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A comparative uptake study of multiplexed PET tracers in mice with turpentine-induced inflammation.

ABSTRACT: The potential value of multiplexed positron emission tomography (PET) tracers in mice with turpentine-induced inflammation was evaluated and compared with 2-[¹?F]fluoro-2-deoxy-D-glucose ([¹?F]FDG) for glucose metabolism imaging. These PET tracers included [¹?F]fluoromethylcholine ([¹?F]FCH) for choline metabolism imaging, (S-[¹¹C]methyl)-D-cysteine ([¹¹C]DMCYS) for amino acid metabolism imaging, [¹¹C]bis(zinc(II)-dipicolylamine) ([¹¹C]DPA-Zn²?) for apoptosis imaging, 2-(4-N-[¹¹C]-methylaminophenyl)-6-hydroxybenzothiazole ([¹¹C]PIB) for ? amyloid binding imaging, and [¹?F]fluoride (¹?F?) for bone metabolism imaging. In mice with turpentine-induced inflammation mice, the biodistribution of all the tracers mentioned above at 5, 15, 30, 45, and 60 min postinjection was determined. Also, the time-course curves of the tracer uptake ratios for inflammatory thigh muscle (IM) to normal uninflammatory thigh muscle (NM), IM to blood (BL), IM to brain (BR), and IM to liver (LI) were acquired, respectively. Moreover, PET imaging with the tracers within 60 min postinjection on a clinical PET/CT scanner was also conducted. [¹?F]FDG and ¹?F? showed relatively higher uptake ratios for IM to NM, IM to BL, IM to BR, and IM to LI than [¹?F]FCH, [¹¹C]DPA-Zn²?, [¹¹C]DMCYS and [¹¹C]PIB, which were highly consistent with the results delineated in PET images. The results demonstrate that ¹?F? seems to be a potential PET tracer for inflammation imaging. [¹?F]FCH and [¹¹C]DMCYS, with lower accumulation in inflammatory tissue than [¹?F]FDG, are not good PET tracers for inflammation imaging. As a promising inflammatory tracer, the chemical structure of [¹¹C]DPA-Zn²? needs to be further optimized.

SUBMITTER: Huang T

PROVIDER: S-EPMC6268432 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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A comparative uptake study of multiplexed PET tracers in mice with turpentine-induced inflammation.

Huang Tingting T Wang Hongliang H Tang Ganghua G Liang Xiang X Nie Dahong D Yi Chang C Wu Kening K

Molecules (Basel, Switzerland) 20121126 12

The potential value of multiplexed positron emission tomography (PET) tracers in mice with turpentine-induced inflammation was evaluated and compared with 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) for glucose metabolism imaging. These PET tracers included [¹⁸F]fluoromethylcholine ([¹⁸F]FCH) for choline metabolism imaging, (S-[¹¹C]methyl)-D-cysteine ([¹¹C]DMCYS) for amino acid metabolism imaging, [¹¹C]bis(zinc(II)-dipicolylamine) ([¹¹C]DPA-Zn²⁺) for apoptosis imaging, 2-(4-N-[¹¹C]-methylaminophe ...[more]

PMID: 23183886

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Project description:The aim of this study was to compare the binding properties of several tau positron emission tomography tracers-THK5117, THK5351, T807 (also known as AV1451; flortaucipir), and PBB3-head to head in the same human brain tissue.Binding assays were performed to compare the regional distribution of 3H-THK5117 and 3H-THK5351 in postmortem tissue from three Alzheimer's disease (AD) cases and three control subjects in frontal and temporal cortices as well as in the hippocampus. Competition binding assays between THK5351, THK5117, PBB3, and T807, as well as off-target binding of THK5117 and T807 toward monoamine oxidase B (MAO-B), were performed using binding assays in brain homogenates and autoradiography of three AD cases.Regional binding of 3H-THK5117 and 3H-THK5351 was similar, except in the temporal cortex, which showed higher 3H-THK5117 binding. Saturation studies demonstrated two binding sites for 3H-THK5351 (K d1?=?5.6 nM, Bmax?=?76 pmol/g; K d2?=?1 nM, Bmax?=?40 pmol/g). Competition studies in the hippocampus between 3H-THK5351 and unlabeled THK5351, THK5117, and T807 revealed super-high-affinity sites for all three tracers (THK5351 K i?=?0.1 pM; THK5117 K i?=?0.3 pM; T807 K i?=?0.2 pM) and an additional high-affinity site (THK5351 K i?=?16 nM; THK5117 K i?=?20 nM; T807 K i?=?78nM). 18F-T807, 11C-THK5351, and 11C-PBB3 autoradiography of large frozen sections from three AD brains showed similar regional binding for the three tracers, with lower binding intensity for 11C-PBB3. Unlabeled THK5351 and T807 displaced 11C-THK5351 to a similar extent and a lower extent, respectively, compared with 11C-PBB3. Competition with the MAO-B inhibitor 3H-L-deprenyl was observed for THK5117 and T807 in the hippocampus (THK5117 K i?=?286 nM; T807 K i?=?227 nM) and the putamen (THK5117 K i?=?148 nM; T807 K i?=?135 nM). 3H-THK5351 binding was displaced using autoradiography competition with unlabeled THK5351 and T807 in cortical areas by 70-80% and 60-77%, respectively, in the basal ganglia, whereas unlabeled deprenyl displaced 3H-THK5351 binding by 40% in the frontal cortex and 50% in the basal ganglia.THK5351, THK5117, and T807 seem to target similar binding sites, but with different affinities, whereas PBB3 seems to target its own binding site. Both THK5117 and T807 demonstrated off-target binding in the hippocampus and putamen with a ten times lower binding affinity to the MAO-B inhibitor deprenyl compared with 3H-THK5351.

Dataset Information

A comparative uptake study of multiplexed PET tracers in mice with turpentine-induced inflammation.

Publications

A comparative uptake study of multiplexed PET tracers in mice with turpentine-induced inflammation.

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