Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand.

Background: Heart-type fatty acid binding proteins (FABP3) constitute a family of lipid chaperone proteins. They are found in the cytosol and enhance cellular fatty acid solubilisation, transport, and metabolism. FABP3 is highly expressed in the myocardium and is released from myocytes during myocardial damage.

Process validation and preclinical development of a new PET cerebral blood flow tracer [C]MMP for initial clinical trials.

Background: 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) is commonly used for diagnosis of dementia because brain glucose metabolism reflects neuronal activity. However, as [F]FDG is an analogue of glucose, accumulation of tracer in the brain is affected by plasma glucose levels. In contrast, cerebral blood flow (CBF) tracers are theoretically unaffected by plasma glucose levels and are therefore expected to be useful alternatives for the diagnosis of dementia in patients with diabetes.

Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [F]FSW-100 for clinical applications.

Background: Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [F]FSW-100 radiosynthesis, including the F-fluorination reaction, semipurification of the F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand.

Phantom and clinical evaluation of the Bayesian penalised likelihood reconstruction algorithm Q.Clear without PSF correction in amyloid PET images.

Purpose: Bayesian penalised likelihood (BPL) reconstruction, which incorporates point-spread-function (PSF) correction, provides higher signal-to-noise ratios and more accurate quantitation than conventional ordered subset expectation maximization (OSEM) reconstruction. However, applying PSF correction to brain PET imaging is controversial due to Gibbs artefacts that manifest as unpredicted cortical uptake enhancement. The present study aimed to validate whether BPL without PSF would be useful for amyloid PET imaging.

Preclinical validation of a novel brain-penetrant PET ligand for visualization of histone deacetylase 6: a potential imaging target for neurodegenerative diseases.

Purpose: Histone deacetylase 6 (HDAC6) has emerged as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease. Noninvasive imaging of HDAC6 in the brain by positron emission tomography (PET) would accelerate research into its roles in these diseases. We recently discovered an F-labeled derivative of the selective HDAC6 inhibitor SW-100 ([F]FSW-100) as a potential candidate for brain HDAC6 radioligand.

Pitfalls of Amyloid-Beta PET: Comparisons With 18 F-MK-6240 and 18 F-THK5351 PET.

We present 3 patients as pitfalls of amyloid-beta (Aβ) PET, who underwent 11 C-PiB (Aβ), 18 F-MK-6240 (Alzheimer disease [AD]-tau), and 18 F-THK5351 (astrogliosis) PET examinations. Despite negligible or tiny Aβ pathology, patients 1 and 2 were diagnosed with AD as the cause of symptoms. Despite widespread Aβ pathology, patient 3 was not diagnosed with AD as the cause of symptoms.

A gold-complex initiated functionalization of biologically active polyphenols applied to a F-labeled chemical probe.

(-)-Epigallocatechin gallate (EGCG), a key component of green tea, exerts therapeutic anticancer and antiallergic properties through its binding to the 67 kDa laminin receptor. The functionalization of EGCG is a promising strategy for creating new drug candidates and chemical probes. In our study, we developed a method for effectively modifying the A ring of EGCG through an electrophilic aromatic substitution with amidomethyl 2-alkynylbenzoates initiated with a gold complex.

Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice.

The nucleotide second messenger 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP) mediate fundamental functions of the brain, including learning and memory. Phosphodiesterase 3 (PDE3) can hydrolyze both cAMP and cGMP and appears to be involved in the regulation of their contents in cells. We previously demonstrated that long-term administration of cilostazol, a PDE3 inhibitor, maintained good memory performance in aging mice.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Main Body: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry.

Distribution Pattern of the Monoamine Oxidase B Ligand, 18F-THK5351, in the Healthy Brain.

Background: 18F-THK5351 PET estimates the concentrations of monoamine oxidase B (MAO-B) that are preferentially located in astrocytes and can be used to visualize and quantify ongoing astrogliosis. To study images of astrogliosis in neurological disorders, it is essential to understand the detailed binding sites of 18F-THK5351 as the MAO-B ligand under normal conditions. In this study, we examined the detailed distribution pattern of 18F-THK5351 in the healthy brain by comparing 18F-THK5351 uptake between subjects taking and not taking the MAO-B inhibitor.

Possibility of Enlargement in Left Medial Temporal Areas Against Cerebral Amyloid Deposition Observed During Preclinical Stage.

Neurodegenerative changes in the preclinical stage of Alzheimer's disease (AD) have recently been the focus of attention because they may present a range of treatment opportunities. A total of 134 elderly volunteers who lived in a local community were investigated and grouped into preclinical and mild cognitive impairment stages according to the Clinical Dementia Rating test; we also estimated amyloid deposition in the brain using positron emission tomography (PET). A significant interaction between clinical stage and amyloid PET positivity on cerebral atrophy was observed in the bilateral parietal lobe, parahippocampal gyri, hippocampus, fusiform gyrus, and right superior and middle temporal gyri, as previously reported.

Determination of optimal regularization factor in Bayesian penalized likelihood reconstruction of brain PET images using [ F]FDG and [ C]PiB.

Purpose: The Bayesian penalized likelihood (BPL) reconstruction algorithm, Q.Clear, can achieve a higher signal-to-noise ratio on images and more accurate quantitation than ordered subset-expectation maximization (OSEM). The reconstruction parameter (β) in BPL requires optimization according to the radiopharmaceutical tracer.

Adenosine A Receptor Occupancy by Caffeine After Coffee Intake in Parkinson's Disease.

Background: Coffee intake can decrease the risk for Parkinson's disease (PD). Its beneficial effects are allegedly mediated by caffeine through adenosine A receptor (A R) antagonist action.

Objective: We aimed to calculate occupancy rates of striatal A Rs by caffeine after coffee intake in PD.

Radiosynthesis and in Vivo and ex Vivo Evaluation of Isomeric [C]methoxy Analogs of Nimesulide as Brain Cyclooxygenase-2-Targeted Imaging Agents.

Our previous studies identified that nimesulide analogs which bear a methoxy substituent at the para-position of the phenyl ring could be potential radiotracer candidates for detecting disorders related to cyclooxygenase-2 (COX-2) expression and activity in vivo using positron emission tomography (PET) in the brain. The present study was conducted to evaluate the in vivo characteristics of C-labeled para-methoxy nimesulide ([C]1d) as a brain COX-2-targeted imaging agent compared to other isomeric methoxy analogs of nimesulide ([C]1b and [C]1c). [C]1b-d were synthesized with reasonable yield and purity by the methylation of the O-desmethyl precursor with [C]methyl triflate in the presence of NaOH at room temperature.

Test-retest reproducibility of cerebral adenosine A receptor quantification using [C]preladenant.

Objective: To evaluate the reproducibility of cerebral adenosine A receptor (AR) quantification using [C]preladenant ([C]PLN) and PET in a test-retest study.

Methods: Eight healthy male volunteers were enrolled. Dynamic 90 min PET scans were performed twice at the same time of the day to avoid the effect of diurnal variation.

First clinical assessment of [F]MC225, a novel fluorine-18 labelled PET tracer for measuring functional P-glycoprotein at the blood-brain barrier.

Objective: 5-(1-(2-[F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen ([F]MC225) is a selective substrate for P-glycoprotein (P-gp), possessing suitable properties for measuring overexpression of P-gp in the brain. This is the first-in-human study to examine safety, radiation dosimetry and P-gp function at the blood-brain barrier (BBB) of [F]MC225 in healthy subjects.

Methods: [F]MC225 biodistribution and dosimetry were determined in 3 healthy male subjects, using serial 2 h and intermittent 4 and 6 h whole-body PET scans acquired after [F]MC225 injection.

Correlation of 4'-[methyl-11C]-thiothymidine PET with Ki-67 immunohistochemistry separately in patients with newly diagnosed and recurrent gliomas.

Objective: 4'-[methyl-11C]-thiothymidine (4DST) uptake on PET was correlated with proliferative activity separately in patients with newly diagnosed and recurrent gliomas.

Methods: A total of 29 patients, 18 with newly diagnosed gliomas and 11 with recurrent gliomas who underwent 4DST PET/computed tomography (CT) were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) of tumor (T) and the mean SUV of normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined.

Texture indices of 4'-[methyl-C]-thiothymidine uptake predict p16 status in patients with newly diagnosed oropharyngeal squamous cell carcinoma: comparison with F-FDG uptake.

Background: In oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus (HPV)/p16 status is important as a prognostic biomarker.

Purpose: We evaluated the relationship between 4'-[methyl-C]-thiothymidine (C-4DST) and F-FDG PET texture indices and p16 status in patients with newly diagnosed OPSCC.

Methods: We retrospectively reviewed the collected data of 256 consecutive, previously untreated patients with primary head and neck tumors enrolled between November 2011 and October 2019.

Head-to-head comparison of (R)-[C]verapamil and [F]MC225 in non-human primates, tracers for measuring P-glycoprotein function.

Purpose: P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. (R)-[C]verapamil is considered the gold standard tracer to measure the P-gp function; however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [F]MC225.

Correlation of 4'-[methyl-C]-thiothymidine PET with Gd-enhanced and FLAIR MRI in patients with newly diagnosed glioma.

Purpose: To elucidate the biological association between tumor proliferation, tumor infiltration and neovascularization, we analyzed the association between volumetric information of 4'-[methyl-C]thiothymidine (4DST) positron emission tomography (PET) and fluid-attenuated inversion recovery (FLAIR) and T1-weighted gadopentetate dimeglumine (Gd)-enhanced magnetic resonance imaging (MRI), in patients with newly diagnosed glioma.

Methods: A total of 23 patients with newly diagnosed glioma who underwent both 4DST PET/CT and Gd-enhanced MRI before therapy were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Results: This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.

Interim 4'-[methyl-C]-thiothymidine PET for predicting the chemoradiotherapeutic response in head and neck squamous cell carcinoma: comparison with [F]FDG PET.

Purpose: We investigated the potential of interim 4'-[methyl-C]thiothymidine ([C]4DST) PET for predicting the chemoradiotherapeutic response for head and neck squamous cell carcinoma (HNSCC), in comparison with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) PET.

Methods: A total of 32 patients with HNSCC who underwent both [C]4DST and [F]FDG PET/CT before therapy (baseline) and at approximately 40 Gy point during chemoradiotherapy (interim) were available for a retrospective analysis of prospectively collected data. The baseline was treatment-naïve PET/CT scan as part of staging.