Potential PET Research Articles

Antimicrobial peptide LyeTx I mn∆K labeled with 68Ga is a potential PET radiopharmaceutical for molecular imaging of infections

BackgroundAntimicrobial peptides have been radiolabeled and investigated as molecular diagnostic probes due to their propensity to accumulate in infectious sites rather than aseptic inflammatory lesions. LyeTx I is a cationic peptide from the venom of Lycosa erythrognatha, exhibiting significant antimicrobial activity. LyeTx I mn∆K is a shortened derivative of LyeTx I, with an optimized balance between antimicrobial and hemolytic activities. This study reports the first 68Ga-radiolabeling of the DOTA-modified LyeTx I mn∆K and primarily preclinical evaluations of [68Ga]Ga-DOTA(K)-LyeTx I mn∆K as a PET radiopharmaceutical for infection imaging. MethodsDOTA(K)-LyeTx I mn∆K was radiolabeled with freshly eluted 68Ga. Radiochemical yield (RCY), radiochemical purity (RCP), and radiochemical stability (in saline and serum) were evaluated using ascending thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (RP-HPLC). The radiopeptide's lipophilicity was assessed by determining the logarithm of the partition coefficient (Log P). Serum protein binding (SBP) and binding to Staphylococcus aureus (S. aureus) cells were determined in vitro. Ex vivo biodistribution studies and PET/CT imaging were conducted in healthy mice (control) and mice with infection and aseptic inflammation to evaluate the potential of [68Ga]Ga-DOTA(K)-LyeTx I mn∆K as a specific PET radiopharmaceutical for infections. Results[68Ga]Ga-DOTA(K)-LyeTx I mn∆K was obtained with a high RCY (>90 %), and after purification through a Sep-Pak C18 cartridge, the RCP exceeded 99 %. Ascending TLC and RP-HPLC showed that the radiopeptide remained stable for up to 3.0 h in saline solution and up to 1.5 h in murine serum. [68Ga]Ga-DOTA(K)-LyeTx I mn∆K exhibited hydrophilic characteristics (Log P = −2.4 ± 0.1) and low SPB (ranging from 23.3 ± 0.4 % at 5 min of incubation to 10.5 ± 1.1 % at 60 min of incubation). The binding of [68Ga]Ga-DOTA(K)-LyeTx I mn∆K to S. aureus cells was proportional to bacterial concentration, with binding percentages of 8.8 ± 0.5 % (0.5 × 109 CFU.mL−1), 16.2 ± 1.4 % (1.0 × 109 CFU.mL−1), and 62.2 ± 0.6 % (5.0 × 109 CFU.mL−1). Ex vivo biodistribution studies and PET/CT images showed higher radiopeptide uptake at the infection site compared to the aseptic inflammation site; the latter was similar to the control group. Target-to-non-target (T/NT) ratios obtained by ex vivo biodistribution data were approximately 1.0, 1.3, and 3.0 at all investigated time intervals for the control, aseptic inflammation, and infection groups, respectively. Furthermore, T/NT ratios obtained from PET/CT images were 1.1 ± 0.1 for the control group and 1.4 ± 0.1 for the aseptic inflammation group. For the infection group, T/NT ratio was 5.0 ± 0.3, approximately 5 times greater compared to the former groups. ConclusionsThe results suggest the potential of [68Ga]Ga-DOTA(K)-LyeTx I mn∆K as a PET radiopharmaceutical for molecular imaging of infections.

First-in-human study of D6-[18F]FP-(+)-DTBZ, a novel VMAT2 tracer: whole-body biodistribution and brain PET comparison with [18F]FP-(+)-DTBZ (AV-133)

BackgroundIn the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients.ResultsThe automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline).ConclusionsD6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain.Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725.

Recyclable Enzymatic Hydrolysis with Metal–Organic Framework Stabilized Humicola insolens Cutinase (HiC) for Potential PET Upcycling

Recyclable Enzymatic Hydrolysis with Metal–Organic Framework Stabilized Humicola insolens Cutinase (HiC) for Potential PET Upcycling

Exploring Thermal Discomfort during Mediterranean Heatwaves through Softscape and Hardscape ENVI-Met Simulation Scenarios

The study examines the effectiveness of various design strategies in alleviating the impacts of heatwaves in the Mediterranean region, focusing on a densely populated post-refugee urban area in Greece. By analyzing five different design scenarios, the study aims to identify the most efficient approach to mitigate thermal stress outdoors. The five design scenarios include changes in albedo values and coatings and alterations in the number and type of trees. The methodology includes a literature review, field work and microclimate simulations with the use of ENVI-met 5.6.1. The study evaluates ENVI-met data through potential air temperature, PET and UTCI analysis. The experimental results indicate that the most effective strategy is associated with urban greening. In particular, increasing tree cover considerably reduces air temperature, PET and UTCI values by 4 to 10 degrees Celsius. This finding highlights the potential of urban greening to enhance thermal comfort and combat heatwave effects. The research findings may be useful to landscape architects and urban designers, in light of a more climate-responsive urban design in the Mediterranean region. Future research may also assess the combined impact of multiple mitigation strategies on a larger scale, informing evidence-based policies for heatwave resilience.

Unveiling potential PET degrading eukaryotes through in silico bioprospecting of PETases

This study addresses the environmental problem of PET plastic through in silico bioprospecting for the identification and experimental validation of novel PET degrading eukaryotes through the in silico bioprospectingI of PETases, employing a methodology that combines Hidden Markov Models (HMMs), clustering techniques, molecular docking, and dynamic simulations. A total of 424 putative PETase sequences were identified from 219 eukaryotic organisms, highlighting six sequences with low affinity energies. The Aspergillus luchuensis sequence showed the lowest Gibbs free energy and exhibited stability at different temperatures in molecular dynamics assays. Experimental validation, through a plate clearance assay and HPLC, confirmed PETase activity in three wild-type fungal strains, with A. luchuensis showing the highest efficiency. The results obtained demonstrate the effectiveness of combining computational and experimental approaches as proof of concept to discover and validate eukaryotes with PET-degrading capabilities opening new perspectives for the sustainable management of this type of waste and contributing to its environmental mitigation.

Synthesis and Preclinical Evaluation of Novel 68Ga-DOTA-RBB as Potential PET Radiotracer for Imaging CDK4/6 in Tumors.

Many malignant tumors, including breast cancer, exhibit amplification and overexpression of cyclin-dependent kinase 4 and 6 (CDK4/6). Ribociclib, approved and used in clinical treatment, acts as a highly selective CDK4/6 inhibitor for ER+/HER2- breast cancer. By modifying ribociclib with the chelator DOTA, we designed and synthesized a novel CDK4/6-positive PET imaging agent, which was radiolabeled by 68Ga for radioactive tagging. The radiotracer demonstrates high radiochemical purity, excellent stability in vitro and in vivo, and favorable pharmacokinetic characteristics. Cell uptake experiments using MCF-7 cells indicate that an excess of ribociclib (RBB) can inhibit cellular uptake of 68Ga-DOTA-RBB. Imaging and biodistribution experiments in MCF-7 tumor-bearing nude mice show significant radioactive accumulation in the tumor. However, preadministration of excess ribociclib results in a substantial reduction in radioactive accumulation within the tumor. On the basis of our explorations, 68Ga-DOTA-RBB, as a targeted imaging agent for CDK4/6-positive tumors, holds significant potential application values.

Synthesis of 18F‐labeled Aryl Trifluoromethyl Sulfones, ‐Sulfoxides, and ‐Sulfides for Positron Emission Tomography

AbstractPositron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3‐groups. For instance, S(O)nCF3‐groups (n=0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n=1, 2). Herein, we describe general methods for the radiosynthesis of 18F‐labeled aryl trifluoromethyl sulfones, ‐sulfoxides, and ‐sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert‐Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F‐labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers.

Radiation dosimetry of para-chloro-2-[18F]fluoroethyl-etomidate: a PET tracer for adrenocortical imaging

Background[11C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer’s rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[18F]fluoroethyl-etomidate, [18F]CETO, a fluorine-18 (T1/2=109.8 min) analogue, as a potential new adrenocortical PET tracer. The aim of this study was to assess radiation dosimetry of [18F]CETO.Results[18F]CETO showed a high uptake in adrenal glands, still increasing at 5 h post injection. Adrenal glands (absorbed dose coefficients 0.100 ± 0.032 mGy/MBq in males and 0.124 ± 0.013 mGy/MBq in females) received the highest absorbed dose. The effective dose coefficient was 20 µSv/MBq.Conclusions[18F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET examination with 200 MBq [18F]CETO is 4 mSv.Trial registrationClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, URL: https://clinicaltrials.gov/ct2/show/NCT05361083.

Intramolecular Friedel-Crafts Acylation of [11C]Isocyanates Enabling the Radiolabeling of [carbonyl-11C]DPQ.

α,β-aromatic lactams are highly abundant in biologically active molecules, yet so far they cannot be radiolabeled with short-lived (t1/2=20.3 min), β+-decaying carbon-11, which has prevented their application as positron emission tomography tracers. Herein, we developed, optimized, and applied a widely applicable, one-pot, quick, robust and automatable radiolabeling method for α,β-aromatic lactams starting from [11C]CO2 using the reagent POCl3⋅AlCl3. This method proceeds via intramolecular Friedel-Crafts acylation of in situ formed [11C]isocyanates and shows a broad substrate scope for the formation of five- and six-membered rings. We implemented our developed labeling method for the radiosynthesis of the potential PARP1 PET tracer [carbonyl-11C]DPQ in a clinical radiotracer production facility following the standards of the European Pharmacopoeia.

Paw some Connection: Pet Adoption and Donation

"Paw some Connection" is a comprehensive project aimed at promoting pet adoption and facilitating donations for animal welfare organizations. The initiative seeks to address the growing issue of abandoned and stray animals by creating a user-friendly platform that connects potential pet parents with rescue animals in need of loving homes. This project integrates an intuitive adoption portal, where users can browse profiles of pets available for adoption, learn about their stories, and connect with shelters or foster families. Additionally, a streamlined donation system is incorporated to support the financial needs of these organizations, ensuring proper care, medical attention, and rehabilitation for rescued animals. The platform leverages modern technology and social media integration to amplify its reach, encouraging a wider audience to engage in the noble cause of providing safe and caring environments for animals. By fostering a sense of community and compassion, "Paw some Connection" aims to make a positive impact on the lives of both pets and humans, creating lasting connections that benefit all involved parties. Keywords: Comprehensive project, Promoting pet adoption, Facilitating donations, User-friendly platform.

Arginine-Selective Bioconjugation Reagent for Effective 18F-labeling of Native Proteins.

Protein-based 18F-PET tracers offer new possibilities in early disease detection and personalized medicine. Their development relies heavily on the availability and effectiveness of 18F-prosthetic groups. We prepared and evaluated a novel arginine-selective prosthetic group, 4-[18F]fluorophenylglyoxal ([18F]FPG). [18F]FPG was radiosynthesized by a one-pot, two-step procedure with a non-decay-corrected (n.d.c.) isolated radiochemical yield (RCY) of 41 ± 8% (n = 10). [18F]FPG constitutes a generic tool for 18F-labeling of various proteins, including human serum albumin (HSA), ubiquitin, interleukin-2, and interleukin-4 in ∼30-60% n.d.c. isolated RCYs. [18F]FPG conjugation with arginine residues is highly selective, even in the presence of a large excess of lysine, cysteine, and histidine. [18F]FPG protein conjugates are able to preserve the binding affinity of the native proteins while also demonstrating excellent in vivo stability. The [18F]FPG-HSA conjugate has prolonged blood retention, which can be applied as a potential blood pool PET imaging agent. Thus, [18F]FPG is an arginine-selective bioconjugation reagent that can be effectively used for the development of 18F-labeled protein radiopharmaceuticals.

EYE TRACKER AS A TOOL SUPPORTING DIFFERENTIAL DIAGNOSIS IN THE STATES OF DISORDES OF CONSCIOUSNESS (DOC)

One of the key parameters in the evaluation of disorders of consciousness (DOC) is visual behavior. In the past, visual potential testing or PET scanning was mainly used to assess these parameters. Recently, Eye Tracker (ET) technology for assessing visual functions has emerged; however, there are only a few publications devoted to the use of this technology in assessing people with disorders of consciousness (DOC). The purpose of this study was to evaluate the feasibility of using ET in the diagnosis of visual functioning in DOC patients.The study group consisted 25 patients (8 women and 17 men) awakened from prolonged post-traumatic coma in the Care and Treatment Facility of the "Light" Foundation in Toruń. The coma occurred as a result of severe brain damage: brain injury, stroke or sudden cardiac arrest. The mean age was 39.83 (SD 11.88) for the entire group, 38.85 (SD 9.99) for women, and 40.23 (SD 12.84) for men. All of these patients were in various states of disorders of consciousness (DOC), which was examined using the Coma Recovery Scale-Revised (CRS-R) (Giaciano et al., 2004). Appropriate inclusion and exclusion criteria were applied based on examinations by an internal medical physician and an ophthalmologist. Important exclusion criteria from the study were infection, elevated temperature, visual impairment and patient agitation. The visual functioning of the patients was measured with the use of the Eye Tracker Tobii X-120 device.A significant difference in visual functioning was demonstrated primarily in the areas of (1) reaction time to first fixation, where the Minimal Consciousness State minus (MCS-) group showed a significantly longer reaction time compared to the Minimal Consciousness State plus (MCS+) and the Emergency of Minimal Consciousness State (EMCS) groups; (2) fixation duration, where the MCS- group showed a longer time compared to patients in the MCS+ and EMCS groups; (3) the number of fixation points on the screen, where the MCS- group showed a significantly lower number of fixation points compared to the MCS+ and EMCS groups.Eye Tracker Tobii X-120 can serve as a valuable tool to aid in the neuropsychological diagnosis of individuals experiencing states of reduced consciousness. Indicators that most differentiate between the different levels of impaired consciousness include the time to the first fixation, the number of fixation points on the screen and the total number of fixations.

P-113 - Design and synthesis of fluorinated pyrazolidine-3,5-dione derivatives as potential P2Y12 receptor PET tracers

P-113 - Design and synthesis of fluorinated pyrazolidine-3,5-dione derivatives as potential P2Y12 receptor PET tracers

P-210 - Synthesis of a carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET tracer for imaging of PI3K/mTOR in cancer

P-210 - Synthesis of a carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET tracer for imaging of PI3K/mTOR in cancer

P-096 - Novel pyrazolethiazole derivatives as a promising new class of ligands for alpha-synuclein fibrils and potential PET tracers for the detection of α-synucleinopathies

P-096 - Novel pyrazolethiazole derivatives as a promising new class of ligands for alpha-synuclein fibrils and potential PET tracers for the detection of α-synucleinopathies

Evaluation of 2-deoxy-2-[18F]fluoro glucaric acid (FGA) as a potential PET tracer for tumor necrosis

In this study, [18F]FGA was obtained by a one-step oxidation of [18F]FDG using sodium hypochlorite. The conversion from [18F]FDG to [18F]FGA was confirmed by HPLC to be over 95% using the optimal condition. A549-luciferase NSCLC xenografted mice was used for in vivo PET imaging. Prior to either saline or cisplatin treatment, there was no significant difference on tumor uptake of [18F]FGA in all mice, with an average uptake of (0.21 ± 0.16) %ID/g. After treatment, tumor uptake of [18F]FGA was not changed significantly for saline-treated mice, whereas the tumor uptake of [18F]FGA drastically increased for cisplatin-treated mice, with an average uptake of (1.63 ± 0.16) %ID/g. The ratio of tumor uptake between cisplatin-treated vs. saline-treated mice was 7.8 ± 0.2 within one week of treatment. PET imaging results were consistent with ex vivo biodistribution data. BLI showed significant light intensity suppression after treatment, indicating necrosis. Our data indicate that [18F]FGA uptake was related to tumor necrosis. [18F]FGA PET/CT imaging might be a useful tool to monitor treatment response to chemotherapy by imaging tumor necrosis.

Composting-based degradation of poly (ethylene terephthalate) microplastics and its enhancement with exogenous PET hydrolase supplementation

Poly (ethylene terephthalate) (PET) constitutes an important composition of environmental microplastics (MPs). This study was to explore the degradation of PET MPs in high-temperature composting and also to make an attempt for an enhanced degradation by exogenous addition of thermophilic PET hydrolase. Herein, six 220 L composters were applied to perform the composting, with half designated enhanced group with PET hydrolase added. After 20 days, PET MPs exhibited a notable reduction (21.1%) in weight and the addition of PET hydrolase resulted in 32.8% reduction of PET MPs. This is also corroborated by the increase of terephthalic acid (one of PET degradation products) from 2.0μg/g sample in initial mixture to 3.7μg/g sample in composting group and 9.3μg/g sample in enhanced group. Besides, the particle size distribution of PET MPs shifted toward smaller sizes after composting, with the supplementation of PET hydrolase further accentuating this shift. After composting, the surface of PET MPs in both treatments exhibited conspicuous corrosion and oxidation. An analysis of publicly available compost metagenomes indicated the wide distribution of potential PET hydrolase and TPA 1,2-dioxygenase genes. These findings suggest that composting exhibited a noticeable performance in the degradation of PET MPs and enzyme-assisted composting enhanced the degradation, providing a new approach for addressing environmental microplastics pollution.

Integrin αvβ3 and EGFR dual-targeted [64Cu]Cu-NOTA-RGD-GE11 heterodimer for PET imaging in pancreatic cancer mouse model

PurposeRadiolabeled heterodimeric peptide has emerged as a highly promising targeting strategy for PET imaging due to their superior properties. RGD and GE11 are two peptides binding to receptor integrin αvβ3 and EGFR, respectively, which both overexpress in many different types of tumors. This study focuses on the synthesis and evaluation of a RGD and GE11-containing heterodimeric radiotracer [64Cu]Cu-NOTA-RGD-GE11 for PET imaging of tumors that simultaneously overexpress integrin αvβ3 and EGFR. Procedures[64Cu]Cu-NOTA-RGD-GE11 was prepared by the conjugation of RGD-PEG4-NOTA-N3 and GE11-PEG4-BCN via metal-free click chemistry, followed by radiolabeling with 64Cu. Cell uptake and efflux studies, saturation binding assay, the animal PET/CT and biodistribution studies were conducted to characterize the biological properties of [64Cu]Cu-NOTA-RGD-GE11. Results[64Cu]Cu-NOTA-RGD-GE11 was synthesized with a radiochemical purity of >97 % and molar activity of 23 GBq/μmol at the end of synthesis. [64Cu]Cu-NOTA-RGD-GE11 showed moderate hydrophilicity, good stability in mouse serum and high specific uptake by the human pancreatic cancer cell line (BxPC3) in the in vitro studies. Compared to the two monomeric counterparts [64Cu]Cu-NOTA-RGD and [64Cu]Cu-NOTA-GE11, [64Cu]Cu-NOTA-RGD-GE11 demonstrated significantly improved tumor uptakes (e.g. 4.63 ± 0.25 %ID/g vs 1.24 ± 0.18 %ID/g and 0.77 ± 0.13 %ID/g, 2 h after injection, p < 0.05) in the subsequent in vivo evaluation in mice bearing BxPC3 xenograft. Tumor uptake could be blocked in the presence of both non-radioactive c(RGDyK) and GE11 peptides, indicating good tumor specificity of [64Cu]Cu-NOTA-RGD-GE11 in vivo. ConclusionThe results suggested that the as-developed [64Cu]Cu-NOTA-RGD-GE11 could serve as a potential PET tracer for the noninvasive imaging of integrin αvβ3 and EGFR expression in tumors.

Deep learning model for automatic image quality assessment in PET

BackgroundA variety of external factors might seriously degrade PET image quality and lead to inconsistent results. The aim of this study is to explore a potential PET image quality assessment (QA) method with deep learning (DL).MethodsA total of 89 PET images were acquired from Peking Union Medical College Hospital (PUMCH) in China in this study. Ground-truth quality for images was assessed by two senior radiologists and classified into five grades (grade 1, grade 2, grade 3, grade 4, and grade 5). Grade 5 is the best image quality. After preprocessing, the Dense Convolutional Network (DenseNet) was trained to automatically recognize optimal- and poor-quality PET images. Accuracy (ACC), sensitivity, specificity, receiver operating characteristic curve (ROC), and area under the ROC Curve (AUC) were used to evaluate the diagnostic properties of all models. All indicators of models were assessed using fivefold cross-validation. An image quality QA tool was developed based on our deep learning model. A PET QA report can be automatically obtained after inputting PET images.ResultsFour tasks were generated. Task2 showed worst performance in AUC,ACC, specificity and sensitivity among 4 tasks, and task1 showed unstable performance between training and testing and task3 showed low specificity in both training and testing. Task 4 showed the best diagnostic properties and discriminative performance between poor image quality (grade 1, grade 2) and good quality (grade 3, grade 4, grade 5) images. The automated quality assessment of task 4 showed ACC = 0.77, specificity = 0.71, and sensitivity = 0.83, in the train set; ACC = 0.85, specificity = 0.79, and sensitivity = 0.91, in the test set, respectively. The ROC measuring performance of task 4 had an AUC of 0.86 in the train set and 0.91 in the test set. The image QA tool could output basic information of images, scan and reconstruction parameters, typical instances of PET images, and deep learning score.ConclusionsThis study highlights the feasibility of the assessment of image quality in PET images using a deep learning model, which may assist with accelerating clinical research by reliably assessing image quality.

2‐Nitroimidazole Based PET Tracers: Development of a General Synthetic Approach and Fluorination Methodology

Abstract2‐Nitroimidazole based PET tracers are widely used for non‐invasive hypoxic tumor diagnosis. In this context, we report here a general method based on a central Mitsunobu reaction to easily access 2‐nitroimidazole precursors. Optimization of fluorination conditions is described and successfully applied to the radiofluorination of the 2‐nitroimidazole precursors. Moreover, the radiosynthesis of a new potential hypoxia PET tracer is also described. Finally, this article presents a SFC analytical method allowing both an easy monitoring of the fluorination reactions and the measurement of partition coefficients (logP).