SAFIR-I: Design and Performance of a High-Rate Preclinical PET Insert for MRI

(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.

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In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

Molecular Imaging ◽

10.2310/7290.2005.05133 ◽

2005 ◽

Vol 4 (4) ◽

pp. 7290.2005.05133 ◽

Cited By ~ 19

Author(s):

Matthew J. Hardwick ◽

Ming-Kai Chen ◽

Kwamena Baidoo ◽

Martin G. Pomper ◽

Tomás R. Guilarte

Keyword(s):

In Vivo Imaging ◽

Ex Vivo ◽

Inflammatory Diseases ◽

Imaging Techniques ◽

Benzodiazepine Receptors ◽

Small Animal ◽

Small Animal Pet ◽

Planar Imaging ◽

Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

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An in vivo multimodal feasibility study in a rat brain tumour model using flexible multinuclear MR and PET systems

10.21203/rs.3.rs-19775/v1 ◽

2020 ◽

Author(s):

Chang-Hoon Choi ◽

Carina Stegmayr ◽

Aliaksandra Shymanskaya ◽

Wieland A. Worthoff ◽

Nuno A da Silva ◽

...

Keyword(s):

Brain Tumour ◽

Small Animal ◽

Optimal Combination ◽

Small Animal Pet ◽

Molecular Profile ◽

Genetic Profile ◽

Normal Brain ◽

Valuable Insight ◽

Wide Range

Abstract Background : In addition to the structural information afforded by 1 H MRI, the use of X-nuclei, such as sodium-23 ( 23 Na) or phosphorus-31 ( 31 P), offers important complementary information concerning physiological and biochemical parameters. By then combining this technique with PET, which provides valuable insight into a wide range of metabolic and molecular processes by using of a variety of radioactive tracers, the scope of medical imaging and diagnostics can be significantly increased. While the use of multimodal imaging is undoubtedly advantageous, identifying the optimal combination of these parameters to diagnose a specific dysfunction is very important and is advanced by the use of sophisticated imaging techniques in specific animal models.Methods : In this pilot study, rats with intracerebral 9L gliosarcomas were used to explore a combination of sequential multinuclear MRI using a sophisticated switchable coil set in a small animal 9.4 T MRI scanner and, subsequently, a small animal PET with the tumour tracer O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ( 18 F-FET). This enabled in vivo multinuclear MR-PET experiments to be conducted without compromising the performance of either multinuclear MR or PET.Results : High-quality in vivo images and spectra including high-resolution 1 H imaging, 23 Na-weighted imaging, detection of 31 P metabolites and 18 F-FET uptake were obtained, allowing the characterisation of tumour tissues in comparison to a normal brain. These parameters have been shown to be useful in the identification of the genetic profile of gliomas, particularly concerning the mutation of the isocitrate hydrogenase gene, which is highly relevant for treatment strategy.Conclusions : The combination of multinuclear MR and PET in, for example, brain tumour models with specific genetic mutations will enable the physiological background of signal alterations to be explored and the identification of the optimal combination of imaging parameters for the non-invasive characterisation of the molecular profile of tumours.

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Coregistration of Small Animal PET and Autoradiography for in vivo–ex vivo Comparison

Lecture Notes in Computer Science - Progress in Pattern Recognition, Image Analysis and Applications ◽

10.1007/978-3-540-76725-1_85 ◽

2007 ◽

pp. 822-830

Author(s):

Soo-Min Song ◽

Min-Jeong Kim ◽

Joung-Min Lee ◽

Hye-Jin Park ◽

KyeongMin Kim ◽

...

Keyword(s):

Ex Vivo ◽

Small Animal ◽

Small Animal Pet ◽

Animal Pet

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New 55Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging

Pharmaceuticals ◽

10.3390/ph12040166 ◽

2019 ◽

Vol 12 (4) ◽

pp. 166 ◽

Cited By ~ 4

Author(s):

Lauren L. Radford ◽

Solana Fernandez ◽

Rebecca Beacham ◽

Retta El Sayed ◽

Renata Farkas ◽

...

Keyword(s):

Folate Receptor ◽

Small Animal ◽

Small Animal Pet ◽

Receptor Imaging ◽

Albumin Binding ◽

Liver Uptake ◽

Biodistribution Studies ◽

Positron Emission

Overexpression of folate receptors (FRs) on different tumor types (e.g., ovarian, lung) make FRs attractive in vivo targets for directed diagnostic/therapeutic agents. Currently, no diagnostic agent suitable for positron emission tomography (PET) has been adopted for clinical FR imaging. In this work, two 55Co-labeled albumin-binding folate derivatives-[55Co]Co-cm10 and [55Co]Co-rf42-with characteristics suitable for PET imaging have been developed and evaluated. High radiochemical yields (≥95%) and in vitro stabilities (≥93%) were achieved for both compounds, and cell assays demonstrated FR-mediated uptake. Both 55Co-labeled folate conjugates demonstrated high tumor uptake of 17% injected activity per gram of tissue (IA/g) at 4 h in biodistribution studies performed in KB tumor-bearing mice. Renal uptake was similar to other albumin-binding folate derivatives, and liver uptake was lower than that of previously reported [64Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors.

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Implementation of 89Zr production and in vivo imaging of B-cells in mice with 89Zr-labeled anti-B-cell antibodies by small animal PET/CT

Applied Radiation and Isotopes ◽

10.1016/j.apradiso.2011.02.040 ◽

2011 ◽

Vol 69 (6) ◽

pp. 852-857 ◽

Cited By ~ 26

Author(s):

Martin Walther ◽

Peter Gebhardt ◽

Philipp Grosse-Gehling ◽

Lydia Würbach ◽

Ingo Irmler ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

In Vivo Imaging ◽

Small Animal ◽

Small Animal Pet ◽

Animal Pet ◽

Pet Ct

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Effects of posture on regional pulmonary blood flow in rats as measured by PET

Journal of Applied Physiology ◽

10.1152/japplphysiol.91257.2008 ◽

2010 ◽

Vol 108 (2) ◽

pp. 422-429 ◽

Cited By ~ 11

Author(s):

Torsten Richter ◽

Ralf Bergmann ◽

Jens Pietzsch ◽

Inge Közle ◽

Frank Hofheinz ◽

...

Keyword(s):

Blood Flow ◽

Pulmonary Blood Flow ◽

Small Animal ◽

Vertical Gradient ◽

Human Albumin ◽

Small Animal Pet ◽

Longitudinal Measurements ◽

Spatial Differences ◽

Spontaneously Breathing

Using small animal PET with 68Ga-radiolabeled human albumin microspheres (Ga-68-microspheres), we investigated the effect of posture on regional pulmonary blood flow (PBF) in normal rats. This in vivo method is noninvasive and quantitative, and it allows for repeated longitudinal measurements. The purpose of the experiment was to quantify spatial differences in PBF in small animals in different postures. Two studies were performed in anesthetized, spontaneously breathing Wistar rats. Study 1 was designed to determine PBF in the prone and supine positions. Ga-68-microspheres were given to five prone and eight supine animals. We found that PBF increased in dorsal regions of supine animals (0.75) more than in prone animals (0.70; P = 0.037), according to a steeper vertical gradient of flow in supine than in prone animals. No differences in spatial heterogeneity were detected. Study 2 was designed to determine the effects of tissue distribution on PBF measurements. Because microspheres remained fixed in the lung, PET was performed on animals in the position in which they received Ga-68-microsphere injections and thereafter in the opposite posture. The distribution of PBF showed a preference for dorsal regions in both positions, but the distribution was dependent on the position during administration of the microspheres. We conclude that PET using Ga-68-microspheres can detect and quantify regional PBF in animals as small as the rat. PBF distributions differed between the prone and supine postures and were influenced by the distribution of lung tissue within the thorax.

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Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

10.20944/preprints202110.0231.v1 ◽

2021 ◽

Author(s):

Ruiqing Ni

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Animal Models ◽

Amyloid Beta ◽

High Field ◽

Diffusion Tensor ◽

Small Animal ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Mri

Amyloid-beta plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant amyloid-beta and tau accumulation induce neuroinflammation, cerebrovascular alterations, synaptic deficits, functional deficits, and neurodegeneration, leading to cognitive impairment. Animal models recapitulating the amyloid-beta pathology such as transgenic, knock-in mouse and rat models have facilitated the understanding of disease mechanisms and development of therapeutics targeting at amyloid-beta. There is a rapid advance in high-field MR in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences such as diffusion tensor imaging, arterial spin labelling, resting-state functional MRI, anatomical MRI, MR spectroscopy as well as contrast agents have been developed for the applications in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole brain field-of-view. MRI have been utilized to visualize non-invasively the amyloid-beta deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, cerebrovascular and glymphatic system in animal models of amyloidosis. Many of the readouts are translational in clinical MRI in the brain of patients with Alzheimer’s disease. In this review, we summarize the recent advance of using MRI for visualizing the pathophysiology in amyloidosis animal model. We discuss the outstanding challenges in brain imaging using MRI in small animal and propose future outlook in visualizing amyloid-beta-related alterations in brain of animal models.

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Radiosynthesis and Evaluation of Cyclohexyl (5-(2-[11C-Carbonyl]acetamidobenzo[d]thiazol-6-yl)-2-Methylpyridin-3-yl)Carbamate ([11C]PK68) As a New Radioligand For Imaging Receptor-Interacting Protein 1 Kinase

10.21203/rs.3.rs-1201743/v1 ◽

2022 ◽

Author(s):

Tomoteru Yamasaki ◽

Katsushi Kumata ◽

Atsuto Hiraishi ◽

Yiding Zhang ◽

Hidekatsu Wakizaka ◽

...

Keyword(s):

Acetyl Chloride ◽

Radiochemical Purity ◽

Specific Binding ◽

Small Animal ◽

Small Animal Pet ◽

Interacting Protein ◽

Molar Activity ◽

Positron Emission ◽

Key Enzyme

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.

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A Semi Rigid Novel Hydroxamate AMPED-Based Ligand for 89Zr PET Imaging

Molecules ◽

10.3390/molecules26195819 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5819

Author(s):

Lisa Russelli ◽

Francesco De Rose ◽

Loredana Leone ◽

Sybille Reder ◽

Markus Schwaiger ◽

...

Keyword(s):

Pet Imaging ◽

Ex Vivo ◽

Small Animal ◽

Biologically Active ◽

Small Animal Pet ◽

Organ Distribution ◽

Complexing Agent ◽

Distribution Studies

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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