title: In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation.
abstract: Cancer surgery requires the complete and precise identification of malignant tissue margins including the smallest disseminated lesions. Internal green fluorescent protein (GFP) fluorescence can intensely illuminate even single cells but requires GFP sequence transcription within the cell. Introducing and selectively activating the GFP gene in malignant tissue in vivo is made possible by the development of OBP-401, a telomerase-dependent, replication-competent adenovirus expressing GFP. This potentially powerful adjunct to surgical navigation was demonstrated in 2 nude mouse models that represent difficult surgical challenges--the resection of widely disseminated cancer. HCT-116, a model of intraperitoneal disseminated human colon cancer, was labeled by virus injection into the peritoneal cavity. A549, a model of pleural dissemination of human lung cancer, was labeled by virus administered into the pleural cavity. Only the malignant tissue fluoresced brightly in both models. In the intraperitoneal model of disseminated cancer, fluorescence-guided surgery enabled resection of all tumor nodules labeled with GFP by OBP-401. The data in this report suggest that adenoviral-GFP labeling tumors in patients can enable fluorescence-guided surgical navigation.
authors.affiliation: AntiCancer, Inc, San Diego, CA 92111, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Urata
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Sheldon
authors.initials: S
authors.lastname: Penman
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D019060:Minimally Invasive Surgical Procedures / Q000379:methods*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D019098:Telomerase / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D019098:Telomerase
references.citation: Oncogene. 2005 Apr 28;24(19):3130-40
references.pmid: 15735729
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):285-92
references.pmid: 14734481
references.citation: Biotechniques. 2005 Aug;39(2):170, 172
references.pmid: 16116787
references.citation: J Clin Oncol. 2004 Aug 15;22(16):3284-92
references.pmid: 15310771
references.citation: Cancer. 2000 Jan 15;88(2):358-63
references.pmid: 10640968
references.citation: Cancer Res. 2004 Sep 1;64(17):6259-65
references.pmid: 15342413
references.citation: Oncology (Williston Park). 2004 Feb;18(2):207-19; discussion 220-2, 227-8, 230
references.pmid: 15008058
references.citation: Nat Protoc. 2006;1(2):928-35
references.pmid: 17406326
references.citation: Nat Protoc. 2006;1(3):1429-38
references.pmid: 17406431
references.citation: Nat Med. 2006 Oct;12(10):1213-9
references.pmid: 17013385
references.citation: Nat Rev Cancer. 2005 Oct;5(10):796-806
references.pmid: 16195751
references.citation: J Environ Pathol Toxicol Oncol. 2007;26(2):157-64
references.pmid: 17725542
references.citation: Nat Protoc. 2006;1(2):775-82
references.pmid: 17406307
references.citation: Int J Cancer. 2006 Jul 15;119(2):432-40
references.pmid: 16477640
references.citation: Cancer Res. 2006 Apr 15;66(8):4208-14
references.pmid: 16618743
references.citation: Oncology (Williston Park). 2004 Jan;18(1):51-9
references.pmid: 14768406