P3‐087: <i>IN VIVO</i> EVALUATIONS OF MICROTUBULE‐BASED PET RADIOTRACER, [<sup>11</sup>C]MPC‐6827 IN MURINE MODELS OF ALZHEIMER'S DISEASE

Sai, Kiran Kumar Solingapuram; Whitlow, Christopher T.; Kumar, JS Dileep; Craft, Suzanne; Mintz, Akiva; Macauley‐Rambach, Shannon

doi:10.1016/j.jalz.2019.06.3114

Cited by 2 publications

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“…Our laboratory recently reported the design, development, and in vivo evaluations of the first brain-penetrating microtubule-based PET radiotracer, [ 11 C]MPC-6827 (Figure 1) in rodents [27]. Microtubule-based PET imaging could provide a novel imaging biomarker platform with which to diagnose disease pathology early on, and we are currently working on evaluating the microtubule-based PET imaging properties of [ 11 C]MPC-6827 in murine models of AD [28]. To explore the translational potential of [ 11 C]MPC-6827, non-human primate (NHP) brain PET imaging was initially performed in two adult male rhesus monkeys [29], in which we demonstrated high uptake in the whole brain.…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

et al. 2020

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Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

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Section: Introductionmentioning

confidence: 99%

PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

et al. 2020

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“…Our mechanistic experiments demonstrated that [ 11 C]MPC-6827 selectively binds to destabilized MTs. We showed the high brain penetration, favorable pharmacokinetics, and excellent test–retest properties of [ 11 C]MPC-6827 in normal healthy nonhuman primates (NHPs). , On the basis of these encouraging preliminary studies of [ 11 C]MPC-6827 in rodents and NHPs, , we went on to evaluate its imaging potential in an established NHP model of AD.…”

Section: Introductionmentioning

confidence: 99%

Preliminary PET Imaging of Microtubule-Based PET Radioligand [¹¹C]MPC-6827 in a Nonhuman Primate Model of Alzheimer’s Disease

Bhoopal,

Gollapelli,

Damuka

et al. 2023

ACS Chem. Neurosci.

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The microtubule (MT) instability observed in Alzheimer’s disease (AD) is commonly attributed to hyperphosphorylation of the MT-associated protein, tau. In vivo PET imaging offers an opportunity to gain critical information about MT changes with the onset and development of AD and related dementia. We developed the first brain-penetrant MT PET ligand, [11C]MPC-6827, and evaluated its in vivo imaging utility in vervet monkeys. Consistent with our previous in vitro cell uptake and in vivo rodent imaging experiments, [11C]MPC-6827 uptake increased with MT destabilization. Radioactive uptake was inversely related to (cerebrospinal fluid) CSF Aβ42 levels and directly related to age in a nonhuman primate (NHP) model of AD. Additionally, in vitro autoradiography studies also corroborated PET imaging results. Here, we report the preliminary results of PET imaging with [11C]MPC-6827 in four female vervet monkeys with high or low CSF Aβ42 levels, which have been shown to correlate with the Aβ plaque burden, similar to humans.

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P3‐087: IN VIVO EVALUATIONS OF MICROTUBULE‐BASED PET RADIOTRACER, [¹¹C]MPC‐6827 IN MURINE MODELS OF ALZHEIMER'S DISEASE

Cited by 2 publications

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PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Preliminary PET Imaging of Microtubule-Based PET Radioligand [¹¹C]MPC-6827 in a Nonhuman Primate Model of Alzheimer’s Disease

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P3‐087: IN VIVO EVALUATIONS OF MICROTUBULE‐BASED PET RADIOTRACER, [11C]MPC‐6827 IN MURINE MODELS OF ALZHEIMER'S DISEASE

Cited by 2 publications

References 0 publications

PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Preliminary PET Imaging of Microtubule-Based PET Radioligand [11C]MPC-6827 in a Nonhuman Primate Model of Alzheimer’s Disease

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P3‐087: IN VIVO EVALUATIONS OF MICROTUBULE‐BASED PET RADIOTRACER, [¹¹C]MPC‐6827 IN MURINE MODELS OF ALZHEIMER'S DISEASE

Preliminary PET Imaging of Microtubule-Based PET Radioligand [¹¹C]MPC-6827 in a Nonhuman Primate Model of Alzheimer’s Disease