Evaluation of in-vivo and in-vitro binding property of a novel PET tracer for CSF1R imaging and comparison with two currently-used CSF1R-PET tracers

Background Colony-stimulating factor 1 receptor (CSF1R) is a promising imaging biomarker for neuroinflammation or tumor-associated macrophages. However, existing positron emission tomography (PET) tracers for CSF1R imaging commonly are suffering from limited specificity or sensitivity. Results We have performed ¹¹ C-labeled radiosynthesis of compound FJRD (3-((2-amino-5-(1-methyl-1 H -pyrazol-4-yl)pyridin-3-yl)ethynyl)- N -(4-methoxyphenyl)-4-methylbenzamide) with excellent affinity for CSF1R and evaluated its in - vivo and in - vitro binding properties. PET images of [ ¹¹ C]FJRD show low brain uptake and specific binding in the living organs except kidneys in the normal mice and rats. In - vitro autoradiographs show high-level specific binding in all investigated organs including brain, spleen, liver, kidneys and lungs when used self-blocking. Addition of cold CPPC partially blocked in - vitro [ ¹¹ C]FJRD binding in the various organs with blocking effects from 9 to 67%, and other two CSF1R inhibitors, GW2580 and BLZ945, showed minimal blocking effect, suggesting unignorable off-target binding in these organs. Meanwhile specific bindings of [ ¹¹ C]CPPC and [ ¹¹ C]GW2580 were faint in the mouse organs except [ ¹¹ C]CPPC specific binding detectable in the spleen. Conclusions These results suggest [ ¹¹ C]FJRD as a potential CSF1R-PET tracer for more sensitively detecting CSF1R compared to [ ¹¹ C]CPPC and [ ¹¹ C]GW2580. However, high-level off-target binding requires further improvement in specificity for CSF1R imaging.