18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model

S Diocou,P J Blower,T Ng,M Jauregui-Osoro,F Man,G O Fruhwirth,G E D Mullen,K Chuamsaamarkkee,M Boudjemeline,A Volpe

doi:10.1038/s41598-017-01044-4

Abstract

Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [18F]tetrafluoroborate ([18F]BF4−) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [18F]BF4− (PET/CT) was compared to the conventional tracer [123I]iodide (sequential SPECT/CT). We found that [18F]BF4− was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [18F]BF4−-PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [18F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [18F]BF4−-PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest.

Highlights

In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues
Use of radioiodine in the context of NIS reporter gene imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) is complicated by the fact that, as well as being a substrate of NIS, iodide is a substrate of the peroxidase machinery of thyroid hormone synthesis, leading to metabolic trapping
We successfully demonstrated the utility of the recently developed NIS radiotracer [18F]BF4− for tumor and metastasis imaging by PET in a preclinical model of breast cancer

Summary

Introduction

In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Use of radioiodine in the context of NIS reporter gene imaging with PET or SPECT is complicated by the fact that, as well as being a substrate of NIS, iodide is a substrate of the peroxidase machinery of thyroid hormone synthesis, leading to metabolic trapping. This trapping mechanism is an advantage in imaging normal thyroid function or response to thyroid ablation, but complicates reporter gene imaging because it increases thyroid uptake, making the tracer less available for uptake in the non-thyroidal target cells, which do not have this additional metabolic trapping machinery. It has the advantages of the functional analogy to 99mTcO4− 23–25, while incorporating the radionuclide 18F, which is readily available and has excellent PET imaging characteristics

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