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Noninvasive detection of therapeutic cytolytic T cells with 18F–FHBG PET in a patient with glioma

Nature Clinical Practice Oncology volume 6, pages 53–58 (2009)Cite this article

Abstract

Background A 57-year-old man had been diagnosed with grade IV glioblastoma multiforme and was enrolled in a trial of adoptive cellular immunotherapy. The trial involved infusion of ex vivo expanded autologous cytolytic CD8+ T cells (CTLs), genetically engineered to express the interleukin 13 zetakine gene (which encodes a receptor protein that targets these T cells to tumor cells) and the herpes simplex virus 1 thymidine kinase (HSV1 tk) suicide gene, and PET imaging reporter gene.

Investigations MRI, whole-body and brain PET scan with 18F-radiolabelled 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine (18F–FHBG) to detect CTLs that express HSV1 tk, and safety monitoring after injection of 18F–FHBG.

Diagnosis MRI detected grade III–IV glioblastoma multiforme plus two tumors recurrences that developed after resection of the initial tumor.

Management Surgical resection of primary glioblastoma tumor, enrollment in CTL therapy trial, reresection of glioma recurrences, infusion of approximately 1 × 109 CTLs into the site of tumor reresection, and 18F–FHBG PET scan to detect infused CTLs.

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Figure 1: MRI, and PET over MRI superimposed brain images, of the patient who received infusions of autologous cytolytic T cells that expressed interleukin 13 zetakine and herpes simplex virus 1 thymidine kinase genes.
Figure 2: Whole-body PET and combined PET and CT images of 18F–FHBG biodistribution in a glioma patient, 2 h after intravenous injection.
Figure 3: Uptake of 3H-labelled penciclovir into the genetically engineered CTLs that were infused into the patient and into control Jurkat cells.

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Acknowledgements

SSG has received funding from NIH NCI ICMIC P50, RO1 CA135486, and Doris Duke Charitable Foundation. MCJ has received funding from NIH RO1 CA103959. The authors thank Brenda Williams at COHNMC, Larry Pang and technologists at UCLA nuclear medicine clinics, the UCLA cyclotron crew, and Drs Martin Allen-Auerbach and Christian Schiepers for providing support with the patient study at UCLA. We also thank Yingbing Wang, Rhona Berganos, Dr Michael Goris, Dr Fred Chin, Dr Mohammad Namavari, Dr Murugessan Subbarayan, Dr Erik Mitra, Dr Andrei Iagaru, Dr Larry Recht and the many involved Stanford University nuclear medicine clinic technologists.

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Authors and Affiliations

  1. SS Yaghoubi is a Research Scientist in the Multimodality Molecular Imaging Lab; D Paik is Assistant Professor of Diagnostic Radiology in the Department of Radiology, Division Chief of Nuclear Medicine Division and Professor of Department of Radiology & Bioengineering, Bio-X and Molecular Imaging Programs; SS Gambhir is Director of the Molecular Imaging Program, all at Stanford, CA.,

    Shahriar S Yaghoubi, Shradha Budhiraja, David Paik & Sanjiv S Gambhir

  2. S Budhiraja is in the Department of Radiology, Bio-X and Molecular Imaging Programs,

    Shahriar S Yaghoubi, Shradha Budhiraja, David Paik & Sanjiv S Gambhir

  3. MC Jensen is Co-Director of the Cancer Immunotherapeutics & Tumor Immunology program and Director of Pediatric Neuro-oncology at City of Hope Medical Center, CA.,

    Michael C Jensen

  4. N Satyamurthy is Professor of Molecular & Medical Pharmacology,

    Nagichettiar Satyamurthy & Johannes Czernin

  5. J Czernin is Director of the Nuclear Medicine Clinic, Positron Emission Tomography/Computed Tomography and Professor and Vice Chair of Molecular & Medical Pharmacology at UCLA, CA, USA.,

    Nagichettiar Satyamurthy & Johannes Czernin

Authors
  1. Shahriar S Yaghoubi
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  2. Michael C Jensen
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  7. Sanjiv S Gambhir
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Corresponding author

Correspondence to Sanjiv S Gambhir.

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The authors declare no competing financial interests.

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Yaghoubi, S., Jensen, M., Satyamurthy, N. et al. Noninvasive detection of therapeutic cytolytic T cells with 18F–FHBG PET in a patient with glioma. Nat Rev Clin Oncol 6, 53–58 (2009). https://doi.org/10.1038/ncponc1278

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