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

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.

Cousins at work: How combining medical with optical imaging enhances in vivo cell tracking

“…In contrast, radionuclide imaging (PET, SPECT) offers best depth penetration and absolute quantification ( Lajtos et al, 2014 ) with preclinical resolutions ≤1 mm ( Deleye et al, 2013 ; Nagy et al, 2013 ), but radionuclide imaging is more complex to perform and cell detection sensitivities are highly reporter-dependent and cell-specific. Cellular detection sensitivities have been reported to be as good as hundreds/thousands for cancer cells using NIS together with its PET and SPECT radiotracers, respectively, ( Diocou et al, 2017 ; Fruhwirth et al, 2014 ) and tens of thousands for smaller T-cells using various different reporters in preclinical experiments ( Moroz et al, 2015 ). As PET-CT/MRI and SPECT-CT/MRI instruments are nowadays preclinical and clinical standard, these multimodal approaches offer high sensitivities via PET or SPECT combined with CT or MRI, which add anatomical reference at higher resolution than radionuclide imaging techniques ( Fig.…”

Advanced Cancer Imaging Applied in the Comparative Setting

“…Access to such patients supports multiparametric imaging studies in a tractable period of time within their clinical management. Other examples of novel tracer development and application by inclusion of companion species include 13-C pyruvate magnetic resonance spectroscopy (21), and 18 F-tetrafluoroborate ( 18 F-BF − 4 or 18 F-TFB) for expressed sodium-iodide symporter (NIS) PET imaging (Figure 4), which could be a useful tool for clinical thyroid and neuroendocrine tumor imaging, for preclinical imaging of NIS-expressing disease models and for cell trafficking studies (22)(23)(24). We have also explored the utility of an 18 F-radiolabeled fatty acid 18 F-fluoro-thia-heptadecandoic acid for metabolic imaging of fatty acid oxidation, which is an emerging field in the study of cancer metabolism (Figure 5) (25,26).…”

“…As another example, one could envision the inclusion of companion dogs with cancer to bridge early investigations of dendritic cell migration in rodents using the novel PET probe 18 F-tetrafluoroborate that was mentioned above (22)(23)(24).…”

Rapid Aqueous Late‐Stage Radiolabelling of [GaF3(BnMe2‐tacn)] by 18F/19F Isotopic Exchange: Towards New PET Imaging Probes

“…Typically, radiofluorination is achieved by either converting a boronic ester moiety into a fluoroborate species or by an isotopic exchange reaction. Very recently, the development of [ 18 F]BF 4 − and [ 18 F]CF 3 SO 3 − as PET probes for imaging the sodium iodide symporter has been reported …”