scholarly journals Alpha-Synuclein PET Tracer Development—An Overview about Current Efforts

2021 ◽  
Vol 14 (9) ◽  
pp. 847 ◽  
Author(s):  
Špela Korat ◽  
Natasha Shalina Rajani Bidesi ◽  
Federica Bonanno ◽  
Adriana Di Nanni ◽  
Anh Nguyên Nhât Hoàng ◽  
...  
Keyword(s):  
Alpha Synuclein ◽  
Postmortem Brain ◽  
Comprehensive Overview ◽  
Pet Tracers ◽  
Ligand Selectivity ◽  
Affinity Ligand ◽  
Pet Tracer ◽  
Positron Emission ◽  
Postmortem Brain Tissue

Neurodegenerative diseases such as Parkinson’s disease (PD) are manifested by inclusion bodies of alpha-synuclein (α-syn) also called α-synucleinopathies. Detection of these inclusions is thus far only possible by histological examination of postmortem brain tissue. The possibility of non-invasively detecting α-syn will therefore provide valuable insights into the disease progression of α-synucleinopathies. In particular, α-syn imaging can quantify changes in monomeric, oligomeric, and fibrillic α-syn over time and improve early diagnosis of various α-synucleinopathies or monitor treatment progress. Positron emission tomography (PET) is a non-invasive in vivo imaging technique that can quantify target expression and drug occupancies when a suitable tracer exists. As such, novel α-syn PET tracers are highly sought after. The development of an α-syn PET tracer faces several challenges. For example, the low abundance of α-syn within the brain necessitates the development of a high-affinity ligand. Moreover, α-syn depositions are, in contrast to amyloid proteins, predominantly localized intracellularly, limiting their accessibility. Furthermore, another challenge is the ligand selectivity over structurally similar amyloids such as amyloid-beta or tau, which are often co-localized with α-syn pathology. The lack of a defined crystal structure of α-syn has also hindered rational drug and tracer design efforts. Our objective for this review is to provide a comprehensive overview of current efforts in the development of selective α-syn PET tracers.

scholarly journals Multiple PET tracers for use in the classification of gliomas according to the 2016 WHO criteria

2020 ◽  
Author(s):  
Keisuke Miyake ◽  
Kenta Suzuki ◽  
Tomoya B Ogawa ◽  
Daisuke Ogawa ◽  
Tetsuhiro Hatakeyama ◽  
...  
Keyword(s):  
Who Classification ◽  
Standardized Uptake Value ◽  
Metabolic Tumor Volume ◽  
Who Criteria ◽  
Pet Tracers ◽  
Pet Tracer ◽  
Positron Emission ◽  
18F Fdg ◽  
Classification Of Gliomas

Abstract Background The molecular diagnosis of gliomas such as isocitrate dehydrogenase (IDH) status (wild-type [wt] or mutation [mut]) is especially important in the 2016 WHO classification. Positron emission tomography (PET) has afforded molecular and metabolic diagnostic imaging. The present study aimed to define the interrelationship between the 2016 WHO classification of gliomas and the integrated data from PET images using multiple tracers, including 18F-fluorodeoxyglucose ( 18F-FDG), 11C-methionine ( 11C-MET), 18F-fluorothymidine ( 18F-FLT), and 18F-fluoromisonidazole ( 18F-FMISO). Methods This retrospective, single-center study comprised 113 patients with newly diagnosed glioma based on the 2016 WHO criteria. Patients were divided into four glioma subtypes (Mut, Codel, Wt, and glioblastoma multiforme [GBM]). Tumor standardized uptake value (SUV) divided by mean normal cortical SUV (tumor-normal tissue ratio [TNR]) was calculated for 18F-FDG, 11C-MET, and 18F-FLT. Tumor-blood SUV ratio (TBR) was calculated for 18F-FMISO. To assess the diagnostic accuracy of PET tracers in distinguishing glioma subtypes, a comparative analysis of TNRs and TBR as well as the metabolic tumor volume (MTV) were calculated by Scheffe’s multiple comparison procedure for each PET tracer following the Kruskal–Wallis test. Results The differences in mean 18F-FLT TNR and 18F-FMISO TBR were significant between GBM and other glioma subtypes (p < 0.001). Regarding the comparison between Gd-T1WI volumes and 18F-FLT MTVs or 18F-FMISO MTVs, we identified significant differences between Wt and Mut or Codel (p < 0.01). Conclusion Combined administration of four PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.

scholarly journals 11C-Labeled Pictilisib (GDC-0941) as a Molecular Tracer Targeting Phosphatidylinositol 3-Kinase (PI3K) for Breast Cancer Imaging

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Na Han ◽  
Yaqun Jiang ◽  
Yongkang Gai ◽  
Qingyao Liu ◽  
Lujie Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pik3ca Mutation ◽  
Phosphatidylinositol 3 Kinase ◽  
Pet Tracer ◽  
Positron Emission ◽  
Pet Scans ◽  
Mcf 7 ◽  
Phosphatidylinositol 3

Pictilisib (GDC-0941) is an inhibitor of phosphatidylinositol 3-kinase (PI3K), part of a signaling cascade involved in breast cancer development. The purpose of this study was to evaluate the pharmacokinetics of pictilisib noninvasively by radiolabeling it with 11C and to assess the usability of the resulting [11C]-pictilisib as a positron-emission tomography (PET) tracer to screen for pictilisib-sensitive tumors. In this study, pictilisib was radiolabeled with [11C]-methyl iodide to obtain 11C-methylated pictilisib ([11C]-pictilisib) using an automated synthesis module with a high radiolabeling yield. Considerably higher uptake ratios were observed in MCF-7 (PIK3CA mutation, pictilisib-sensitive) cells than those in MDA-MB-231 (PIK3CA wild-type, pictilisib-insensitive) cells at all evaluated time points, indicating good in vitro binding of [11C]-pictilisib. Dynamic micro-PET scans in mice and biodistribution results showed that [11C]-pictilisib was mainly excreted via the hepatobiliary tract into the intestines. MCF-7 xenografts could be clearly visualized on the static micro-PET scans, while MDA-MB-231 tumors could not. Biodistribution results of two xenograft models showed significantly higher uptake and tumor-to-muscle ratios in the MCF-7 xenografts than those in MDA-MB-231 xenografts, exhibiting high in vivo targeting specificity. In conclusion, [11C]-pictilisib was first successfully prepared, and it exhibited good potential to identify pictilisib-sensitive tumors noninvasively, which may have a great impact in the treatment of cancers with an overactive PI3K/Akt/mTOR signal pathway. However, the high activity in hepatobiliary system and intestines needs to be addressed.

scholarly journals Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue

2015 ◽  
Vol 78 (5) ◽  
pp. 787-800 ◽  
Author(s):  
Marta Marquié ◽  
Marc D. Normandin ◽  
Charles R. Vanderburg ◽  
Isabel M. Costantino ◽  
Elizabeth A. Bien ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tissue ◽  
Emission Tomography ◽  
Postmortem Brain ◽  
Positron Emission Tomography Tracer ◽  
Positron Emission ◽  
Postmortem Brain Tissue

scholarly journals Quantification of [11C]PIB PET for Imaging Myelin in the Human Brain: A Test—Retest Reproducibility Study in High-Resolution Research Tomography

2015 ◽  
Vol 35 (11) ◽  
pp. 1771-1782 ◽  
Author(s):  
Mattia Veronese ◽  
Benedetta Bodini ◽  
Daniel García-Lorenzo ◽  
Marco Battaglini ◽  
Salvatore Bongarzone ◽  
...  
Keyword(s):  
High Resolution ◽  
High Reliability ◽  
Intraclass Correlation ◽  
Volume Ratio ◽  
Reference Region ◽  
Brain White Matter ◽  
Reproducibility Study ◽  
Pet Tracer ◽  
Positron Emission

An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [11C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [11C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test–retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [11C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers < 1%) and reproducibility (intraclass correlation coefficient (ICC) > 0.95). [11C]PIB parametric maps were also found to be significantly correlated ( R2 > 0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [11C]PIB imaging and nonmyelin-associated proteins.

scholarly journals [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor

2007 ◽  
Vol 104 (23) ◽  
pp. 9800-9805 ◽  
Author(s):  
H. D. Burns ◽  
K. Van Laere ◽  
S. Sanabria-Bohorquez ◽  
T. G. Hamill ◽  
G. Bormans ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Imaging ◽  
Emission Tomography ◽  
Cannabinoid 1 Receptor ◽  
Pet Tracer ◽  
Positron Emission

scholarly journals A 11C-Labeled 1,4-Dihydroquinoline Derivative as a Potential PET Tracer for Imaging of Redox Status in Mouse Brain

2015 ◽  
Vol 35 (12) ◽  
pp. 1930-1936 ◽  
Author(s):  
Toshimitsu Okamura ◽  
Maki Okada ◽  
Tatsuya Kikuchi ◽  
Hidekatsu Wakizaka ◽  
Ming-Rong Zhang
Keyword(s):  
Mouse Brain ◽  
Initial Velocity ◽  
Brain Homogenate ◽  
Redox Balance ◽  
Redox Status ◽  
Cationic Form ◽  
Pet Tracer ◽  
Positron Emission ◽  
The Brain

A disturbance in redox balance has been implicated in the pathogenesis of a number of diseases. This study sought to examine the feasibility of imaging brain redox status using a 11C-labeled dihydroquinoline derivative ([11C]DHQ1) for positron emission tomography (PET). The lipophilic PET tracer [11C]DHQ1 was rapidly oxidized to its hydrophilic form in mouse brain homogenate. The redox modulators diphenyleneiodonium and apocynin significantly reduced the initial velocity of [11C]DHQ1 oxidation, and apocynin also caused concentration-dependent inhibition of the initial velocity. Moreover, [11C]DHQ1 readily entered the brain by diffusion after administration and underwent oxidation into the hydrophilic cationic form, which then slowly decreased. By contrast, apocynin treatment inhibited the in vivo oxidation of [11C]DHQ1 to the hydrophilic cationic form, leading to a rapid decrease of radioactivity in the brain. Thus, the difference in the [11C]DHQ1 kinetics reflects the alteration in redox status caused by apocynin. In conclusion, [11C]DHQ1 is a potential PET tracer for imaging of redox status in the living brain.

scholarly journals STMO-5 Utilization of intraoperative multimodal technologies [PET and 5-ALA] for treating glioblastoma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi12-vi12
Author(s):  
Keisuke Miyake ◽  
Daisuke Ogawa ◽  
Tetsuhiro Hatakeyama
Keyword(s):  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Residual Tumor ◽  
Tau Proteins ◽  
Tumor Removal ◽  
Removal Rates ◽  
Pet Tracers ◽  
Pet Tracer ◽  
Positron Emission ◽  
Pet Scans

Abstract Background: We can improve prognosis of glioblastoma by using positron emission tomography (PET) scans to guide them in removing tumors, and intraoperative magnetic resonance imaging (IoMRI) and 5-aminolevulinic acid (5-ALA) for identifying residual tumors. Tau proteins are reported to accumulate in glioblastomas, so we compared the efficacy of their PET tracer, THK5351, against that of 11C-MET, 18F-FLT, and 18F-FMISO. Methods: Patients (n = 11) underwent scans between February 2020 and July 2021 for glioblastoma resection. Tumor-to-normal tissue accumulation ratio (TNR) and accumulation volumes of 4 PET tracers were evaluated. Following excisions, 5-ALA fluorescent evaluation was classified as strong, vague, or none. Residual tumor volumes and removal rates were determined using T1Gd assessments and PET tracers. IoMRI confirmed presence of residual tumors.Results: THK5351 had a TNR of 5.20, and its accumulated volume was greater than that of other tracers: 1.80 for 11C-MET, 1.72 for 18F-FLT, and 2.82 for 18F-FMISO. 5-ALA fluorescent evaluation was vague (n = 7) or none (n = 4); respective residual tumor volumes (mL) were 2.3 and 0.2 (T1Gd), 5.7 and 0.9 (11C-MET), 5.6 and 0.6 (18F-FLT), 1.3 and 0.4 (18F-FMISO), and 7 and 1.4 (THK5351); respective tumor removal rates (%) were 90.4 and 99.6 (T1Gd), 79.2 and 86.4 (11C-MET), 84.4 and 89.2 (18F-FLT), 94.3 and 94.4 (18F-FMISO), and 72.3 and 83.4 (THK5351). The excised tumor tissue was found in the area where only THK5351 was accumulated.Conclusions: THK5351 accumulated in glioblastomas to a greater degree than that of other tracers, making it useful for discriminating between healthy and malignant tissues.

scholarly journals Neuroimaging with Radiopharmaceuticals Targeting the Glutamatergic System

2020 ◽  
Vol 74 (12) ◽  
pp. 960-967
Author(s):  
Linjing Mu ◽  
Stefanie D. Krämer ◽  
Hazem Ahmed ◽  
Stefan Gruber ◽  
Susanne Geistlich ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Tumor Imaging ◽  
Human Subjects ◽  
Receptor Subtype ◽  
Imaging Data ◽  
Glutamatergic System ◽  
Pet Tracers ◽  
Pet Tracer ◽  
Positron Emission

Radiopharmacy at ETH has worked on the development of novel PET tracers for neuro-, cardiac- and tumor imaging for many years. In this paper, our efforts on targeting the glutamatergic system of the metabotropic glutamate receptor subtype 5 (mGluR5) and the ionotropic N-methyl-<small>D</small>-aspartate (NMDA) receptor are summarized. We briefly described the principles of positron emission tomography (PET) tracer development for the central nervous system (CNS) and the radiolabeling methods used in our laboratory. To assess the radioligands, results of in vitro autoradiography, biodistribution, and metabolite studies as well as PET imaging data are discussed. Furthermore, key PET parameters for kinetic modeling and quantification methods are provided. Two mGluR5 PET tracers, [11C]ABP688 and [18F]PSS232, were translated in our GMP labs and evaluated in human subjects. The newly developed GluN2B PET tracer [11C]Me-NB1 is currently being investigated in a first-in-human PET study and several F-18 labeled tracers are being evaluated in non-human primates in which the first-in-class will be translated for human studies.

scholarly journals Synthesis and Preclinical Evaluation of [18F]PF04217903, a Selective MET PET Tracer

2020 ◽  
Author(s):  
Vegard Torp Lien ◽  
Emily Hauge ◽  
Syed Nuruddin ◽  
Jo Klaveness ◽  
Dag Erlend Olberg
Keyword(s):  
Growth Factor Receptor ◽  
Radiochemical Yield ◽  
Molar Activity ◽  
Bioisosteric Replacement ◽  
Pet Tracer ◽  
Positron Emission ◽  
Wide Range ◽  
Hepatocyte Growth

<p>The tyrosine kinase MET (hepatocyte growth factor receptor) is abnormally activated in a wide range of cancers and is often correlated with a poor prognosis. Precision medicine with positron emission tomography (PET) can potentially aid in the assessment of tumor biochemistry and heterogeneity, which can prompt the selection of the most effective therapeutic regimes. The selective MET inhibitor PF04217903 (<b>1</b>) formed the basis for a bioisosteric replacement to the deoxyfluorinated analogue [<sup>18</sup>F]<b>2</b>, intended as a PET tracer for MET. [<sup>18</sup>F]<b>2 </b>could be synthesized with a “hydrous fluoroethylation” protocol in 6.3 ± 2.6% radiochemical yield and a molar activity of >50 GBq/µmol. <i>In vitro</i> autoradiography indicated that [<sup>18</sup>F]<b>2 </b>specifically binds to MET in PC3 tumor tissue, and <i>in vivo</i> biodistribution in mice showed predominantly a hepatobiliary excretion along with a low retention of radiotracer in other organs. </p>

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