scholarly journals Revisiting dithiadiaza macrocyclic chelators for copper-64 PET imaging

2020 ◽  
Vol 49 (40) ◽  
pp. 14088-14098
Author(s):  
Sergey Shuvaev ◽  
Elizaveta A. Suturina ◽  
Nicholas J. Rotile ◽  
Andrei Astashkin ◽  
Christopher J. Ziegler ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Pet Tracer ◽  
Macrocyclic Chelator

Copper-64 complex with a new dithiadiaza macrocyclic chelator was evaluated as a PET tracer.

scholarly journals Dealing with PET radiometabolites

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Krishna Kanta Ghosh ◽  
Parasuraman Padmanabhan ◽  
Chang-Tong Yang ◽  
Sachin Mishra ◽  
Christer Halldin ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Distribution Patterns ◽  
The Body ◽  
Analysis Process ◽  
Pet Tracer ◽  
Positron Emission ◽  
Structural Identity ◽  
Available Technology ◽  
Living Organisms ◽  
Entire Amount

Abstract Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract

Positron Emission Tomography (PET) for Flow Measurement

2011 ◽  
Vol 301-303 ◽  
pp. 1316-1321 ◽  
Author(s):  
Arthur E. Ruggles ◽  
Bi Yao Zhang ◽  
Spero M. Peters
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Three Dimensional ◽  
Bulk Water ◽  
Emission Tomography ◽  
Optical Methods ◽  
Imaging Method ◽  
Analysis And Design ◽  
Pet Tracer ◽  
Positron Emission

Positron Emission Tomography (PET) produces a three dimensional spatial distribution of positron-electron annihilations within an image volume. Various positron emitters are available for use in aqueous, organic and liquid metal flows. Preliminary experiments at the University of Tennessee at Knoxville (UTK) injected small flows of PET tracer into a bulk water flow in a four rod bundle. The trajectory and diffusion of the tracer in the bulk flow were then mapped using a PET scanner. A spatial resolution of 1.4 mm is achieved with current preclinical Micro-PET imaging equipment resulting in 200 MB 3D activity fields. A time resolved 3-D spatial activity profile was also measured. The PET imaging method is especially well suited to complex geometries where traditional optical methods such as LDV and PIV are difficult to apply. PET methods are uniquely useful for imaging in opaque fluids, opaque pressure boundaries, and multiphase studies. Several commercial and shareware Computational Fluid Dynamics (CFD) codes are currently used for science and engineering analysis and design. These codes produce detailed three dimensional flow predictions. The models produced by these codes are often difficult to validate. The development of this experimental technique offers a modality for the comparison of CFD outcomes with experimental data. Developed data sets from PET can be used in verification and validation exercises of simulation outcomes.

scholarly journals Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Durga M. S. H. Chandrupatla ◽  
Gerrit Jansen ◽  
Elise Mantel ◽  
Philip S. Low ◽  
Takami Matsuyama ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Folate Receptor ◽  
Tracer Uptake ◽  
Response Monitoring ◽  
Distribution Analysis ◽  
Pet Tracer ◽  
Systemic Inflammatory Disease ◽  
Before And After

Background. In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptorβ(FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment.Methods. [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRβexpression.Results. [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p<0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p<0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRβ-positive macrophages were also significantly reduced in liver (5-fold,p<0.005) and spleen (3-fold,p<0.01) of MTX- versus saline-treated rats.Conclusions. MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.

scholarly journals Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis

2021 ◽  
Vol 8 ◽  
Author(s):  
Arghavan Jahandideh ◽  
Mia Ståhle ◽  
Jenni Virta ◽  
Xiang-Guo Li ◽  
Heidi Liljenbäck ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Cell Surface Receptor ◽  
Myocardial Inflammation ◽  
Autoimmune Myocarditis ◽  
Inflammatory Lesions ◽  
Pet Tracer ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

The 68Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([68Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor αvβ3 integrin that is upregulated during angiogenesis and inflammation. We studied whether αvβ3 targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [68Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [68Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUVmean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [68Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing αvβ3 integrin-positive capillary-like structures. A non-specific [68Ga]Ga-DOTA-(RGE)2 tracer showed 76% lower uptake than [68Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that αvβ3 integrin-targeting [68Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.

scholarly journals Synthesis-free PET imaging of brown adipose tissue and TSPO via Combination of Disulfiram and 64CuCl2

2017 ◽  
Author(s):  
Jing Yang ◽  
Jian Yang ◽  
Lu Wang ◽  
Anna Moore ◽  
Steven H. Liang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pet Imaging ◽  
Imaging Biomarker ◽  
Imaging Method ◽  
Steroid Synthesis ◽  
Pet Tracer ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
First Time

AbstractPET imaging is a widely applicable but a very expensive technology. Strategies that can significantly reduce the high cost of PET imaging are highly desirable both for research and commercialization. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18kDa (TSPO) via a combination of Disulfiram, an FDA approved drug for alcoholism, and 64CuCl2 (termed 64Cu-Dis). Our blocking studies, Western blot, and tissue histological imaging suggested that the observed BAT contrast was due to 64Cu-Dis binding to TSPO, which was further confirmed as a specific biomarker for BAT imaging using [18F]-F-DPA, a TSPO-specific PET tracer. Our studies, for the first time, demonstrated that TSPO could serve as a potential imaging biomarker for BAT. Furthermore, since imaging contrast obtained with both 64Cu-Dis and [18F]-F-DPA was not dependent on BAT activation, these agents could be used for reliably imaging BAT mass. Additional value of our synthesis-free approach could be applied to imaging TSPO in other tissues as it is an established biomarker of neuro-inflammation in activated microglia and plays a role in immune response, steroid synthesis, and apoptosis. Although here we applied 64Cu-Dis for a synthesis-free PET imaging of BAT, we believe that our strategy could be extended to other targets while significantly reducing the cost of PET imaging.SignificanceBrown adipose tissue (BAT) has been considered as “good fat,” and large-scale analysis has undoubtedly validated its clinical significance. BAT tightly correlates with body-mass index (BMI), suggesting that BAT bears clear significance for metabolic disorders such as obesity and diabetes. BAT imaging with [18F]-FDG, the most used method for visualizing BAT, primarily reflects BAT activation, but not BAT mass. A convenient imaging method that can consistently reflect BAT mass is still lacking. In this report, we demonstrated that BAT mass can be reliably imaged with a synthesis-free method using the combination of Disulfiram and 64CuCl2 (64Cu-Dis) via TSPO binding. We further demonstrated for the first time that TSPO is a specific imaging biomarker for BAT.

scholarly journals Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Marc Y. Stevens ◽  
Haley C. Cropper ◽  
Katherine L. Lucot ◽  
Aisling M. Chaney ◽  
Kendra J. Lechtenberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Brain Tissue ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Therapeutic Success ◽  
Gamma Counting ◽  
Pet Tracer ◽  
Imaging Results ◽  
Ex Vivo Autoradiography

Abstract Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted. Results Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice. Conclusion CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

scholarly journals Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors

2010 ◽  
Vol 17 (1) ◽  
pp. R53-R73 ◽  
Author(s):  
Dik J Kwekkeboom ◽  
Boen L Kam ◽  
Martijn van Essen ◽  
Jaap J M Teunissen ◽  
Casper H J van Eijck ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pet Imaging ◽  
Tumor Regression ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Receptor Subtype ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Pet Tracer ◽  
First Choice

Somatostatin receptor imaging (SRI) with [111In-DTPA0]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [68Ga-DOTA0,Tyr3]octreotate or [68Ga-DOTA0,Tyr3]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111In-, 90Y-, or 177Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [177Lu-DOTA0,Tyr3]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [177Lu-DOTA0,Tyr3]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.

scholarly journals T166. VISUALIZATION OF AMPA RECEPTORS IN PATIENTS WITH SCHIZOPHRENIA AND DEPRESSION: THE FIRST PET IMAGING STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S294-S295
Author(s):  
Hiroyuki Uchida ◽  
Tomoyuki Miyazaki ◽  
Waki Nakajima ◽  
Mai Hatano ◽  
Hideaki Tani ◽  
...  
Keyword(s):  
Human Brain ◽  
Pet Imaging ◽  
Ampa Receptors ◽  
Molecular Mechanisms ◽  
Nature Medicine ◽  
Standardized Uptake Value ◽  
University Hospital ◽  
Psychiatric Disease ◽  
Whole Brain ◽  
Pet Tracer

Abstract Background Evidence on physiological roles of AMPA receptors in psychiatric conditions, including schizophrenia, has been accumulated, which mainly derives from psychiatric disease model animals as well as post-mortem brain tissues. However, its clinical translation was limited due to lack of any tool to visualize AMPA receptors in living human brain. We have recently developed a new positron emission tomography (PET) probe for AMPA receptors (Miyazaki et al. Nature Medicine, in press). Here, we used the first PET probe that specifically binds to AMPA receptors and successfully visualized these receptors in living human brain of patients with schizophrenia. Methods We developed a novel PET probe for AMPARs, named [11C]K-2 (Miyazaki et al. Nature Medicine, in press). Male patients aged 30–49 with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) underwent a [11C]K-2 PET scan and an MRI scan for co-registration of the PET image and received clinical assessments for symptomatology, including the Positive and Negative Syndrome Scale (PANSS) (registration number: UMIN000025132). [11C]K-2 was synthesized at Yokohama City University Hospital in accordance with GMP ordinance and was certified by the Japanese Society of Nuclear Medicine. PET imaging was performed with a TOSHIBA Aquiduo scanner (TOSHIBA Medical), which provided an axial FOV of 240 mm, and 80 contiguous 2.0 mm thick slices. Standardized uptake value ratio (SUVR)30–50 min with the whole brain and white matter as a reference was calculated, respectively. Results Ten subjects with schizophrenia (mean±SD age, 43.1±3.1 years; duration of illness, 16.8±8.0 years; PANSS total score, 61.7±13.4) participated in this study. There were negative correlations between SUVR30-50 min with the whole brain as a reference in the cingulate gyrus and parahippocampus and PANSS total scores according to the voxel-wise analysis. These correlations were not observed when the while matter was used as a reference. Discussion [11C]K-2 has revealed distinct distribution patterns of AMPA receptors for schizophrenia. Thus, [11C]K-2 is proven to be a potent PET tracer that can be used to visualize AMPARs with high contrast, leading to the elucidation of the molecular mechanisms of schizophrenia.

scholarly journals Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

2021 ◽  
Vol 14 (2) ◽  
pp. 110
Author(s):  
Caitlin Jie ◽  
Valerie Treyer ◽  
Roger Schibli ◽  
Linjing Mu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Second Generation ◽  
Tau Proteins ◽  
Tau Pathology ◽  
Pet Tracer ◽  
Positron Emission ◽  
Tau Pet ◽  
Target Binding

Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

scholarly journals Maximizing the use of batch production of 18F-FDOPA for imaging of brain tumors to increase availability of hybrid PET/MR imaging in clinical setting

2020 ◽  
Author(s):  
M S Aboian ◽  
R Barajas ◽  
J Shatalov ◽  
V Ravanfar ◽  
E Bahroos ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Amino Acid ◽  
Brain Tumors ◽  
Pet Imaging ◽  
Critical Role ◽  
Normal Brain ◽  
Mri Imaging ◽  
Pet Tracer ◽  
Amino Acid Pet ◽  
The Cost

Abstract Background Amino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of post-radiation changes, but is not commonly used in clinical practice due to high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET. Methods Seventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3-5 patients. The first group of consecutively imaged patients contained three patients, followed by two groups of 5 patients, and last group of 4 patients. Results For each of the patients, standard of care gadolinium enhanced MRI and dynamic PET imaging with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28,321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout. Conclusion Amino acid PET tracers have been shown to play a critical role in characterization of brain tumors but their adaptation to clinical practice has been limited due to high cost of PET. Scheduling patient imaging to maximally utilize the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology.

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