PT - JOURNAL ARTICLE AU - Turkman, Nashaat AU - Xu, Sulan AU - Huang, Chun-Han AU - Eyermann, Christopher AU - Salino, Julia AU - Khan, Palwasha TI - <strong>Improved radiosynthesis, in vitro and in vivo validation with [18F]-NT160, a probe for molecular imaging of the epigenetics of the central nervous system.</strong> DP - 2023 Jun 01 TA - Journal of Nuclear Medicine PG - P1564--P1564 VI - 64 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/64/supplement_1/P1564.short 4100 - http://jnm.snmjournals.org/content/64/supplement_1/P1564.full SO - J Nucl Med2023 Jun 01; 64 AB - P1564 Introduction: The class-IIa histone deacetylases (class-IIa HDACs) are key component of the epigenetic machinery and their dysregulation in the brain has been implicated in the human disorders of the central nervous system (CNS). However, in vivo tools for mapping the distribution (protein density) of class-IIa HDACs in the CNS are lacking. Our research provides molecular imaging probe as a powerful tool for non-invasive, repetitive, and quantitative in vivo imaging of the brain in its entirety thus allowing for a contrast view of the healthy brain vs disease state. We expect this work to have a major positive impact for early detection of brain disease and disorders such as Alzheimer’s and Huntington’s diseases, ischemic stroke, traumatic brain injuries, and cancer.Methods: radiosynthesis and molar activity of [18F]-NT160. We performed a series of in vitro and in vivo studies to validate [18F]-NT160 as a positron emission tomography (PET) imaging probe for class-IIa HDACs. We performed self-blocking studies with the non-radioactive NT160 and the extent of radiometabolism of [18F]-NT160 in the rat brain homogentates and plasma was determined at 60 minutes post injection using in radio-thin layer chromatography (R-TLC) and high-performance liquid chromatography (HPLC). Results: The utility of 4-hydroxy-TEMPO in the radiosynthesis of [18F]-NT160 led to a significant improvement in radiochemical yield and molar activity. PET imaging with [18F]-NT160 showed a high contrast among various regions of the brain with higher uptake was observed in the hippocampus, thalamus, brainstem and cortex and relatively lower uptake in the striatum and cerebellum. The brain uptake was reduced in vivo when comparing time–activity curves obtained from the tracer administered at the baseline with images obtained from the tracer co-admistered with 1.0 mg/kg of the non-radioactive which demonstrates that that the binding/occupancy of to class-IIa HDACs in vivo is specific and displaceableConclusions: In summary, we reported a 4-hydroxy-TEMPO assisted radiosynthesis of [18F]-NT160, a radioligand for molecular imaging of class-IIa HDACs, a key component of the epigenetic machinery. PET imaging studies with [a favorable profile for in vivo imaging and is useful CNS lead PET tracer. [18F]-NT160 displayed excellent pharmacokinetic and imaging characteristics: brain uptake is high in gray matter regions, leading to high-quality PET images; tissue kinetics are appropriate for an [18F]-tracer and specific binding for class-IIa HDAC is demonstrated by self-blockade in vivo and in vitro using autoradiography. Overall, our current studies with [18F]-NT160 will likely facilitate the development and clinical translation of class-IIa HDACs of the next generation of PET tracers for imaging and targeted therapy of cancer and the diseases of the central nervous system (CNS).