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2022 ◽  
Author(s):  
Tomoteru Yamasaki ◽  
Katsushi Kumata ◽  
Atsuto Hiraishi ◽  
Yiding Zhang ◽  
Hidekatsu Wakizaka ◽  
...  

Abstract Background: Receptor-interacting protein 1 kinase (RIPK1) is a key enzyme in the regulation of cellular necroptosis. Recently, cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate (PK68, 5) has been developed as a potent inhibitor of RIPK1. Herein, we radiosynthesized [11C]PK68 as a new positron emission tomography (PET) ligand for imaging RIPK1 and evaluated its potential in vivo.Results: We synthesized [11C]PK68 by reacting amine precursor 14 with [11C]acetyl chloride. At the end of synthesis, we obtained [11C]PK68 of 1200–1790 MBq (n = 10) with >99% radiochemical purity and a molar activity of 37–99 GBq/μmol starting from 18–33 GBq of [11C]CO2. The fully automated synthesis took 30 min from the end of irradiation. In a small-animal PET study, [11C]PK68 was rapidly distributed in the liver and kidneys of healthy mice after injection, and was subsequently cleared from their bodies via hepatobiliary excretion and the intestinal reuptake pathway. Although there was no obvious specific binding of RIPK1 in the PET study, [11C]PK68 demonstrated relatively high stability in vivo, and may be used as a lead compound for further candidate development.Conclusions: In the present study, we successfully radiosynthesized [11C]PK68 and evaluated its potential in vivo. We are planning to optimize the chemical structure of [11C]PK68 and conduct further PET studies on it using pathological models.


Crystals ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Xi Zhang ◽  
Xin Yu ◽  
Zhiliang Zhu ◽  
Hongsen Yu ◽  
Heng Zhang ◽  
...  

Dual-layer-offset or multi-layer-offset design of a PET detector can improve spatial resolution while maintaining high sensitivity. In this study, three dual-layer-offset LYSO detectors with three different reflectors (ESR, Toray, and BaSO4) were developed. The top layer consisted of a 17 × 17 array of crystals 1 × 1 × 6.5 mm3 in size and the bottom layer consisted of an 18 × 18 array of crystals 1 × 1 × 9.5 mm3 in size. Neither light guides nor optical glue were used between the two layers of crystals. A custom-designed electronics system, composed of a 6 × 6 SiPM array, two FPC cables, and a custom-designed data processing module, was used to read out signals. An optimized interaction-decoding algorithm using the center of gravity to determine the position and threshold of analog signals for timing methods was applied to generate decoding flood histograms. The detector performances, in terms of peak to valley ratio of the flood histograms and energy resolutions, were calculated and compared. The dual-layer-offset PET detector constructed with BaSO4 reflectors performed much better than the other two reflectors in both crystal identification and energy resolution. The average peak-to-valley ratio and the energy resolution were approximately 7 and 11%, respectively. In addition, the crystals in the bottom layer showed better performance at crystal identification than those in the top layer. This study can act as a reference providing guidance in choosing scintillator reflectors for multi-layer dedicated DOI detectors designed for small-animal PET imaging.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Christoph Eissler ◽  
Rudolf A. Werner ◽  
Paula Arias-Loza ◽  
Naoko Nose ◽  
Xinyu Chen ◽  
...  

Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. 18F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 ± 57.7 μl ∗ , 380.8 ± 57.2 μl ∗ , 398.0 ± 63.1 μl ∗ , and 444.8 ± 75.3 μl at 4, 8, 12, and 16 frames, respectively; ∗ P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed ( P < 0.005 ), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.


Author(s):  
Ryota Imura ◽  
Atsuko Nakanishi Ozeki ◽  
Nanako Shida ◽  
Mika Kobayashi ◽  
Hiroyuki Ida ◽  
...  

Sensors ◽  
2021 ◽  
Vol 21 (21) ◽  
pp. 7037
Author(s):  
Pascal Bebié ◽  
Robert Becker ◽  
Volker Commichau ◽  
Jan Debus ◽  
Günther Dissertori ◽  
...  

(1) Background: Small Animal Fast Insert for MRI detector I (SAFIR-I) is a preclinical Positron Emission Tomography (PET) insert for the Bruker BioSpec 70/30 Ultra Shield Refrigerated (USR) preclinical 7T Magnetic Resonance Imaging (MRI) system. It is designed explicitly for high-rate kinetic studies in mice and rats with injected activities reaching 500MBq, enabling truly simultaneous quantitative PET and Magnetic Resonance (MR) imaging with time frames of a few seconds in length. (2) Methods: SAFIR-I has an axial field of view of 54.2mm and an inner diameter of 114mm. It employs Lutetium Yttrium OxyorthoSilicate (LYSO) crystals and Multi Pixel Photon Counter (MPPC) arrays. The Position-Energy-Timing Application Specific Integrated Circuit, version 6, Single Ended (PETA6SE) digitizes the MPPC signals and provides time stamps and energy information. (3) Results: SAFIR-I is MR-compatible. The system’s Coincidence Resolving Time (CRT) and energy resolution are between separate-uncertainty 209.0(3)ps and separate-uncertainty 12.41(02) Full Width at Half Maximum (FWHM) at low activity and separate-uncertainty 326.89(12)ps and separate-uncertainty 20.630(011) FWHM at 550MBq, respectively. The peak sensitivity is ∼1.6. The excellent performance facilitated the successful execution of first in vivo rat studies beyond 300MBq. Based on features visible in the acquired images, we estimate the spatial resolution to be ∼2mm in the center of the Field Of View (FOV). (4) Conclusion: The SAFIR-I PET insert provides excellent performance, permitting simultaneous in vivo small animal PET/MR image acquisitions with time frames of a few seconds in length at activities of up to 500MBq.


Author(s):  
Jitao Li ◽  
Yuwen Wang ◽  
Yue Yang ◽  
Xin Zhang ◽  
Zongjin Qu ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Maxwell W. G. Miner ◽  
Heidi Liljenbäck ◽  
Jenni Virta ◽  
Semi Helin ◽  
Olli Eskola ◽  
...  

PurposeThe three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[18F]Fluoroglutamine ([18F]FGln), L-[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison.ProceduresUp to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models.ResultsAverage BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p &gt; 0.25).ConclusionsIn orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5819
Author(s):  
Lisa Russelli ◽  
Francesco De Rose ◽  
Loredana Leone ◽  
Sybille Reder ◽  
Markus Schwaiger ◽  
...  

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.


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