Synthesis and Binding Affinity of a Fluorine-Substituted Peroxisome Proliferator-Activated Gamma (PPARγ) Ligand as a Potential Positron Emission Tomography (PET) Imaging Agent

2007 ◽  
Vol 18 (2) ◽  
pp. 507-513 ◽  
Author(s):  
Byung Chul Lee ◽  
Kyo Chul Lee ◽  
Hsiaoju Lee ◽  
Robert H. Mach ◽  
John A. Katzenellenbogen
Keyword(s):  
Positron Emission Tomography ◽  
Binding Affinity ◽  
Pet Imaging ◽  
Emission Tomography ◽  
Imaging Agent ◽  
Peroxisome Proliferator ◽  
Positron Emission

scholarly journals Direct Aromatic 18F-Labeling of Highly Reactive Tetrazines for Pretargeted Bioorthogonal PET Imaging

2021 ◽  
Author(s):  
Rocio Garcia-Vazquez ◽  
Umberto Maria Battisti ◽  
Jesper Tranekjær Jørgensen ◽  
Vladimir Shalgunov ◽  
Lars Hvass ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Clinical Translation ◽  
Emission Tomography ◽  
Imaging Agent ◽  
Conventional Imaging ◽  
Bioorthogonal Reaction ◽  
Positron Emission ◽  
Tetrazine Ligation

Pretargeted bioorthogonal imaging can be used to visualize and quantify slow accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct18 F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct 18 F-labeling procedure has been developed and applied to obtain a pretargeting tetrazine-based imaging agent with favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

scholarly journals Direct Aromatic 18F-Labeling of Highly Reactive Tetrazines for Pretargeted Bioorthogonal PET Imaging

2021 ◽  
Author(s):  
Rocio Garcia-Vazquez ◽  
Umberto Maria Battisti ◽  
Jesper Tranekjær Jørgensen ◽  
Vladimir Shalgunov ◽  
Lars Hvass ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Clinical Translation ◽  
Emission Tomography ◽  
Imaging Agent ◽  
Conventional Imaging ◽  
Bioorthogonal Reaction ◽  
Positron Emission ◽  
Tetrazine Ligation

Pretargeted bioorthogonal imaging can be used to visualize and quantify slow accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct18 F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct 18 F-labeling procedure has been developed and applied to obtain a pretargeting tetrazine-based imaging agent with favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

scholarly journals Identification, Characterization, and Optimization of Integrin αvβ6-Targeting Peptides from a One-Bead One-Compound (OBOC) Library: Towards the Development of Positron Emission Tomography (PET) Imaging Agents

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 309 ◽  
Author(s):  
Yng Tang ◽  
Ryan Davis ◽  
Tanushree Ganguly ◽  
Julie Sutcliffe
Keyword(s):  
Positron Emission Tomography ◽  
Binding Affinity ◽  
Pet Imaging ◽  
Emission Tomography ◽  
Imaging Agents ◽  
Screening Assay ◽  
Positron Emission ◽  
Integrin Αvβ6 ◽  
Peptide Imaging ◽  
The One

The current translation of peptides identified through the one-bead one-compound (OBOC) technology into positron emission tomography (PET) imaging agents is a slow process, with a major delay between ligand identification and subsequent lead optimization. This work aims to streamline the development process of 18F-peptide based PET imaging agents to target the integrin αvβ6. By directly identify αvβ6–targeting peptides from a 9-mer 4-fluorobenzoyl peptide library using the on-bead two-color (OBTC) cell-screening assay, a total of 185 peptide beads were identified and 5 beads sequenced for further evaluation. The lead peptide 1 (VGDLTYLKK(FB), IC50 = 0.45 ± 0.06 μM, 25% stable in serum at 1 h) was further modified at the N-, C-, and bi-termini. C-terminal PEGylation increased the metabolic stability (>95% stable), but decreased binding affinity (IC50 = 3.7 ± 1 μM) was noted. C-terminal extension (1i, VGDLTYLKK(FB)KVART) significantly increased binding affinity for integrin αvβ6 (IC50 = 0.021 ± 0.002 μM), binding selectivity for αvβ6-expressing cells (3.1 ± 0.8:1), and the serum stability (>99% stable). Our results demonstrate the challenges in optimizing OBOC-derived peptides, indicate both termini of 1 are sensitive to modifications, and show that further modification of 1 is necessary to demonstrate utility as an 18F-peptide imaging agent.

Usefulness of positron emission tomography for differentiating gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system

2020 ◽  
Vol 133 (4) ◽  
pp. 1010-1019 ◽  
Author(s):  
Hiroaki Takei ◽  
Jun Shinoda ◽  
Soko Ikuta ◽  
Takashi Maruyama ◽  
Yoshihiro Muragaki ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Who Classification ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
World Health ◽  
Pet Tracers ◽  
Positron Emission ◽  
Significant Difference ◽  
The Mean

OBJECTIVEPositron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification.METHODSIn total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers.RESULTSThere were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG.CONCLUSIONSPET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.

Role of Positron Emission Tomography for Central Nervous System Involvement in Systemic Autoimmune Diseases: Status and Perspectives

2018 ◽  
Vol 25 (26) ◽  
pp. 3096-3104 ◽  
Author(s):  
Daniele Mauro ◽  
Gaetano Barbagallo ◽  
Salvatore D`Angelo ◽  
Pasqualina Sannino ◽  
Saverio Naty ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Diseases ◽  
Pet Imaging ◽  
Emission Tomography ◽  
Cns Involvement ◽  
Systemic Autoimmune Diseases ◽  
Positron Emission

In the last years, an increasing interest in molecular imaging has been raised by the extending potential of positron emission tomography [PET]. The role of PET imaging, originally confined to the oncology setting, is continuously extending thanks to the development of novel radiopharmaceutical and to the implementation of hybrid imaging techniques, where PET scans are combined with computed tomography [CT] or magnetic resonance imaging[MRI] in order to improve spatial resolution. Early preclinical studies suggested that 18F–FDG PET can detect neuroinflammation; new developing radiopharmaceuticals targeting more specifically inflammation-related molecules are moving in this direction. Neurological involvement is a distinct feature of various systemic autoimmune diseases, i.e. Systemic Lupus Erythematosus [SLE] or Behcet’s disease [BD]. Although MRI is largely considered the gold-standard imaging technique for the detection of Central Nervous System [CNS] involvement in these disorders. Several patients complain of neuropsychiatric symptoms [headache, epilepsy, anxiety or depression] in the absence of any significant MRI finding; in such patients the diagnosis relies mainly on clinical examination and often the role of the disease process versus iatrogenic or reactive forms is doubtful. The aim of this review is to explore the state-of-the-art for the role of PET imaging in CNS involvement in systemic rheumatic diseases. In addition, we explore the potential role of emerging radiopharmaceutical and their possible application in aiding the diagnosis of CNS involvement in systemic autoimmune diseases.

Direct incorporation of [ 18F] into aliphatic systems: A promising Mncatalysed labelling technique for PET imaging

2020 ◽  
Vol 13 ◽  
Author(s):  
Sara Cesarec ◽  
Jonathan A. Robson ◽  
Laurence S. Carroll ◽  
Eric O. Aboagye ◽  
Alan C. Spivey
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Emission Tomography ◽  
Labelling Technique ◽  
Porphyrin Complex ◽  
Mild Conditions ◽  
Drug Substances ◽  
Positron Emission ◽  
Site Selective ◽  
Direct Incorporation

Background: One of the challenges in positron emission tomography (PET) is labelling complex aliphatic molecules. Objective: To develop a method of metal-catalysed radiofluorination that is site-selective and works in moderate to good yields under facile conditions. Methods: We report here on the optimisation of an aliphatic C-H to C-18F bond transformation catalysed by a Mn(porphyrin) complex. Results: The successful oxidation of 11 aliphatic molecules including progesterone are reported. Radiochemical Incorporations (RCIs) up to 69% were achieved within 60 min without the need for pre-activation or specialist equipment. Conclusion: The method features mild conditions (60 °C) and promises to constitute a valuable approach to labelling of biomolecules and drug substances.

Sign in / Sign up

Export Citation Format

Share Document