title: Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma.
abstract: High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.|Division of Nuclear Medicine, Hôpital de la Cité-de-la-Santé de Laval, QC, H7M 3L9, Canada.
authors.forename: Khun Visith
authors.initials: KV
authors.lastname: Keu
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.|Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, WC1E 6DD, UK.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Witney
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Yaghoubi
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.
authors.forename: Jarrett
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Neurosurgery, City of Hope, Duarte, CA, 91010, United States.
authors.forename: Anita
authors.initials: A
authors.lastname: Kurien
authors.affiliation: Neurosurgery, City of Hope, Duarte, CA, 91010, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: Magnusson
authors.affiliation: Molecular & Medical Pharmacology, UCLA, Los Angeles, CA, 90095, United States.
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.
authors.forename: Frezghi
authors.initials: F
authors.lastname: Habte
authors.affiliation: Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 91010, United States.
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Wagner
authors.affiliation: Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 91010, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.affiliation: Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 91010, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Brown
authors.affiliation: Molecular & Medical Pharmacology, UCLA, Los Angeles, CA, 90095, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Allen-Auerbach
authors.affiliation: Molecular & Medical Pharmacology, UCLA, Los Angeles, CA, 90095, United States.
authors.forename: Johannes
authors.initials: J
authors.lastname: Czernin
authors.affiliation: Sangamo BioSciences Inc, Richmond, CA 94804, United States.
authors.forename: Winson
authors.initials: W
authors.lastname: Tang
authors.affiliation: Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, 98145, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
authors.affiliation: Neurosurgery, City of Hope, Duarte, CA, 91010, United States.
authors.forename: Behnam
authors.initials: B
authors.lastname: Badie
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University, Palo Alto, CA, 94305, United States.|Department of Bioengineering, Department of Materials Science & Engineering, Bio-X, Stanford University, Palo Alto, CA, 94305, United States.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000000981:diagnostic imaging* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018793:Interleukin-13 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D013937:Thymidine Kinase / Q000378:metabolism
chemical_list: C578095:IL13 protein, human; D018793:Interleukin-13; D011948:Receptors, Antigen, T-Cell; D013937:Thymidine Kinase