PET Imaging of Adenosine Receptors in Diseases

2019 ◽  
Vol 19 (16) ◽  
pp. 1445-1463 ◽  
Author(s):  
Jindian Li ◽  
Xingfang Hong ◽  
Guoquan Li ◽  
Peter S. Conti ◽  
Xianzhong Zhang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Adenosine Receptors ◽  
Neurological Diseases ◽  
G Protein Coupled Receptors ◽  
Extracellular Adenosine ◽  
Positron Emission ◽  
Imaging Probes ◽  
Pet Probes ◽  
Cancer And Inflammation ◽  
G Protein Coupled

Adenosine receptors (ARs) are a class of purinergic G-protein-coupled receptors (GPCRs). Extracellular adenosine is a pivotal regulation molecule that adjusts physiological function through the interaction with four ARs: A1R, A2AR, A2BR, and A3R. Alterations of ARs function and expression have been studied in neurological diseases (epilepsy, Alzheimer’s disease, and Parkinson’s disease), cardiovascular diseases, cancer, and inflammation and autoimmune diseases. A series of Positron Emission Tomography (PET) probes for imaging ARs have been developed. The PET imaging probes have provided valuable information for diagnosis and therapy of diseases related to alterations of ARs expression. This review presents a concise overview of various ARs-targeted radioligands for PET imaging in diseases. The most recent advances in PET imaging studies by using ARs-targeted probes are briefly summarized.

scholarly journals In VivoPET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Anna Vuorimaa ◽  
Eero Rissanen ◽  
Laura Airas
Keyword(s):  
Immune System ◽  
Pet Imaging ◽  
Neurological Diseases ◽  
Suppressive Effect ◽  
Receptor Targeting ◽  
Additional Tool ◽  
Positron Emission ◽  
The Central Nervous System ◽  
G Protein Coupled

Adenosine receptors are G-protein coupled P1 purinergic receptors that are broadly expressed in the peripheral immune system, vasculature, and the central nervous system (CNS). Within the immune system, adenosine 2A (A2A) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS,A2Areceptors are expressed mainly within the neurons of the basal ganglia. Alterations inA2Areceptor function and expression have been noted in movement disorders, and in Parkinson’s disease pharmacologicalA2Areceptor antagonism leads to diminished motor symptoms. AlthoughA2Areceptors are expressed only at a low level in the healthy CNS outside striatum, pathological challenge or inflammation has been shown to lead to upregulation ofA2Areceptors in extrastriatal CNS tissue, and this has been successfully quantitated usingin vivopositron emission tomography (PET) imaging andA2Areceptor-binding radioligands. Several radioligands for PET imaging ofA2Areceptors have been developed in recent years, andA2Areceptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammationin vivo. This review article provides a brief overview ofA2Areceptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances inA2Areceptor-targeting PET imaging studies.

scholarly journals Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 925
Author(s):  
Margit Pissarek
Keyword(s):  
G Protein ◽  
Cannabinoid Receptors ◽  
G Protein Coupled Receptors ◽  
Translocator Protein ◽  
Brain Diseases ◽  
Present Contribution ◽  
Binding Behavior ◽  
Positron Emission ◽  
Inflammatory Processes ◽  
G Protein Coupled

Inflammatory processes preceding clinical manifestation of brain diseases are moving increasingly into the focus of positron emission tomographic (PET) investigations. A key role in inflammation and as a target of PET imaging efforts is attributed to microglia. Cerebellar microglia, with a predominant ameboid and activated subtype, is of special interest also regarding improved and changing knowledge on functional involvement of the cerebellum in mental activities in addition to its regulatory role in motor function. The present contribution considers small molecule ligands as potential PET tools for the visualization of several receptors recognized to be overexpressed in microglia and which can potentially serve as indicators of inflammatory processes in the cerebellum. The sphingosine 1 phosphate receptor 1 (S1P1), neuropeptide Y receptor 2 (NPY2) and purinoceptor Y12 (P2Y12) cannabinoid receptors and the chemokine receptor CX3CR1 as G-protein-coupled receptors and the ionotropic purinoceptor P2X7 provide structures with rather classical binding behavior, while the immune receptor for advanced glycation end products (RAGE) and the triggering receptor expressed on myeloid cells 2 (TREM2) might depend for instance on further accessory proteins. Improvement in differentiation between microglial functional subtypes in comparison to the presently used 18 kDa translocator protein ligands as well as of the knowledge on the role of polymorphisms are special challenges in such developments.

scholarly journals A2B Adenosine Receptor and Cancer

2019 ◽  
Vol 20 (20) ◽  
pp. 5139 ◽  
Author(s):  
Zhan-Guo Gao ◽  
Kenneth A. Jacobson
Keyword(s):  
G Proteins ◽  
Anticancer Agents ◽  
Immune Suppression ◽  
Adenosine Receptors ◽  
Immune Surveillance ◽  
G Protein Coupled Receptors ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
G Protein Coupled

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors (GPCRs). Locally produced adenosine is a suppressant in anti-tumor immune surveillance. The A2BAR, coupled to both Gαs and Gαi G proteins, is one of the several GPCRs that are expressed in a significantly higher level in certain cancer tissues, in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are novel, potentially attractive anticancer agents. Several antagonists targeting A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various cancers, and the rationale of using A2BAR antagonists in cancer therapy.

scholarly journals [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

2016 ◽  
Vol 113 (15) ◽  
pp. 4027-4032 ◽  
Author(s):  
Woosuk Kim ◽  
Thuc M. Le ◽  
Liu Wei ◽  
Soumya Poddar ◽  
Jimmy Bazzy ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Cytidine Deaminase ◽  
Cross Reactivity ◽  
Leukemia Cells ◽  
Deoxycytidine Kinase ◽  
Specificity And Sensitivity ◽  
Positron Emission ◽  
Pet Ct ◽  
Deoxyguanosine Kinase ◽  
Pet Probes

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds—[18F]Clofarabine; 2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-adenine ([18F]CFA) and 2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-guanine ([18F]F-AraG)—for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [18F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [18F]F-AraG is a better substrate for dGK than for dCK. [18F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [18F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [18F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [18F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [18F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

Role and Function of Adenosine and its Receptors in Inflammation, Neuroinflammation, IBS, Autoimmune Inflammatory Disorders, Rheumatoid Arthritis and Psoriasis

2019 ◽  
Vol 25 (26) ◽  
pp. 2875-2891 ◽  
Author(s):  
Ashok K. Shakya ◽  
Rajashri R. Naik ◽  
Ihab M. ALMASRI ◽  
Avneet Kaur
Keyword(s):  
Rheumatoid Arthritis ◽  
Adenosine Receptors ◽  
G Protein Coupled Receptors ◽  
Physiological Effects ◽  
Xanthine Derivatives ◽  
Organ Systems ◽  
New Chemical Entities ◽  
And Function ◽  
G Protein Coupled ◽  
Role And Function

The physiological effects of endogenous adenosine on various organ systems are very complex and numerous which are elicited upon activation of any of the four G-protein-coupled receptors (GPCRs) denoted as A1, A2A, A2B and A3 adenosine receptors (ARs). Several fused heterocyclic and non-xanthine derivatives are reported as a possible target for these receptors due to physiological problems and lack of selectivity of xanthine derivatives. In the present review, we have discussed the development of various new chemical entities as a target for these receptors. In addition, compounds acting on adenosine receptors can be utilized in treating diseases like inflammation, neuroinflammation, autoimmune and related diseases.

scholarly journals Extracellular adenosine: a critical signal in liver fibrosis

2018 ◽  
Vol 315 (1) ◽  
pp. G12-G19 ◽  
Author(s):  
Michel Fausther
Keyword(s):  
Liver Fibrosis ◽  
G Protein Coupled Receptors ◽  
Critical Signal ◽  
Extracellular Adenosine ◽  
Matrix Deposition ◽  
Liver Myofibroblasts ◽  
Health And Disease ◽  
Research Questions ◽  
Current Lines ◽  
G Protein Coupled

Extracellular adenosine nucleoside is a potent, endogenous mediator that signals through specific G protein-coupled receptors, and exerts pleiotropic effects on liver physiology, in health and disease. Particularly, adenosinergic or adenosine-mediated signaling pathways impact the progression of hepatic fibrosis, a common feature of chronic liver diseases, through regulation of matrix deposition by liver myofibroblasts. This review examines the current lines of evidence on adenosinergic regulation of liver fibrosis and myofibroblasts, identifies unanswered research questions, and proposes important future areas of investigation.

scholarly journals A2B Adenosine Receptor and Cancer

2019 ◽  
Author(s):  
Zhan-Guo Gao ◽  
Kenneth A. Jacobson
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Anticancer Agents ◽  
Immune Suppression ◽  
Adenosine Receptors ◽  
G Protein Coupled Receptors ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
G Protein Coupled

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors. The A2BAR, coupled to both Gαi and Gαq G proteins, is one of the several G-protein-coupled receptors that are expressed in a significantly higher level in some cancer tissues in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are potentially novel attractive anticancer agents. Several antagonists targeting at the A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various types cancers, and the rationale of using A2BAR antagonists in cancer therapy

A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers

Cephalalgia ◽  
2013 ◽  
Vol 33 (10) ◽  
pp. 853-860 ◽  
Author(s):  
Katarina Varnäs ◽  
Aurelija Jučaitė ◽  
Dennis J McCarthy ◽  
Per Stenkrona ◽  
Magdalena Nord ◽  
...  
Keyword(s):  
Human Subjects ◽  
Negative Relationship ◽  
Receptor Occupancy ◽  
G Protein Coupled Receptors ◽  
Binding Potential ◽  
Healthy Male ◽  
Orodispersible Tablets ◽  
Positron Emission ◽  
Significant Negative Relationship ◽  
G Protein Coupled

Aim To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administration of the antimigraine drug zolmitriptan. Methods Positron emission tomography (PET) studies were undertaken using the radioligand [11C]AZ10419369 in eight control subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examined after two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart. Two of the subjects were subsequently examined after administration of 5 mg zolmitriptan. One week after the last administration of zolmitriptan five of the subjects underwent additional PET measurements without drug pretreatment. Results After administration of 10 mg zolmitriptan, mean receptor occupancy was 4–5%. No consistent changes in 5-HT1B receptor binding were observed for subjects who received 5 mg zolmitriptan. There was a statistically significant negative relationship between binding potential ( BPND) and plasma concentration of zolmitriptan and the active metabolite 183C91, respectively. All of the five subjects who were examined 1 week after dosing with zolmitriptan showed higher BPND post drug administration compared with baseline. Conclusion This is the first demonstration of CNS 5-HT1B receptor occupancy of a triptan. The findings are consistent with the low receptor occupancy previously reported in PET studies with agonists at other G protein coupled receptors.

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