In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates
COX-2 selective inhibitors (COXIBs) are non-steroidal anti-inflammatory drugs (NSAIDs), with fewer side effects compared with non-selective NSAIDs, and are used for the treatment of arthritis, headaches, and other inflammatory diseases of the brain and peripheral tissues. Radiolabeled COXIBs may per...
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doaj-4e1284494a2f40bc989e1db046d513f82020-11-24T21:17:19ZengMDPI AGMolecules1420-30492018-08-01238192910.3390/molecules23081929molecules23081929In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman PrimatesJ. S. Dileep Kumar0Bing Bai1Francesca Zanderigo2Christine DeLorenzo3Jaya Prabhakaran4Ramin V. Parsey5J. John Mann6Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USANow at Department of Radiology, University of Southern California, Los Angeles, CA 90089, USAMolecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USANow at Department of Psychiatry, Stony Brook School of Medicine, Stony Brook, New York, NY 11794, USAMolecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USANow at Department of Psychiatry, Stony Brook School of Medicine, Stony Brook, New York, NY 11794, USAMolecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USACOX-2 selective inhibitors (COXIBs) are non-steroidal anti-inflammatory drugs (NSAIDs), with fewer side effects compared with non-selective NSAIDs, and are used for the treatment of arthritis, headaches, and other inflammatory diseases of the brain and peripheral tissues. Radiolabeled COXIBs may permit positron emission tomography (PET) imaging of COX-2 localization and activity in diseases, enable monitoring of inflammatory processes, and determine target occupancy of COX-2 activity by NSAIDs, thus, accelerating the development of novel CIXIBs. We synthesized [11C]celecoxib, one of the COXIBs and a prescription drug, and here report its in vivo uptake in the brain, whole body biodistribution, and radiation dosimetry in baboons using PET. Brain imaging experiments were performed in one baboon and whole body PET scans were performed in triplicates in two male baboons using an ECAT ACCEL (Siemens Medical Solutions, Inc. Knoxville) under anesthetic conditions. PET studies in baboons show that [11C]celecoxib penetrates the blood brain barrier (BBB) and accumulates in the brain, followed by a washout of radioactivity. The liver has the highest residence time and the gallbladder is the critical organ for [11C]celecoxib. Organ Level Internal Dose Assessment (OLINDA) estimates indicate that the maximum permissible single study dosage of [11C]celecoxib in humans is 1110 MBq (30 mCi) for both males and females under the 21 CFR 361.1 dose limit for research subjects.http://www.mdpi.com/1420-3049/23/8/1929PETCOX-2celecoxibdosimetrybiodistributionbrain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
J. S. Dileep Kumar Bing Bai Francesca Zanderigo Christine DeLorenzo Jaya Prabhakaran Ramin V. Parsey J. John Mann |
spellingShingle |
J. S. Dileep Kumar Bing Bai Francesca Zanderigo Christine DeLorenzo Jaya Prabhakaran Ramin V. Parsey J. John Mann In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates Molecules PET COX-2 celecoxib dosimetry biodistribution brain |
author_facet |
J. S. Dileep Kumar Bing Bai Francesca Zanderigo Christine DeLorenzo Jaya Prabhakaran Ramin V. Parsey J. John Mann |
author_sort |
J. S. Dileep Kumar |
title |
In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates |
title_short |
In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates |
title_full |
In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates |
title_fullStr |
In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates |
title_full_unstemmed |
In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates |
title_sort |
in vivo brain imaging, biodistribution, and radiation dosimetry estimation of [11c]celecoxib, a cox-2 pet ligand, in nonhuman primates |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-08-01 |
description |
COX-2 selective inhibitors (COXIBs) are non-steroidal anti-inflammatory drugs (NSAIDs), with fewer side effects compared with non-selective NSAIDs, and are used for the treatment of arthritis, headaches, and other inflammatory diseases of the brain and peripheral tissues. Radiolabeled COXIBs may permit positron emission tomography (PET) imaging of COX-2 localization and activity in diseases, enable monitoring of inflammatory processes, and determine target occupancy of COX-2 activity by NSAIDs, thus, accelerating the development of novel CIXIBs. We synthesized [11C]celecoxib, one of the COXIBs and a prescription drug, and here report its in vivo uptake in the brain, whole body biodistribution, and radiation dosimetry in baboons using PET. Brain imaging experiments were performed in one baboon and whole body PET scans were performed in triplicates in two male baboons using an ECAT ACCEL (Siemens Medical Solutions, Inc. Knoxville) under anesthetic conditions. PET studies in baboons show that [11C]celecoxib penetrates the blood brain barrier (BBB) and accumulates in the brain, followed by a washout of radioactivity. The liver has the highest residence time and the gallbladder is the critical organ for [11C]celecoxib. Organ Level Internal Dose Assessment (OLINDA) estimates indicate that the maximum permissible single study dosage of [11C]celecoxib in humans is 1110 MBq (30 mCi) for both males and females under the 21 CFR 361.1 dose limit for research subjects. |
topic |
PET COX-2 celecoxib dosimetry biodistribution brain |
url |
http://www.mdpi.com/1420-3049/23/8/1929 |
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