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


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


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


RESULTS
Surgical resection of primary glioblastoma tumor, enrollment in CTL therapy trial, reresection of glioma recurrences, infusion of approximately 1 x 10(9) CTLs into the site of tumor reresection, and (18)F-FHBG PET scan to detect infused CTLs.
Yaghoubi
Shahriar S
SS
Multimodality Molecular Imaging Lab, Department of Radiology & Bioengineering, Stanford University, Stanford, CA, USA.
Jensen
Michael C
MC
Satyamurthy
Nagichettiar
N
Budhiraja
Shradha
S
Paik
David
D
Czernin
Johannes
J
Gambhir
Sanjiv S
SS
D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000628:therapy; D005462:Fluorine Radioisotopes / Q000008:administration & dosage; D015316:Genetic Therapy; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000276:immunology / Q000628:therapy; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D005462:Fluorine Radioisotopes; D006147:Guanine; D013937:Thymidine Kinase