title: Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging.
abstract: Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of the cancer. Since activated T lymphocytes may serve as a hallmark for anticancer responses, we targeted these cells using the radiotracer N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL-2) for positron emission tomography (PET) imaging. Thus, we noninvasively monitored the effects of local tumor irradiation and/or immunization on tumor-infiltrating and systemic activated lymphocytes in tumor-bearing mice. A 10- and 27-fold higher [18F]FB-IL-2 uptake was observed in tumors of mice receiving tumor irradiation alone or in combination with immunization, respectively. This increased uptake was extended to several non-target tissues. Administration of the CXCR4 antagonist AMD3100 reduced tracer uptake by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes upon cancer treatment. In conclusion, [18F]FB-IL-2 PET can serve as a clinical biomarker to monitor treatment-induced infiltration of activated T lymphocytes and, on that basis, may guide cancer immunotherapies.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: S V
authors.initials: SV
authors.lastname: Hartimath
authors.affiliation: Department of Medical Microbiology, Tumor Virology and Cancer Immunotherapy, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: O
authors.initials: O
authors.lastname: Draghiciu
authors.affiliation: Department of Medical Microbiology, Tumor Virology and Cancer Immunotherapy, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van de Wall
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Manuelli
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: R A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Gynecological Oncology, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Nijman
authors.affiliation: Department of Medical Microbiology, Tumor Virology and Cancer Immunotherapy, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Daemen
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands.
authors.forename: E F J
authors.initials: EF
authors.lastname: de Vries
keywords: 18[F]FB-IL-2; Activated T lymphocytes; PET; immunotherapy; interleukin-2; molecular imaging; radiation