Abstract Purpose To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers. Methods We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software. Results All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq. Conclusion We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731. Trial registration ClinicalTrials.gov, NCT03539731 (registered 28 May 2018)

Glioma treatment planning requires precise tumor delineation, which is typically performed with contrast-enhanced (CE) MRI. However, CE MRI fails to reflect the entire extent of glioma. O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET may detect tumor volumes missed by CE MRI. We investigated the clinical value of simultaneous FET-PET and CE MRI in delineating tumor extent before treatment planning. Guided stereotactic biopsy was used to validate the findings.

To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT.

Abstract Purpose The aim of our study was to comprehensively evaluate the most valuable metabolic parameters of cervical tumours and pelvic lymph nodes (PLN) by FDG-PET/CT to predict para-aortic lymph node (PALN) metastasis and stratify patients for surgical staging. Methods The study included patients with locally advanced cervical cancer, negative PALN uptake on preoperative FDG-PET/CT, and para-aortic lymphadenectomy. Two senior nuclear medicine physicians expert in gynaecologic oncology reviewed all PET/CT exams, and extracted tumour SUVmax, MTV, and TLG, as well as PLN. Prognostic parameters of PALN involvement were identified using ROC curves and logistic regression analysis. Results One hundred and twenty-five consecutive locally advanced cervical cancer patients were included. The FDG-PET/CT false-negative rate was, respectively, 27.7% (13/47) and 5.1% (4/78) in patients with and without FDG-PET/CT PLN uptake. The AUC of cervical tumour size, SUVmax, MTV, and TLG was, respectively, 0.75 (0.62–0.87), 0.59 (0.44–0.76), 0.75 (0.60–0.90), and 0.71 (0.56–0.86). The AUC of PLN size, SUVmax, SUVmean, PLN SUVmax/Tumour SUVmax ratio, MTV, and TLG was, respectively, 0.57 (0.37–0.78), 0.82 (0.68–0.95), 0.77 (0.61–0.94), 0.85 (0.72–0.98), 0.69 (0.51–0.87), and 0.74 (0.57–0.91). The metabolic parameter showing the best trade-off between sensitivity and specificity to predict PALN involvement was the ratio between PLN and tumour SUVmax. Conclusion The risk of PALN metastasis in FDG-PET/CT negative PLN patients is very low, so para-aortic lymphadenectomy does not seem justified. In patients with preoperative PLN uptake on FDG-PET/CT, surgical staging led to treatment modification in more than 25% of cases and should therefore be performed. Patients with more than one positive PLN and high PLN metabolic activity are at high risk of para-aortic extension and recurrence. Further prospective evaluation is required to consider intensified treatment modalities without prior PALN dissection.

The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline.

68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear.

Basal/acetazolamide brain perfusion single-photon emission computed tomography (SPECT) has been used to evaluate functional hemodynamics in patients with carotid artery stenosis. We aimed to develop a deep learning model as a support system for interpreting brain perfusion SPECT leveraging unstructured text reports.

177Lu-DOTATATE targeting the somatostatin receptor (SSTR) is utilized for treatment of neuroendocrine tumors (NETs). Onalespib, a heat shock protein 90 (HSP90) inhibitor, has demonstrated radiosensitizing properties and may thus enhance the effect of 177Lu-DOTATATE. Consequently, the aim of this study was to assess the potential of Onalespib in combination with 177Lu-DOTATATE in vivo and to examine the toxicity profiles of the treatments.

Abstract Purpose The aim of this study was to investigate if the etiologic classification of infantile spasm (IS) using positron emission tomography/magnetic resonance imaging (PET/MR) is feasible. Based on the classified etiologic groups, we further evaluated the efficacy of adrenocorticotropic hormone (ACTH) therapy in different IS groups. Materials and methods One hundred fifty-five children diagnosed with IS were included in this study. A qualitative assessment of the PET/MR images was performed. The abnormal lesions localized with both MR and PET images were considered to be epileptic foci, and the patients with these lesions were classified into the structural-metabolic group. For the remaining patients, quantitative analyses were further performed on whole-brain T1-weighted (T1WI) and PET images, based on the asymmetry index of bilateral volumes and metabolic quantifications. Patients with asymmetry indices above a certain threshold (15%) were classified into the structural-metabolic group. The patients without positive finding from either qualitative or quantitative analyses were assigned to the unknown etiology group. The efficacy of ACTH therapy was evaluated in the different IS groups. Results Among the 155 children with IS, 18 genetic cases were first diagnosed by the genetic testing. In the remaining 137 cases, 49 cases were identified with structural-metabolic etiology using qualitative PET/MR assessments. Fifty-two cases were newly diagnosed with quantitative analysis. The remaining 36 cases were classified into the unknown etiology group. The efficacy of ACTH therapy was statistically different for the different etiology groups (p < 0.001). The respective efficacy rates for the genetic, qualitative structural-metabolic, quantitative structural-metabolic, and unknown etiology groups were 27.8% (5/18), 30.61% (15/49), 34.62% (18/52), and 72.22% (26/36), respectively. Conclusions The combination of PET and MR provides additional diagnostic information for IS. Quantitative analysis can further improve patient etiologic classifications and the predication of therapy efficacies.

Abstract Purpose Integrin αvβ6 belongs to the RGD subset of the integrin family, and its expression levels are a prognostic and theranostic factor in some types of cancer and pulmonary fibrosis. This paper describes the GMP radiolabelling of the synthetic 20 amino acid peptide A20FMDV2 (NAVPNLRGDLQVLAQKVART), derived from the foot-and-mouth disease virus, and characterises the use of [18F]FB-A20FMDV2 as a high affinity, specific and selective PET radioligand for the quantitation and visualisation of αvβ6 in rodent lung to support human translational studies. Methods The synthesis of [18F]FB-A20FMDV2 was performed using a fully automated and GMP-compliant process. Sprague-Dawley rats were used to perform homologous (unlabelled FB-A20FMDV2) and heterologous (anti-αvβ6 antibody 8G6) blocking studies. In order to generate a dosimetry estimate, tissue residence times were generated, and associated tissue exposure and effective dose were calculated using the Organ Level Internal Dose Assessment/Exponential Modelling (OLINDA/EXM) software. Results [18F]FB-A20FMDV2 synthesis was accomplished in 180 min providing ~800 MBq of [18F]FB-A20FMDV2 with a molar activity of up to 150 GBq/μmol and high radiochemical purity (> 97%). Following i.v. administration to rats, [18F]FB-A20FMDV2 was rapidly metabolised with intact radiotracer representing 5% of the total radioactivity present in rat plasma at 30 min. For the homologous and heterologous block in rats, lung-to-heart SUV ratios at 30–60 min post-administration of [18F]FB-A20FMDV2 were reduced by 38.9 ± 6.9% and 56 ± 19.2% for homologous and heterologous block, respectively. Rodent biodistribution and dosimetry calculations using OLINDA/EXM provided a whole body effective dose in humans 33.5 μSv/MBq. Conclusion [18F]FB-A20FMDV2 represents a specific and selective PET ligand to measure drug-associated αvβ6 integrin occupancy in lung. The effective dose, extrapolated from rodent data, is in line with typical values for compounds labelled with fluorine-18 and combined with the novel fully automated and GMP-compliant synthesis and allows for clinical use in translational studies.

Abstract Purpose To explore the relationship between [18F]fluorodeoxyglucose (18F-FDG uptake) and PD-L1 expression and determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in tumour cells (TCs) and tumour-infiltrating immune cells (TIICs) in patients with nasopharyngeal carcinoma (NPC). Methods We retrospectively evaluated the records of 84 eligible patients who received an initial histopathological diagnosis of NPC between December 2016 and March 2019. All tissue specimens and PET/CT images were collected prior to treatment. High PD-L1 expression in TCs and TIICs was defined as ≥ 50% of stained cells. Results There was a significant difference in 18F-FDG uptake according to the PD-L1 status in TCs and TIICs. Univariate analysis showed that PD-L1 expression in TCs was associated with tumour maximum standardized uptake value (SUVmax) (P < 0.001), primary tumour total lesion glycolysis (TLG; P < 0.001), and T stage (P = 0.044), but not with plasma Epstein-Barr virus (EBV) load (P = 0.816), whereas PD-L1 expression in TIICs was related to SUVmax (P = 0.011), TLG (P = 0.001), T stage (P = 0.028), and plasma EBV load (P = 0.003). In multivariate logistic regression, PD-L1 expression in TCs was positively associated with SUVmax (P = 0.003) and TLG (P = 0.001), and in TIICs, negatively associated with SUVmax (P = 0.038) and plasma EBV load (P = 0.025). Conclusions 18F-FDG uptake in NPC lesions was positively correlated with PD-L1 expression in TCs and negatively correlated with PD-L1 expression in TIICs. Thus, 18F-FDG PET/CT may be useful for evaluating the PD-L1 status in patients with NPC.

Our study intended to explore the association between combining 18F–FDG PET/CT metabolic parameters and other clinical features and anaplastic lymphoma kinase (ALK) or c-ros oncogene 1 (ROS1) fusion in non-small-cell lung cancer (NSCLC).

There is preliminary evidence for prostate-specific membrane antigen (PSMA) upregulation effects of androgen receptor blockade in prostate cancer. In an attempt to find the best condition for PSMA radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC) patients, we evaluated the effect of oral enzalutamide in patients, predominantly having previously progressed on enzalutamide treatment.

The role that gut microbiota plays in determining the efficacy of the anti-tumor effect of immune checkpoint inhibitors is gaining increasing attention, and fecal bacterial transplantation has been recognized as a promising strategy for improving or rescuing the effect of immune checkpoint inhibition. However, techniques for the precise monitoring of in vivo bacterial behaviors after transplantation are limited. In this study, we aimed to use metabolic labeling and subsequent positron emission tomography (PET) imaging to track the in vivo behaviors of gut bacteria that are responsible for the efficacy of anti-PD-1 therapy in living mice.

Abstract Purpose 18F-sodium fluoride (18F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity – such as maximum target to background ratio (TBRmax) – are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA]). Methods Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18F-NaF PET and coronary CT angiography. We assessed the association between coronary 18F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume. Results In 50 patients (64% males, 63 ± 7 years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3–98.1)% versus 58.6 (44.9–71.4)% and a specificity of 95.7 (88.0–99.1)% versus 80.0 (68.7–88.6)% (both p < 0.001). 18F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001). Conclusions Automated assessment of disease activity across the entire coronary vasculature is feasible using 18F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

Abstract Purpose 18F-Sodium fluoride (18F-NaF) positron emission tomography (PET) has the potential to detect high-risk coronary plaques. Epicardial adipose tissue (EAT) reportedly correlates with coronary atherosclerosis progression. We evaluated the relationship between coronary arterial 18F-NaF uptake and EAT findings using computed tomography (CT). Methods We studied 40 patients with ≥ 1 coronary plaque detected on cardiac CT who underwent 18F-NaF PET/CT. EAT volume was measured using CT and indexed to body surface area in each patient. Each plaque was evaluated for CT-based luminal stenosis and high-risk features. The mean EAT density surrounding each plaque was calculated as perilesional EAT density (PLED) using non-contrast CT images. Focal 18F-NaF uptake in each plaque was quantified using the maximum tissue-to-background ratio (TBRmax). Results EAT volume index was similar between patients with TBRmax ≥ 1.28 (previously reported optimal cutoff to predict coronary events) and those with lower TBRmax, but patients with TBRmax ≥ 1.28 showed higher maximum PLED per patient (− 86 ± 12 Hounsfield units (HU) versus − 98 ± 11 HU, P = 0.0044). In the lesion-based analysis (n = 92), PLED was positively correlated with TBRmax, and the optimal PLED cutoff to identify TBRmax ≥ 1.28 was − 97 HU. On multivariate analysis adjusted for lesion location, obstructive stenosis, and high-risk plaque on CT, PLED ≥ − 97 HU remained a significant predictor of TBRmax ≥ 1.28. Conclusions Increased PLED was associated with significant coronary arterial 18F-NaF uptake. Step-by-step analyses of EAT density on CT and coronary arterial 18F-NaF uptake on PET may offer novel strategies for risk prediction in coronary artery disease.

Abstract Background Impulse control disorders (ICD) are a common and disrupting complication of Parkinson’s disease (PD) treatment. Although their relationship with dopaminergic activity is well studied, their brain metabolic correlates are mostly unknown. Methods In this work we studied brain metabolism using brain 18F-FDG-PET. We performed a case-control study nested within a cohort of PD patients free of ICD at baseline to compare ICD patients right after ICD diagnosis and prior to any treatment modification with matched ICD-free patients. We also compared both PD groups with healthy controls. Results When compared with ICD-free PD patients, PD patients with recently diagnosed ICD showed higher glucose metabolism in widespread areas comprising prefrontal cortices, both amygdalae and default mode network hubs (p < 0.05, corrected). When compared to healthy controls, they did not show hypermetabolism, and the only hypometabolic region was the right caudate. In turn, ICD-free patients showed diffuse hypometabolism when compared to healthy controls. Conclusion Our results suggest brain metabolism is more preserved in PD patients with ICD than patients without ICD. This metabolic preservation could be related to ICD development.

Abstract Purpose This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts. Methods A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected. Results Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer. Conclusions SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine-99mTc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach.

The article 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors written by Laure Michaud, B. J. Beattie, T. Akhurst, M. Dunphy, P. Zanzonico, R. Finn, A. Mauguen, H. Schöder, W. A. Weber, A. B. Lassman, R. Blasberg.

We present a 62-year-old woman who, after a catarrhal episode, underwent a chest xray and a chest CT, identifying a pleural-based mass in the left lower lobe. This lesion presented a mixed pattern with solid and peripheral ground-glass attenuation, and an air-bronchogram sign. Despite de suspicion of bronchopneumonia, a lung neoplasm like a predominantly lepidic adenocarcinoma could not be ruled. A 18 F-FDG PET/CT showed a focal radiotracer uptake with SUVmax of 5.34 in the pulmonary lesion, supporting the neoplastic etiology. Consequently, a lower lobectomy was performed and histological examination concluded that the final diagnosis was a B lymphoid hyperplasia-type Castleman disease. Castleman’s disease is an uncommon disorder that can be easily misdiagnosed as lymphoma, neoplasm or infection. Unicentric Castleman’s disease (UCD) usually presents a hyaline-vascular histological subtype and is usually asymptomatic. Extranodal involvement is very rare. Only a few cases of solid organ involvement such us spleen or parotid gland have been described. UCD originating in the lung is extremely rare and should be considered in the differential diagnosis of a primary pulmonary malignant tumor.

The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure.

Clinical outcomes of patients with resected oral cavity squamous cell carcinoma (OCSCC) chiefly depend on the presence of specific clinicopathological risk factors (RFs). Here, we performed a combined analysis of FDG-PET, genetic markers, and clinicopathological RFs in an effort to improve prognostic stratification.

Medullary thyroid carcinoma (MTC) is a malignant tumour derived from the para-follicular thyroid C cells. It may occur in sporadic or hereditary forms and surgery represent the primary cure.

The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA I&T) PET/CT performed in newly diagnosed, treatment-naïve prostate cancer (PCa) patients prior to definitive treatment.

68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC.

To summarise data with radium-223 dichloride (223RaCl2), a mechanism-mediated targeted alpha therapy (TAT), in metastatic castration-resistant prostate cancer (mCRPC) and to chart the development of TAT in mCRPC and in other tumour types.

Radiomics in nuclear medicine is rapidly expanding. Reproducibility of radiomics studies in multicentre settings is an important criterion for clinical translation. We therefore performed a meta-analysis to investigate reproducibility of radiomics biomarkers in PET imaging and to obtain quantitative information regarding their sensitivity to variations in various imaging and radiomics-related factors as well as their inherent sensitivity. Additionally, we identify and describe data analysis pitfalls that affect the reproducibility and generalizability of radiomics studies. After a systematic literature search, 42 studies were included in the qualitative synthesis, and data from 21 were used for the quantitative meta-analysis. Data concerning measurement agreement and reliability were collected for 21 of 38 different factors associated with image acquisition, reconstruction, segmentation and radiomics-specific processing steps. Variations in voxel size, segmentation and several reconstruction parameters strongly affected reproducibility, but the level of evidence remained weak. Based on the meta-analysis, we also assessed inherent sensitivity to variations of 110 PET image biomarkers. SUVmean and SUVmax were found to be reliable, whereas image biomarkers based on the neighbourhood grey tone difference matrix and most biomarkers based on the size zone matrix were found to be highly sensitive to variations, and should be used with care in multicentre settings. Lastly, we identify 11 data analysis pitfalls. These pitfalls concern model validation and information leakage during model development, but also relate to reporting and the software used for data analysis. Avoiding such pitfalls is essential for minimizing bias in the results and to enable reproduction and validation of radiomics studies.

Neuroinflammation, as defined by the activation of microglia and astrocytes, has emerged in the last years as a key element of the pathogenesis of neurodegenerative diseases based on genetic findings and preclinical and human studies. This has raised the need for new methodologies to assess and follow glial activation in patients, prompting the development of PET ligands for molecular imaging of glial cells and novel structural MRI and DTI tools leading to a multimodal approach. The present review describes the recent advancements in microglia and astrocyte biology in the context of health, ageing, and Alzheimer’s disease, the most common dementia worldwide. The review further delves in molecular imaging discussing the challenges associated with past and present targets, including conflicting findings, and finally, presenting novel methodologies currently explored to improve our in vivo knowledge of the neuroinflammatory patterns in Alzheimer’s disease. With glial cell activation as a potential therapeutic target in neurodegenerative diseases, the translational research between cell biologists, chemists, physicists, radiologists, and neurologists should be strengthened.

This study investigated the potential of deep convolutional neural networks (CNN) for automatic classification of FP-CIT SPECT in multi-site or multi-camera settings with variable image characteristics.

While molecular imaging with positron emission tomography or single-photon emission computed tomography already reports on tumour molecular mechanisms on a macroscopic scale, there is increasing evidence that there are multiple additional features within medical images that can further improve tumour characterization, treatment prediction and prognostication. Early reports have already revealed the power of radiomics to personalize and improve patient management and outcomes. What remains unclear is how these additional metrics relate to underlying molecular mechanisms of disease. Furthermore, the ability to deal with increasingly large amounts of data from medical images and beyond in a rapid, reproducible and transparent manner is essential for future clinical practice. Here, artificial intelligence (AI) may have an impact. AI encompasses a broad range of ‘intelligent’ functions performed by computers, including language processing, knowledge representation, problem solving and planning. While rule-based algorithms, e.g. computer-aided diagnosis, have been in use for medical imaging since the 1990s, the resurgent interest in AI is related to improvements in computing power and advances in machine learning (ML). In this review we consider why molecular and cellular processes are of interest and which processes have already been exposed to AI and ML methods as reported in the literature. Non-small-cell lung cancer is used as an exemplar and the focus of this review as the most common tumour type in which AI and ML approaches have been tested and to illustrate some of the concepts.

Our understanding on human neurodegenerative disease was previously limited to clinical data and inferences about the underlying pathology based on histopathological examination. Animal models and in vitro experiments have provided evidence for a cell-autonomous and a non-cell-autonomous mechanism for the accumulation of neuropathology. Combining modern neuroimaging tools to identify distinct neural networks (connectomics) with target-specific positron emission tomography (PET) tracers is an emerging and vibrant field of research with the potential to examine the contributions of cell-autonomous and non-cell-autonomous mechanisms to the spread of pathology. The evidence provided here suggests that both cell-autonomous and non-cell-autonomous processes relate to the observed in vivo characteristics of protein pathology and neurodegeneration across the disease spectrum. We propose a synergistic model of cell-autonomous and non-cell-autonomous accounts that integrates the most critical factors (i.e., protein strain, susceptible cell feature and connectome) contributing to the development of neuronal dysfunction and in turn produces the observed clinical phenotypes. We believe that a timely and longitudinal pursuit of such research programs will greatly advance our understanding of the complex mechanisms driving human neurodegenerative diseases.

The high false positive rate (FPR) of 18F-FDG PET/CT in lung cancer screening represents a severe challenge for clinical decision-making. This study aimed to develop a clinical-translatable radiomics nomogram for reducing the FPR of PET/CT in lung cancer diagnosis, and to determine the impact of integrating manual diagnosis to the performance of the radiomics nomogram.

Artificial intelligence (AI) is currently regaining enormous interest due to the success of machine learning (ML), and in particular deep learning (DL). Image analysis, and thus radiomics, strongly benefits from this research. However, effectively and efficiently integrating diverse clinical, imaging, and molecular profile data is necessary to understand complex diseases, and to achieve accurate diagnosis in order to provide the best possible treatment. In addition to the need for sufficient computing resources, suitable algorithms, models, and data infrastructure, three important aspects are often neglected: (1) the need for multiple independent, sufficiently large and, above all, high-quality data sets; (2) the need for domain knowledge and ontologies; and (3) the requirement for multiple networks that provide relevant relationships among biological entities. While one will always get results out of high-dimensional data, all three aspects are essential to provide robust training and validation of ML models, to provide explainable hypotheses and results, and to achieve the necessary trust in AI and confidence for clinical applications.

Techniques from the field of artificial intelligence, and more specifically machine (deep) learning methods, have been core components of most recent developments in the field of medical imaging. They are already being exploited or are being considered to tackle most tasks, including image reconstruction, processing (denoising, segmentation), analysis and predictive modelling. In this review we introduce and define these key concepts and discuss how the techniques from this field can be applied to nuclear medicine imaging applications with a particular focus on radio(geno)mics.

Quantitative PET/MR imaging is challenged by the accuracy of synthetic CT (sCT) generation from MR images. Deep learning-based algorithms have recently gained momentum for a number of medical image analysis applications. In this work, a novel sCT generation algorithm based on deep learning adversarial semantic structure (DL-AdvSS) is proposed for MRI-guided attenuation correction in brain PET/MRI.

To determine whether [18F]FDG PET/CT-derived radiomic features alone or in combination with clinical, laboratory and biological parameters are predictive of 2-year progression-free survival (PFS) in patients with mantle cell lymphoma (MCL), and whether they enable outcome prognostication.

Image quality of positron emission tomography (PET) is limited by various physical degradation factors. Our study aims to perform PET image denoising by utilizing prior information from the same patient. The proposed method is based on unsupervised deep learning, where no training pairs are needed.

Radiomics, machine learning, and, more generally, artificial intelligence (AI) provide unique tools to improve the performances of nuclear medicine in all aspects. They may help rationalise the operational organisation of imaging departments, optimise resource allocations, and improve image quality while decreasing radiation exposure and maintaining qualitative accuracy. There is already convincing data that show AI detection, and interpretation algorithms can perform with equal or higher diagnostic accuracy in various specific indications than experts in the field. Preliminary data strongly suggest that AI will be able to process imaging data and information well beyond what is visible to the human eye, and it will be able to integrate features to provide signatures that may further drive personalised medicine. As exciting as these prospects are, they currently remain essentially projects with a long way to go before full validation and routine clinical implementation. AI uses a language that is totally unfamiliar to nuclear medicine physicians, who have not been trained to manage the highly complex concepts that rely primarily on mathematics, computer sciences, and engineering. Nuclear medicine physicians are mostly familiar with biology, pharmacology, and physics, yet, considering the disruptive nature of AI in medicine, we need to start acquiring the knowledge that will keep us in the position of being actors and not merely witnesses of the wonders developed by other stakeholders in front of our incredulous eyes. This will allow us to remain a useful and valid interface between the image, the data, and the patients and free us to pursue other, one might say nobler tasks, such as treating, caring and communicating with our patients or conducting research and development.

Almost 50 million people worldwide are affected by Alzheimer’s disease (AD), the most common neurodegenerative disorder. Development of disease-modifying therapies would benefit from reliable, non-invasive positron emission tomography (PET) biomarkers for early diagnosis, monitoring of disease progression, and assessment of therapeutic effects. Traditionally, PET ligands have been based on small molecules that, with the right properties, can penetrate the blood–brain barrier (BBB) and visualize targets in the brain. Recently a new class of PET ligands based on antibodies have emerged, mainly in applications related to cancer. While antibodies have advantages such as high specificity and affinity, their passage across the BBB is limited. Thus, to be used as brain PET ligands, antibodies need to be modified for active transport into the brain. Here, we review the development of radioligands based on antibodies for visualization of intrabrain targets. We focus on antibodies modified into a bispecific format, with the capacity to undergo transferrin receptor 1 (TfR1)-mediated transcytosis to enter the brain and access pathological proteins, e.g. amyloid-beta. A number of such antibody ligands have been developed, displaying differences in brain uptake, pharmacokinetics, and ability to bind and visualize the target in the brain of transgenic mice. Potential pathological changes related to neurodegeneration, e.g. misfolded proteins and neuroinflammation, are suggested as future targets for this novel type of radioligand. Challenges are also discussed, such as the temporal match of radionuclide half-life with the ligand’s pharmacokinetic profile and translation to human use. In conclusion, brain PET imaging using bispecific antibodies, modified for receptor-mediated transcytosis across the BBB, is a promising method for specifically visualizing molecules in the brain that are difficult to target with traditional small molecule ligands.

The quantitative imaging features (radiomics) that can be obtained from the different modalities of current-generation hybrid imaging can give complementary information with regard to the tumour environment, as they measure different morphologic and functional imaging properties. These multi-parametric image descriptors can be combined with artificial intelligence applications into predictive models. It is now the time for hybrid PET/CT and PET/MRI to take the advantage offered by radiomics to assess the added clinical benefit of using multi-parametric models for the personalized diagnosis and prognosis of different disease phenotypes.

Detection of residual or recurrent vital renal tumor on follow-up (FU) cross-sectional imaging after ablative therapy is challenging. The specific and high expression levels of carbonic anhydrase IX (CAIX) in clear cell renal cell carcinoma (ccRCC) makes it a suitable target for imaging using radiolabeled anti-CAIX antibody girentuximab. The objective of this study was to evaluate the feasibility of targeted FU imaging 1 month after cryoablation of ccRCC using single photon emission computed tomography (SPECT) after 111In-labeled girentuximab administration.

Although functional brain imaging has been used for the early and objective assessment of cognitive dysfunction, there is a lack of generalized image-based biomarker which can evaluate individual’s cognitive dysfunction in various disorders. To this end, we developed a deep learning-based cognitive signature of FDG brain PET adaptable for Parkinson’s disease (PD) as well as Alzheimer’s disease (AD).

In Parkinson’s disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP).

This prospective study aimed (1) to assess the non-small cell lung cancer (NSCLC) evolutive patterns to immunotherapy using FDG-PET and (2) to describe their association with clinical outcome.

Prognostic significance of volumetric 18F-fluorodeoxyglucose (FDG) positron emission tomography/computer tomography (PET/CT) parameters in carbon-ion radiotherapy (C-ion RT) treated stage I non-small cell lung cancer, and need of histology-wise separate cut-off values for risk stratification were assessed.

Meningiomas have an excellent survival prognosis, and radiotherapy (RT) is a central component of interdisciplinary treatment. During treatment planning, the definition of the target volume remains challenging using MR and CT imaging alone. This is the first study to analyze the impact of additional PET-imaging on local control (LC) and overall survival (OS) after high-precision RT.

Recently, the new hybrid chelator DATA (6-amino-1,4-diazepine-triacetate) has been introduced, which has the advantage of high yield and radiolabelling of DATA-based octreotide derivative (TOC) at room temperature in contrast to tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) that needs 95 °C for effective labelling. However, the diagnostic potential of DATA-TOC has not been studied with other chelators in humans. The aim of this study was to compare the diagnostic efficacy of [68Ga]Ga-DATA-TOC with [68Ga]Ga-DOTA-NOC (which is the current standard for imaging neuroendocrine tumours (NET)) in patients of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to 177Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter 225Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients’ quality-of-life. We hypothesized that when 177Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity 225Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity.

Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both upregulated in tumor-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib.

We aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).

In Y90 radioembolization, the number of microspheres infused varies by more than a factor of 20 over the shelf-life of the glass radioembolization device. We investigated the effect of the number of Y90 microspheres on normal liver tissue.

This study aims to reveal the feasibility and potential of molecular connectivity based on neurotransmission in comparison with the metabolic connectivity with an application to dopaminergic pathways. For this purpose, we propose to compare the neurotransmission connectivity findings using 123I-FP-CIT SPECT and 18F-FDOPA PET with the metabolic connectivity findings using 18F-FDG PET.

We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy.

To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention.

OTS514 is a highly specific inhibitor targeting lymphokine-activated killer T cell-originated protein kinase (TOPK). A fluorescently labeled TOPK inhibitor could be used for tumor delineation or intraoperative imaging, potentially improving patient care.

To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate-specific membrane antigen (PSMA) tracer uptake demonstrated in 68Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer (PC) patients.

The author names of the original version of this article were inadvertently interchanged. Correct author names are presented here.

Diagnosis of spinal infection (SI) is challenging and usually requires multiple tests. We aimed to perform a systematic review and a bivariate meta-analysis on the diagnostic role of 18F-FDG PET/CT in patients with SI.

Artificial intelligence involves a wide range of smart techniques that are applicable to medical services including nuclear medicine. Recent advances in computer power, availability of accumulated digital archives containing large amount of patient images, and records bring new opportunities for the implementation of artificial techniques in nuclear medicine. As a subset of artificial intelligence, machine learning is an emerging tool that possibly perform many clinical tasks. Nuclear medicine community needs to adapt to this fast approaching smart era, to exploit the opportunities and tackle the problems associated with artificial intelligence tools. It is aimed in this editorial to outline the potentials and challenges of artificial intelligence applications in nuclear medicine.

Multidrug resistance (MDR) impedes cancer treatment. Two efflux transporters from the ATP-binding cassette (ABC) family, ABCB1 and ABCG2, may contribute to MDR by restricting the entry of therapeutic drugs into tumor cells. Although a higher expression of these transporters has been correlated with an unfavorable response to chemotherapy, transporter expression does not necessarily correlate with function. In this study, we characterized the pharmacological properties of [18F]AVT-011, a new PET radiotracer for imaging transporter-mediated MDR in tumors.