Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging

S V Hartimath; O Draghiciu; S van de Wall; V Manuelli; R A J O Dierckx; H W Nijman; T Daemen; E F J de Vries

doi:10.1080/2162402X.2016.1248014

Noninvasive monitoring of cancer therapy induced activated T cells using [¹⁸F]FB-IL-2 PET imaging

Oncoimmunology. 2016 Nov 18;6(1):e1248014. doi: 10.1080/2162402X.2016.1248014. eCollection 2017.

Authors

S V Hartimath¹, O Draghiciu², S van de Wall², V Manuelli¹, R A J O Dierckx¹, H W Nijman³, T Daemen², E F J de Vries¹

Affiliations

¹ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands.
² Department of Medical Microbiology, Tumor Virology and Cancer Immunotherapy, University of Groningen, University Medical Center Groningen, the Netherlands.
³ Department of Gynecological Oncology, University of Groningen, University Medical Center Groningen, the Netherlands.

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.

Keywords: 18[F]FB-IL-2; Activated T lymphocytes; PET; immunotherapy; interleukin-2; molecular imaging; radiation.

Publication types

Research Support, Non-U.S. Gov't