TY - JOUR T1 - Initial <em>in vivo</em> evaluation of [<sup>11</sup>C]MPC-6827, a microtubule imaging agent in transgenic mice model of amyotrophic lateral sclerosis JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 181 LP - 181 VL - 60 IS - supplement 1 AU - Kiran Kumar Solingapuram Sai AU - Carol Milligan AU - Shamyaa Anchana Rajagopal AU - Jaya Prabhakaran AU - J. John Mann AU - Akiva Mintz AU - DILEEP KUMAR Y1 - 2019/05/01 UR - http://jnm.snmjournals.org/content/60/supplement_1/181.abstract N2 - 181Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive, mostly adult onset neurodegenerative disorder belonging to the class of motor neuron disease (MND), causing muscle weakness, spasticity, paralysis and death. There is currently no cure or validated diagnostic tools available for ALS. Among the biomarkers of ALS, significant loss of microtubule, a cytoskeleton protein is reported in postmortem ALS brain. Pharmacological stabilization of the microtubule network offers an attractive therapeutic strategy in ALS. Therefore, a non-invasive measurement of neuro microtubules, using PET imaging would robustly help clinicians to understand the complex ALS biochemical changes, thus aiding in personalizing treatment strategies. In this study, we evaluated the in vivo efficacy of [11C]MPC6827, the first BBB penetrating microtubule PET radiotracer, to image microtubule in transgenic ALS mice model using microPET imaging. Methods: The radiochemical synthesis of [11C]MPC-6827 was automated on a GE-FX2MeI/FX2M radiochemistry module by alkylating the corresponding desmethyl-MPC-6827 with [11C]MeI in DMF using NaOH. MicroPET/CT imaging with [11C]MPC-6827 was performed in 3 month old ALS mice model of superoxide dismutase mutation (SOD1[asterisk]G93A). Dynamic 0-60 min microPET/CT scanning studies were performed in anesthetized SOD1[asterisk]G93A transgenic and wild type mice (n=3) using Trifoil PET/CT scanner. Time Activity Curves (TACs) were derived from the whole brain, sub brain regions, and cervical spinal cord in both the transgenic and wild type mice. Results: [11C]MPC-6827 was synthesized with high radiochemical purity (&gt;98%) and specific activity (1.8+0.5 Ci/µmol) in 40+5% radiochemical yield, decay corrected to EOS (n =15). MicroPET imaging in SOD1[asterisk]G93A transgenic and wild type mice demonstrated BBB penetration and retention in brain. Based on regions of interest (ROI) analysis, transgenic SOD1[asterisk]G93A mice showed approximately 2-fold lower brain and spinal cord uptake when compared to wildtype littermates. Additionally, whole brain and cervical spinal TACs were also low in SOD1[asterisk]G93A transgenic mice over the wild type ones Conclusions: Initial in vivo studies in SOD1[asterisk]G93A mice indicated lower binding of [11C]MPC-6827 in transgenic mice compared to wild types. Our initial evaluations suggest that [11C]MPC-6827 can be a potential radiotracer for imaging ALS and other neurodegenerative disorders in which alteration of microtubule is hypothesized. ER -