scholarly journals Current Perspectives on 89Zr-PET Imaging

2020 ◽  
Vol 21 (12) ◽  
pp. 4309
Author(s):  
Joon-Kee Yoon ◽  
Bok-Nam Park ◽  
Eun-Kyoung Ryu ◽  
Young-Sil An ◽  
Su-Jin Lee
Keyword(s):  
Pet Imaging ◽  
Cell Tracking ◽  
Current Status ◽  
Cancer Therapies ◽  
Ongoing Research ◽  
Positron Emission ◽  
Nanoparticle Imaging ◽  
Anti Cancer ◽  
Preclinical And Clinical Studies

89Zr is an emerging radionuclide that plays an essential role in immuno-positron emission tomography (PET) imaging. The long half-life of 89Zr (t1/2 = 3.3 days) is favorable for evaluating the in vivo distribution of monoclonal antibodies. Thus, the use of 89Zr is promising for monitoring antibody-based cancer therapies. Immuno-PET combines the sensitivity of PET with the specificity of antibodies. A number of studies have been conducted to investigate the feasibility of 89Zr immuno-PET imaging for predicting the efficacy of radioimmunotherapy and antibody therapies, imaging target expression, detecting target-expressing tumors, and the monitoring of anti-cancer chemotherapies. In this review, we summarize the current status of PET imaging using 89Zr in both preclinical and clinical studies by highlighting the use of immuno-PET for the targets of high clinical relevance. We also present 89Zr-PET applications other than immuno-PET, such as nanoparticle imaging and cell tracking. Finally, we discuss the limitations and the ongoing research being performed to overcome the remaining hurdles.

scholarly journals Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides)

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 704
Author(s):  
Alessandra Cavaliere ◽  
Katrin C. Probst ◽  
Stephen J. Paisey ◽  
Christopher Marshall ◽  
Abdul K. H. Dheere ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Pet Imaging ◽  
Early Stage ◽  
Proof Of Concept ◽  
Synthesis Time ◽  
Positron Emission ◽  
Anti Cancer ◽  
Radiochemical Yields ◽  
Radiochemical Synthesis

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3′- and 2′-fluorinated ProTides following different radiosynthetic approaches. The 3′-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15–30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2′-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1–5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min).

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar
Keyword(s):  
Cancer Treatment ◽  
Atmospheric Plasma ◽  
Current Status ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Long Time ◽  
Key Topics ◽  
The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals 11C- and 18F-Radiotracers for In Vivo Imaging of the Dopamine System: Past, Present and Future

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 108
Author(s):  
Michael R. Kilbourn
Keyword(s):  
Pet Imaging ◽  
In Vivo Imaging ◽  
Dopamine Synthesis ◽  
Dopamine System ◽  
Synaptic Release ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Pet Radiotracers ◽  
Selection Of

The applications of positron emission tomography (PET) imaging to study brain biochemistry, and in particular the aspects of dopamine neurotransmission, have grown significantly over the 40 years since the first successful in vivo imaging studies in humans. In vivo PET imaging of dopaminergic functions of the central nervous system (CNS) including dopamine synthesis, vesicular storage, synaptic release and receptor binding, and reuptake processes, are now routinely used for studies in neurology, psychiatry, drug abuse and addiction, and drug development. Underlying these advances in PET imaging has been the development of the unique radiotracers labeled with positron-emitting radionuclides such as carbon-11 and fluorine-18. This review focuses on a selection of the more accepted and utilized PET radiotracers currently available, with a look at their past, present and future.

scholarly journals Non-invasive imaging of the coronary arteries

2018 ◽  
Vol 40 (29) ◽  
pp. 2444-2454 ◽  
Author(s):  
Philip D Adamson ◽  
David E Newby
Keyword(s):  
Coronary Arteries ◽  
Randomized Clinical Trials ◽  
Rapid Development ◽  
Current Status ◽  
Future Research ◽  
Research Perspective ◽  
Non Invasive ◽  
Positron Emission ◽  
Prognostic Stratification

Abstract Non-invasive imaging of the coronary arteries is an enterprise in rapid development. From the research perspective, there is great demand for in vivo techniques that can reliably identify features of high-risk plaque that may offer insight into pathophysiological processes and act as surrogate indicators of response to therapeutic intervention. Meanwhile, there is clear clinical need for greater accuracy in diagnosis and prognostic stratification. Fortunately, ongoing technological improvements and emerging data from randomized clinical trials are helping make these elusive goals a reality. This review provides an update on the current status of non-invasive coronary imaging with computed tomography, magnetic resonance, and positron emission tomography with a focus on current clinical applications and future research directions.

scholarly journals Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuming Zhao ◽  
Dengyang Zhang ◽  
Yao Guo ◽  
Bo Lu ◽  
Zhizhuang Joe Zhao ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Malignant Tumors ◽  
Wnt Signaling Pathway ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Functional Features ◽  
Survival Signaling ◽  
Preclinical And Clinical Studies ◽  
Canonical Wnt

Receptor tyrosine kinase ROR1 plays an essential role in embryogenesis and is overexpressed in many types of malignant tumors. Studies have demonstrated that it plays an important role in oncogenesis by activating cell survival signaling events, particularly the non-canonical WNT signaling pathway. Antibody-based immunotherapies targeting ROR1 have been developed and evaluated in preclinical and clinical studies with promising outcomes. However, small molecule inhibitors targeting ROR1 are underappreciated because of the initial characterization of ROR1 as a peusdokinase. The function of ROR1 as a tyrosine kinase remains poorly understood, although accumulating evidence have demonstrated its intrinsic tyrosine kinase activity. In this review, we analyzed the structural and functional features of ROR1 and discussed therapeutic strategies targeting this kinase.

STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging

2021 ◽  
Vol 118 (36) ◽  
pp. e2105390118 ◽  
Author(s):  
Keke Liang ◽  
Evan R. Abt ◽  
Thuc M. Le ◽  
Arthur Cho ◽  
Amanda M. Dann ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Cell Metabolism ◽  
Nucleotide Metabolism ◽  
Type I Interferons ◽  
Ductal Adenocarcinoma ◽  
Type I ◽  
Flt Pet ◽  
Positron Emission ◽  
Pharmacodynamic Biomarkers

Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these agents is the lack of noninvasive pharmacodynamic biomarkers that indicate increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity, but whether IFN signaling–induced alterations in tumor cell metabolism can be detected using PET has not been investigated. We found that IFN signaling augments pancreatic ductal adenocarcinoma (PDAC) cell nucleotide metabolism via transcriptional induction of metabolism-associated genes including thymidine phosphorylase (TYMP). TYMP catalyzes the first step in the catabolism of thymidine, which competitively inhibits intratumoral accumulation of the nucleoside analog PET probe 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). Accordingly, IFN treatment up-regulates cancer cell [18F]FLT uptake in the presence of thymidine, and this effect is dependent upon TYMP expression. In vivo, genetic activation of stimulator of interferon genes (STING), a PRR highly expressed in PDAC, enhances the [18F]FLT avidity of xenograft tumors. Additionally, small molecule STING agonists trigger IFN signaling–dependent TYMP expression in PDAC cells and increase tumor [18F]FLT uptake in vivo following systemic treatment. These findings indicate that [18F]FLT accumulation in tumors is sensitive to IFN signaling and that [18F]FLT PET may serve as a pharmacodynamic biomarker for STING agonist–based therapies in PDAC and possibly other malignancies characterized by elevated STING expression.

scholarly journals [18F]AZD2461, an Insight on Difference in PARP Binding Profiles for DNA Damage Response PET Imaging

2020 ◽  
Vol 22 (5) ◽  
pp. 1226-1234
Author(s):  
Florian Guibbal ◽  
Samantha L. Hopkins ◽  
Anna Pacelli ◽  
Patrick G. Isenegger ◽  
Michael Mosley ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Cell Uptake ◽  
Pancreatic Cell ◽  
Anti Cancer ◽  
Damage Response ◽  
Automated Procedures

Abstract Background Poly (ADP-ribose) polymerase (PARP) inhibitors are extensively studied and used as anti-cancer drugs, as single agents or in combination with other therapies. Most radiotracers developed to date have been chosen on the basis of strong PARP1–3 affinity. Herein, we propose to study AZD2461, a PARP inhibitor with lower affinity towards PARP3, and to investigate its potential for PARP targeting in vivo. Methods Using the Cu-mediated 18F-fluorodeboronation of a carefully designed radiolabelling precursor, we accessed the 18F-labelled isotopologue of the PARP inhibitor AZD2461. Cell uptake of [18F]AZD2461 in vitro was assessed in a range of pancreatic cell lines (PSN-1, PANC-1, CFPAC-1 and AsPC-1) to assess PARP expression and in vivo in xenograft-bearing mice. Blocking experiments were performed with both olaparib and AZD2461. Results [18F]AZD2461 was efficiently radiolabelled via both manual and automated procedures (9 % ± 3 % and 3 % ± 1 % activity yields non-decay corrected). [18F]AZD2461 was taken up in vivo in PARP1-expressing tumours, and the highest uptake was observed for PSN-1 cells (7.34 ± 1.16 %ID/g). In vitro blocking experiments showed a lesser ability of olaparib to reduce [18F]AZD2461 binding, indicating a difference in selectivity between olaparib and AZD2461. Conclusion Taken together, we show the importance of screening the PARP selectivity profile of radiolabelled PARP inhibitors for use as PET imaging agents.

scholarly journals Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64 Cu-Macrin in Mice, Rabbits, and Pigs

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Matthias Nahrendorf ◽  
Friedrich Felix Hoyer ◽  
Anu E. Meerwaldt ◽  
Mandy M.T. van Leent ◽  
Max L. Senders ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Flow Cytometry ◽  
Confocal Microscopy ◽  
Pet Imaging ◽  
Near Infrared ◽  
Emission Tomography ◽  
Imaging Biomarker ◽  
Positron Emission ◽  
Pulmonary Macrophages

Background: Macrophages, innate immune cells that reside in all organs, defend the host against infection and injury. In the heart and vasculature, inflammatory macrophages also enhance tissue damage and propel cardiovascular diseases. Methods: We here use in vivo positron emission tomography (PET) imaging, flow cytometry, and confocal microscopy to evaluate quantitative noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer 64 Cu-Macrin—a 20-nm spherical dextran nanoparticle assembled from nontoxic polyglucose. Results: PET imaging using 64 Cu-Macrin faithfully reported accumulation of macrophages in the heart and lung of mice with myocardial infarction, sepsis, or pneumonia. Flow cytometry and confocal microscopy detected the near-infrared fluorescent version of the nanoparticle ( VT680 Macrin) primarily in tissue macrophages. In 5-day-old mice, 64 Cu-Macrin PET imaging quantified physiologically more numerous cardiac macrophages. Upon intravenous administration of 64 Cu-Macrin in rabbits and pigs, we detected heightened macrophage numbers in the infarcted myocardium, inflamed lung regions, and atherosclerotic plaques using a clinical PET/magnetic resonance imaging scanner. Toxicity studies in rats and human dosimetry estimates suggest that 64 Cu-Macrin is safe for use in humans. Conclusions: Taken together, these results indicate 64 Cu-Macrin could serve as a facile PET nanotracer to survey spatiotemporal macrophage dynamics during various physiological and pathological conditions. 64 Cu-Macrin PET imaging could stage inflammatory cardiovascular disease activity, assist disease management, and serve as an imaging biomarker for emerging macrophage-targeted therapeutics.

Sign in / Sign up

Export Citation Format

Share Document