node status can influence treatment, surgery for sentinel lymph node (SLN) biopsy became a standard staging procedure for these patients. Current imaging modalities have a limited sensitivity for detection of micrometastases in lymph nodes and, therefore, there is a need for a better technique that can accurately identify occult SLN metastases.
  
  
  RESULTS
  B16-F10 murine melanoma cells were infected with replication-competent herpes simplex virus (HSV) NV1023. The presence of tumor-targeting and reporter-expressing virus was assessed by [(18)F]-2'-fluoro-2'-deoxy-1-beta-D-beta-arabinofuranosyl-5-ethyluracil ([(18)F]FEAU) positron emission tomography (PET) and confirmed by histochemical assays. An animal foot pad model of melanoma lymph node metastasis was established. Mice received intratumoral injections of NV1023, and 48 hours later were imaged after i.v. injection of [(18)F]FEAU. NV1023 successfully infected and provided high levels of lacZ transgene expression in melanoma cells. Intratumoral injection of NV1023 resulted in viral trafficking to melanoma cells that had metastasized to popliteal and inguinal lymph nodes. Presence of virus-infected tumor cells was successfully imaged with [(18)F]FEAU-PET, that identified 8 out of 8 tumor-positive nodes. There was no overlap between radioactivity levels (lymph node to surrounding tissue ratio) of tumor-positive and tumor-negative lymph nodes.
  
  
  CONCLUSIONS
  A new approach for imaging SLN metastases using NV1023 and [(18)F]FEAU-PET was successful in a murine model. Similar studies could be translated to the clinic and improve the staging and management of patients with melanoma.
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Brader
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Kelly
authors.forename: Sheng
authors.initials: S
authors.lastname: Gang
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
authors.forename: Hedvig
authors.initials: H
authors.lastname: Hricak
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Blasberg
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Ziv
authors.initials: Z
authors.lastname: Gil
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives; D006564:Herpesviridae; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging* / Q000473:pathology; D008546:Melanoma, Experimental / Q000175:diagnosis; D051379:Mice; D050504:Oncolytic Viruses; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D001086:Arabinofuranosyluracil; C054103:2'-fluoro-5-ethylarabinosyluracil