scholarly journals Insights into Elution of Anion Exchange Cartridges: Opening the Path towards Aliphatic 18F-Radiolabeling of Base-Sensitive Tracers

2021 ◽  
Author(s):  
Klas Bratteby ◽  
Vladimir Shalgunov ◽  
Umberto Maria Battisti ◽  
Ida Nymann Petersen ◽  
Sara Lopes van den Broek ◽  
...  
Keyword(s):  
Anion Exchange ◽  
Reaction Medium ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Pet Tracers ◽  
High Basicity ◽  
Pet Tracer ◽  
Positron Emission ◽  
Polar Reaction ◽  
Tracer Development

Aliphatic nucleophilic substitution (S<sub>N</sub>2) with [<sup>18</sup>F]fluoride is the most widely applied method to prepare <sup>18</sup>F-labeled positron emission tomography (PET) tracers. Strongly basic conditions commonly used during <sup>18</sup>F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to trap [<sup>18</sup>F]fluoride on anion exchange cartridges and elute it afterwards with basic anions. This sequence is used to facilitate the transfer of [<sup>18</sup>F]fluoride from an aqueous to an aprotic organic, polar reaction medium, which is beneficial for S<sub>N</sub>2 reactions. Furthermore, this sequence also removes cationic radioactive contaminations from cyclotron-irradiated [<sup>18</sup>O]water from which [<sup>18</sup>F]fluoride is produced. In this study, we developed an efficient elution procedure resulting in low basicity that permits S<sub>N</sub>2 <sup>18</sup>F-labeling of base-sensitive scaffolds. Extensive screening of trapping and elution conditions (>1000 experiments) and studying their influence on the radiochemical yield (RCY) allowed us to identify a suitable procedure for this. Four PET tracers and three synthons could be radiolabeled in substantially higher RCYs (up to 2.5-fold), even from lower precursor amounts, using this procedure. Encouraged by these results, we applied our low basicity method to the radiolabeling of highly base-sensitive tetrazines, which cannot be labeled using state-of-art direct aliphatic <sup>18</sup>F-labeling procedures. Labeling succeeded in RCYs of up to 20%. We believe that our findings facilitate PET tracer development by opening the path towards simple and direct S<sub>N</sub>2 <sup>18</sup>F-fluorination of base-sensitive substrates.

scholarly journals Insights into Elution of Anion Exchange Cartridges: Opening the Path towards Aliphatic 18F-Radiolabeling of Base-Sensitive Tracers

2021 ◽  
Author(s):  
Klas Bratteby ◽  
Vladimir Shalgunov ◽  
Umberto Maria Battisti ◽  
Ida Nymann Petersen ◽  
Sara Lopes van den Broek ◽  
...  
Keyword(s):  
Anion Exchange ◽  
Reaction Medium ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Pet Tracers ◽  
High Basicity ◽  
Pet Tracer ◽  
Positron Emission ◽  
Polar Reaction ◽  
Tracer Development

Aliphatic nucleophilic substitution (S<sub>N</sub>2) with [<sup>18</sup>F]fluoride is the most widely applied method to prepare <sup>18</sup>F-labeled positron emission tomography (PET) tracers. Strongly basic conditions commonly used during <sup>18</sup>F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to trap [<sup>18</sup>F]fluoride on anion exchange cartridges and elute it afterwards with basic anions. This sequence is used to facilitate the transfer of [<sup>18</sup>F]fluoride from an aqueous to an aprotic organic, polar reaction medium, which is beneficial for S<sub>N</sub>2 reactions. Furthermore, this sequence also removes cationic radioactive contaminations from cyclotron-irradiated [<sup>18</sup>O]water from which [<sup>18</sup>F]fluoride is produced. In this study, we developed an efficient elution procedure resulting in low basicity that permits S<sub>N</sub>2 <sup>18</sup>F-labeling of base-sensitive scaffolds. Extensive screening of trapping and elution conditions (>1000 experiments) and studying their influence on the radiochemical yield (RCY) allowed us to identify a suitable procedure for this. Four PET tracers and three synthons could be radiolabeled in substantially higher RCYs (up to 2.5-fold), even from lower precursor amounts, using this procedure. Encouraged by these results, we applied our low basicity method to the radiolabeling of highly base-sensitive tetrazines, which cannot be labeled using state-of-art direct aliphatic <sup>18</sup>F-labeling procedures. Labeling succeeded in RCYs of up to 20%. We believe that our findings facilitate PET tracer development by opening the path towards simple and direct S<sub>N</sub>2 <sup>18</sup>F-fluorination of base-sensitive substrates.

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.

scholarly journals Positron Emission Tomography (PET) Imaging of Multiple Myeloma in a Post-Treatment Setting

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 230
Author(s):  
Giulia Ferrarazzo ◽  
Silvia Chiola ◽  
Selene Capitanio ◽  
Maria Isabella Donegani ◽  
Alberto Miceli ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Multiple Myeloma ◽  
Fdg Pet ◽  
Therapy Monitoring ◽  
Emission Tomography ◽  
Clinical Value ◽  
Pet Tracers ◽  
Interpretation Criteria ◽  
Monitoring Therapy ◽  
Positron Emission

2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (FDG PET/CT) has an established clinical value in the diagnosis and initial staging of multiple myeloma (MM). In the last ten years, a vast body of literature has shown that this tool can also be of high relevance for monitoring therapy responses, making it the recommended imaging approach in this field. Starting from the strengths and weaknesses of radiological imaging in MM, the present review aims to analyze FDG PET/CT’s current clinical value focusing on therapy response assessment and objective interpretation criteria for therapy monitoring. Given the potential occurrence of patients with MM showing non-FDG-avid bone disease, new opportunities can be provided by non-FDG PET tracers. Accordingly, the potential role of non-FDG PET tracers in this setting has also been discussed.

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 &lt; 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 &lt; 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 PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 434
Author(s):  
Pierre Cheung ◽  
Bo Zhang ◽  
Emmi Puuvuori ◽  
Sergio Estrada ◽  
Mohammad A. Amin ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Emission Tomography ◽  
Pet Tracer ◽  
Positron Emission ◽  
In Vitro Cell Lines ◽  
Membrane Spanning ◽  
New Strategies

A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [11C]MK-7246 was evaluated in a pig model and in vitro cell lines. The [11C]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [11C]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [11C]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.

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.

Integrated positron emission tomography and magnetic resonance imaging–guided resection of brain tumors: a report of 103 consecutive procedures

2006 ◽  
Vol 104 (2) ◽  
pp. 238-253 ◽  
Author(s):  
Benoît Pirotte ◽  
Serge Goldman ◽  
Olivier Dewitte ◽  
Nicolas Massager ◽  
David Wikler ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Mr Imaging ◽  
Tumor Resection ◽  
Tracer Uptake ◽  
Emission Tomography ◽  
Mr Images ◽  
Pet Tracer ◽  
Positron Emission ◽  
Pet Scanning

Object The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. Methods Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and l-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning–demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection—the tumor contours were displayed in the microscope’s eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. Conclusions Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.

scholarly journals Molecular imaging of metastatic atrial angiosarcoma with positron emission tomography (PET) tracer 3′-deoxy-3′[(18)F]-fluorothymidine, [(18)F]-FLT imaging and early response evaluation

2019 ◽  
Vol 12 (5) ◽  
pp. e218979 ◽  
Author(s):  
Kalevi Kairemo ◽  
Vivek Subbiah
Keyword(s):  
Positron Emission Tomography ◽  
Cell Proliferation ◽  
Proliferation Rate ◽  
Emission Tomography ◽  
Cardiac Tumours ◽  
Flt Pet ◽  
Cardiac Angiosarcoma ◽  
Pet Tracer ◽  
Positron Emission ◽  
Pet Ct

Primary cardiac angiosarcoma, the most common primary cardiac sarcoma has an incidence ranging from 0.001% to 0.028% in autopsy reports with around 200 cases reported in literature. Since a diagnosis of cardiac angiosarcoma portends a poor prognosis, it is vital to ascertain the precise extent of the lesions for follow-up. Imaging with positron emission tomography (PET) tracer 2-deoxy-2-[18F]-fluoro-D-glucose in cardiac angiosarcoma is challenging as myocardium takes up glucose and delineation of tumour becomes difficult. Cell proliferation rate in normal cardiac muscular tissue is low whereas cardiac tumours display a higher proliferation rate. This aspect could be exploited by use of 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (18F-FLT PET/CT] in cardiac tumours where the cell proliferation could be measured. Herein, we imaged an index case of cardiac angiosarcoma using18F-FLT PET/CT and report the findings.

scholarly journals Preparation of a First 18F-Labeled Agonist for M1 Muscarinic Acetylcholine Receptors

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2880 ◽  
Author(s):  
Boris D. Zlatopolskiy ◽  
Felix Neumaier ◽  
Till Rüngeler ◽  
Birte Drewes ◽  
Niklas Kolks ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Radiochemical Yield ◽  
Muscarinic Acetylcholine Receptors ◽  
Preparative Scale ◽  
Muscarinic Acetylcholine ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Applications ◽  
M1 Muscarinic ◽  
Subtype Selective

M1 muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer’s disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several 11C-labeled probes. However, protocols for the preparation of 18F-labeled mAChR-ligands have not been published so far. Here, we describe a straightforward procedure for the preparation of an 18F-labeled M1 mAChR agonist and its corresponding pinacol boronate radiolabeling precursor and the non-radioactive reference compound. The target compounds were prepared from commercially available aryl fluorides and Boc protected 4-aminopiperidine using a convergent reaction protocol. The radiolabeling precursor was prepared by a modification of the Miyaura reaction and labeled via the alcohol-enhanced Cu-mediated radiofluorination. The developed procedure afforded the radiotracer in a non-decay-corrected radiochemical yield of 17 ± 3% (n = 3) and in excellent radiochemical purity (>99%) on a preparative scale. Taken together, we developed a straightforward protocol for the preparation of an 18F-labeled M1 mAChR agonist that is amenable for automation and thus provides an important step towards the routine production of a 18F-labeled M1 selective PET tracer for experimental and diagnostic applications.

Sign in / Sign up

Export Citation Format

Share Document