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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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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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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DOI: https://doi.org/10.1038/ncponc1278
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