Key result
In an in vivo study using A549-based tumor-bearing mice, the 18F-labeled senicapoc derivative successfully delineated the tumor signal with a tumor-to-muscle ratio of 1.47 ± 0.24.
Why the study?
K Ca 3.1 is overexpressed in many tumor entities and predicts disease progression, but in vivo PET imaging using a selective radiotracer needed to be established.
The 18F-labeled derivative of senicapoc shows promise as a PET tracer for in vivo imaging of the K Ca 3.1 channel, demonstrating stability and a tumor-to-muscle ratio of 1.47 in a mouse model.
May support KCa3.1-targeted PET tracer development; hypothesis-generating for human tumor imaging.
The calcium‐activated potassium channel 3.1 (K Ca 3.1) is overexpressed in many tumor entities and has predictive power concerning disease progression and outcome. Imaging of the K Ca 3.1 channel in vivo using a radiotracer for positron emission tomography (PET) could therefore establish a potentially powerful diagnostic tool. Senicapoc shows high affinity and excellent selectivity toward the K Ca 3.1 channel. We have successfully pursued the synthesis of the 18 F‐labeled derivative [ 18 F] 3 of senicapoc using the prosthetic group approach with 1‐azido‐2‐[ 18 F]fluoroethane ([ 18 F] 6 ) in a “click” reaction. The biological activity of the new PET tracer was evaluated in vitro and in vivo. Inhibition of the K Ca 3.1 channel by 3 was demonstrated by patch clamp experiments and the binding pose was analyzed by docking studies. In mouse and human serum, [ 18 F] 3 was stable for at least one half‐life of [ 18 F]fluorine. Biodistribution experiments in wild‐type mice were promising, showing rapid and predominantly renal excretion. An in vivo study using A549‐based tumor‐bearing mice was performed. The tumor signal could be delineated and image analysis showed a tumor‐to‐muscle ratio of 1.47 ± 0.24. The approach using 1‐azido‐2‐[ 18 F]fluoroethane seems to be a good general strategy to achieve triarylacetamide‐based fluorinated PET tracers for imaging of the K Ca 3.1 channel in vivo.
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Konken et al. (2022) studied Tumor. 18F-labeled derivative [18F]3 of senicapoc was evaluated on Tumor-to-muscle ratio. In an in vivo study using A549-based tumor-bearing mice, the 18F-labeled senicapoc derivative successfully delineated the tumor signal with a tumor-to-muscle ratio of 1.47 ± 0.24.
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