Synthesis and evaluation of 6-arylaminobenzamides as positron emission tomography imaging ligands for the sphingosine-1-phosphate-5 receptor.

The sphingosine-1-phosphate-5 (S1P) receptor is one of the five membrane G protein-coupled receptors that are activated by the lysophospholipid, sphingosine-1-phosphate, resulting in regulation of many cellular processes. S1P receptors are located on oligodendrocytes and are proposed to influence oligodendrocyte physiology. Understanding S1P modulation during processes such as remyelination could have potential applications for demyelinating CNS disorders such as multiple sclerosis (MS).

Ligand-Enabled Copper-Mediated Radioiodination of Arenes.

The discovery of a copper precatalyst that facilitates the key mechanistic steps of arene halodeboronation has allowed a step change in the synthesis of radioiodine-containing arenes. The active precatalyst [Cu(OAc)(phen)]OAc was shown to perform room temperature radio-iododeboronation of aryl boronic acids with 1-2 mol % loadings and 10 min reaction times. These mild conditions enable particularly clean reactions, as demonstrated with the efficient preparation of the radiopharmaceutical and SPECT tracer, -iodobenzylguanidine (MIBG).

Sexually dimorphic murine brain uptake of the 18 kDa translocator protein PET radiotracer [F]LW223.

The 18 kDa translocator protein is a well-known biomarker of neuroinflammation, but also plays a role in homeostasis. PET with 18 kDa translocator protein radiotracers [C]PBR28 in humans and [F]GE180 in mice has demonstrated sex-dependent uptake patterns in the healthy brain, suggesting sex-dependent 18 kDa translocator protein expression, although humans and mice had differing results. This study aimed to assess whether the 18 kDa translocator protein PET radiotracer [F]LW223 exhibited sexually dimorphic uptake in healthy murine brain and peripheral organs.

The Effects of Human Papillomavirus Status and Treatment on the Positive Predictive Value of Post-radiotherapy F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Advanced Head and Neck Squamous Cell Carcinoma.

Aims: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status.

[F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging.

Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [F]LW223, in mice and specifically assess its volume of non-displaceable binding () in brain as well as investigate the use of simplified analysis approaches for quantification of [F]LW223 PET data.

A Comparative Evaluation of Mediastinal Nodal SUVmax and Derived Ratios from F-FDG PET/CT Imaging to Predict Nodal Metastases in Non-Small Cell Lung Cancer.

F-FDG positron emission tomography with computed tomography (PET/CT) is a standard imaging modality for the nodal staging of non-small cell lung cancer (NSCLC). To improve the accuracy of pre-operative staging, we compare the staging accuracy of mediastinal lymph node (LN) standard uptake values (SUV) with four derived SUV ratios based on the SUV values of primary tumours (TR), the mediastinal blood pool (MR), liver (LR), and nodal size (SR). In 2015-2017, 53 patients (29 women and 24 men, mean age 67.

Long term survival in patients with human papillomavirus-positive oropharyngeal cancer and equivocal response on 12-week PET-CT is not compromised by the omission of neck dissection.

Background And Aim: The aim of this study was to evaluate the long-term safety of the omission of immediate neck dissections (IND) in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) achieving a less than complete nodal response on 12-week FDG PET-CT.

Material And Methods: Patients with HPV-positive, node-positive HNSCC that were treated with radical (chemo) radiotherapy (RT) between January 2013 and September 2019 were identified. PET-CT responses were classified as complete (CR), incomplete (ICR) or equivocal (EQR) nodal responses.

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling.

Background: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach.

Objectives: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules.

Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules.

Introduction: Dynamic contrast-enhanced CT (DCE-CT) and positron emission tomography/CT (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules (SPNs). The aim of this study was to compare the accuracy and cost-effectiveness of these.

Methods: In this prospective multicentre trial, 380 participants with an SPN (8-30 mm) and no recent history of malignancy underwent DCE-CT and PET/CT.

Modelling [F]LW223 PET data using simplified imaging protocols for quantification of TSPO expression in the rat heart and brain.

Purpose: To provide a comprehensive assessment of the novel 18 kDa translocator protein (TSPO) radiotracer, [F]LW223, kinetics in the heart and brain when using a simplified imaging approach.

Methods: Naive adult rats and rats with surgically induced permanent coronary artery ligation received a bolus intravenous injection of [F]LW223 followed by 120 min PET scanning with arterial blood sampling throughout. Kinetic modelling of PET data was applied to estimated rate constants, total volume of distribution (V) and binding potential transfer corrected (BP) using arterial or image-derived input function (IDIF).

The relationship between F-FDG-PETCT-derived tumour metabolic activity, nutritional risk, body composition, systemic inflammation and survival in patients with lung cancer.

The aim of this study was to examine the relationship between PET-CT derived tumour glucose uptake as measured by maximum standard glucose uptake (SUVmax) and total lesion glycolysis (TLG), nutritional risk as measured by the malnutrition universal screening tool (MUST), CT derived body composition as measured by skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), the systemic inflammatory response as measured by the modified Glasgow prognostic score (mGPS) and the neutrophil to lymphocyte ratio (NLR) and survival in patients with lung cancer, treated with radiotherapy. In a retrospective cohort study, 119 patients were included in final analyses. The majority of patients were over 65 (86%), female (52%), had a performance status (ECOG-PS) of 0 or 1 (57%), were at nutritional risk (57%), were overweight (53%), had visceral obesity (62%), had a normal SMI (51%), had a low SMD (62%) and were systemically inflammed (mGPS 1/2, 51%).

18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy.

Background: Prostate cancer is highly prevalent worldwide. Androgen deprivation therapy (ADT) remains the treatment of choice for incurable prostate cancer, but majority of patients develop disease recurrence following ADT. There is therefore an urgent need for early detection of treatment resistance.

Positron Emission Tomography-Computed Tomography Surveillance after (Chemo)Radiotherapy in Advanced Head and Neck Squamous Cell Cancer: Beyond the PET-NECK Protocol.

Aims: To evaluate the implementation of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) surveillance after (chemo)radiotherapy, to compare outcomes for those who achieved a complete (CR), equivocal (EQR) and incomplete (ICR) nodal response on 12-week PET-CT according to their human papillomavirus (HPV) status, and to assess the safety of ongoing surveillance beyond 12 weeks in the HPV-positive EQR group.

Materials And Methods: All patients with node-positive head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy between January 2013 and September 2017 were identified. PET-CT responses were classified as CR, ICR or EQR.

Deoxyfluorination with CuF : Enabled by Using a Lewis Base Activating Group.

Deoxyfluorination is a primary method for the formation of C-F bonds. Bespoke reagents are commonly used because of issues associated with the low reactivity of metal fluorides. Reported here is the development of a simple strategy for deoxyfluorination, using first-row transition-metal fluorides, and it overcomes these limitations.

Effect of F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial.

Purpose: Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of F-fluciclovine on management of men with BCR of prostate cancer.

Methods And Materials: Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites.

12 week PET-CT has low positive predictive value for nodal residual disease in human papillomavirus-positive oropharyngeal cancers.

Objectives: Surveillance PET-CT scans at 12 weeks post-radiotherapy for head and neck cancer can be used to omit neck dissections with no detriment in overall survival. Human Papillomavirus (HPV) driven tumours behave differently on conventional imaging after radiotherapy but it is unknown if this effect is seen on PET-CT and if HPV status affects the accuracy of PET-CT. We aimed to determine the negative and positive predictive values (NPV and PPV) of 12 week surveillance PET-CT in HPV positive and negative tumours, and investigate predictors of relapse in equivocal responders.

Kinetic modelling and quantification bias in small animal PET studies with [18F]AB5186, a novel 18 kDa translocator protein radiotracer.

Introduction: Positron Emission Tomography (PET) imaging with selective 18 kDa translocator protein (TSPO) radiotracers has contributed to our understanding on the role of inflammation in disease development and progression. With an increasing number of rodent models of human disease and expansion of the preclinical PET imaging base worldwide, accurate quantification of longitudinal rodent TSPO PET datasets is necessary. This is particularly relevant as TSPO PET quantification relies on invasive blood sampling due to lack of a suitable tissue reference region.

Mechanism of Cu-Catalyzed Aryl Boronic Acid Halodeboronation Using Electrophilic Halogen: Development of a Base-Catalyzed Iododeboronation for Radiolabeling Applications.

An investigation into the mechanism of Cu-catalyzed aryl boronic acid halodeboronation using electrophilic halogen reagents is reported. Evidence is provided to show that this takes place via a boronate-driven ipso-substitution pathway and that Cu is not required for these processes to operate: general Lewis base catalysis is operational. This in turn allows the rational development of a general, simple, and effective base-catalyzed halodeboronation that is amenable to the preparation of I-labeled products for SPECT applications.

The Relationship Between Tumor Glucose Metabolism and Host Systemic Inflammatory Responses in Patients with Cancer: A Systematic Review.

One of the most important and long recognized characteristics of tumor cells is their dysregulated cellular energetics with anaerobic driven glucose uptake. In patients with cancer, the prognostic value of the systemic inflammatory response has been well established, and the recent combination of PET and CT scanning combines the assessment of tumor physiologic activity with detailed anatomic localization. The aim of this study was to perform a systematic review of the assessment of the relationship between both the tumor and the host inflammatory responses using PET/CT.

An F-Labeled Poly(ADP-ribose) Polymerase Positron Emission Tomography Imaging Agent.

Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1).

Rapid Iododeboronation with and without Gold Catalysis: Application to Radiolabelling of Arenes.

Radiopharmaceuticals that incorporate radioactive iodine in combination with single-photon emission computed tomography imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for the incorporation of radioiodine into small molecules. This work reports a rapid air- and moisture-stable ipso-iododeboronation procedure that uses NIS in the non-toxic, green solvent dimethyl carbonate.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

Introduction: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently.

Silver(I)-Catalyzed Iodination of Arenes: Tuning the Lewis Acidity of N-Iodosuccinimide Activation.

A mild and rapid method for the iodination of arenes that utilizes silver(I) triflimide as a catalyst for activation of N-iodosuccinimide has been developed. The transformation was found to be general for a wide range of anisole, aniline, acetanilide, and phenol derivatives and allowed the late-stage iodination of biologically active compounds such as PIMBA, a SPECT imaging agent of breast cancer, and (-)-IBZM, a dopamine D2 receptor antagonist. The method was also modified for the radioiodination of arenes using a one-pot procedure involving the in situ generation of [(125)I]-N-iodosuccinimide followed by the silver(I)-catalyzed iodination.