Initial clinical experience using 68Ga-FAPI-46 PET/CT for detecting various cancer types.

OBJECTIVE: Numerous studies have shown that gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) scans would yield high intra-tumoral tracer uptake and low uptake in normal tissues as background, thus allowing for excellent visualization of lesions in the cancer microenvironment. This study set out to compare the suitability of novel 68Ga-FAPI-46 PET versus routine fluorine-18-fluorodeoxyglucose (18F-FDG) PET and other few cases of 68Ga-DOTATATE/68Ga-Pentixafor PET/CT for the assessment of different types of cancer. SUBJECTS AND METHODS: A retrospective analysis of 11 patients (6 males, 5 females; average age: 53 years, range: 10-58 years) with histopathologically confirmed, well-differentiated adenocarcinoma, medullar thyroid cancer (MTC), papillary thyroid carcinoma (PTC), cervical, gastric, glioblastoma multiform (GBM), colon, Ewing's sarcoma, and breast cancer was performed. These patients underwent PET/CT scans using four different radiotracers (9 18F-FDG, 11 68Ga- FAPI, 3 68Ga-DOTATATE, and 1 68Ga-Pentixafor). The patients' PET/CT images were visually evaluated for cancer detection, and analyzed semi-quantitatively through image- derived metrics, such as target-to-background ratio (TBR) and maximum standardized uptake value (SUVmax), for recurrence and metastasis. RESULTS: The study of 11 patients revealed that 68Ga-FAPI-46 was more effective than other tracers for detecting metastases, with 55 vs. 49 metastases in the lymph nodes, 4 vs. 3 in the liver, and 4 vs. 3 in the bones detected in comparison to 18F-FDG. No significant differences were observed in 68Ga-DOTATATE and 68Ga-Pentixafor PET images. In addition, in five patients, the SUVmax and TBR values in 68Ga-FAPI-46 PET images were significantly higher than those in 18F-FDG PET images for lymph nodes and bone metastases. Although the SUVmax in 68Ga-FAPI-46 and 18F-FDG PET images for liver metastases was comparable, 68Ga-FAPI- 46 had a significantly higher TBR than 18F-FDG. CONCLUSION: Our findings suggest that FAPI PET/CT is not suitable for evaluating GBM and Ewing sarcoma but generally outperforms 18F-FDG PET/CT in various types of breast cancer, gastrointestinal, gynecological, PTC and MTC. However, larger trials are needed to validate these preliminary findings.

Positron Emission Tomography Molecular Imaging of the Major Neurodegenerative Disorders: Overview and Pictorial Essay, from a Nuclear Medicine Center's Perspective.

Computed tomography (CT) and magnetic resonance imaging (MRI) provide key structural information on brain pathophysiology. Positron emission tomography (PET) measures metabolism in the living brain; it plays an important role in molecular neuroimaging and is rapidly expanding its field of application to the study of neurodegenerative diseases. Different PET radiopharmaceuticals allow in vivo characterization and quantization of biological processes at the molecular and cellular levels, from which many neurodegenerative diseases develop. In addition, hybrid imaging tools such as PET/CT and PET/MRI support the utility of PET, enabling the anatomical mapping of functional data. In this overview, we describe the most commonly used PET tracers in the diagnostic work-up of patients with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. We also briefly discuss the pathophysiological processes of tracer uptake in the brain, detailing their specific cellular pathways in clinical cases. This overview is limited to imaging agents already applied in human subjects, with particular emphasis on those tracers used in our department.

Novel Approaches in Molecular Imaging and Neuroimaging of Fibromyalgia.

Fibromyalgia (FM) represents a condition that is still controversial in its entity, pathophysiology, diagnosis and management. The aim of this review is to focus on imaging aspects of FM, especially on novel approaches in molecular imaging, with a special focus on neuroimaging. Novel functional and molecular imaging findings may represent, eventually, future biomarkers both in research settings and in terms of clinical practice. Several imaging techniques have already been tested in clinical trials in the FM field, including functional MRI, positron emission tomography (PET) imaging with 18F-FDG in FM, PET imaging of the dopaminergic system, PET imaging of the GABAergic system, PET imaging with neuroinflammation and neuroimmune parameters, PET imaging of the opioid system and H215O-PET activation studies. Therefore, the potential role in the FM field of fMRI and different PET tracers has been discussed in different settings, serving as a comprehensive guide of novel imaging options both in research and in the clinical field.

Tau Biomarkers in Dementia: Positron Emission Tomography Radiopharmaceuticals in Tauopathy Assessment and Future Perspective.

Abnormal accumulation of Tau protein is closely associated with neurodegeneration and cognitive impairment and it is a biomarker of neurodegeneration in the dementia field, especially in Alzheimer's disease (AD); therefore, it is crucial to be able to assess the Tau deposits in vivo. Beyond the fluid biomarkers of tauopathy described in this review in relationship with the brain glucose metabolic patterns, this review aims to focus on tauopathy assessment by using Tau PET imaging. In recent years, several first-generation Tau PET tracers have been developed and applied in the dementia field. Common limitations of first-generation tracers include off-target binding and subcortical white-matter uptake; therefore, several institutions are working on developing second-generation Tau tracers. The increasing knowledge about the distribution of first- and second-generation Tau PET tracers in the brain may support physicians with Tau PET data interpretation, both in the research and in the clinical field, but an updated description of differences in distribution patterns among different Tau tracers, and in different clinical conditions, has not been reported yet. We provide an overview of first- and second-generation tracers used in ongoing clinical trials, also describing the differences and the properties of novel tracers, with a special focus on the distribution patterns of different Tau tracers. We also describe the distribution patterns of Tau tracers in AD, in atypical AD, and further neurodegenerative diseases in the dementia field.

MGMT Promoter Methylation and IDH1 Mutations Do Not Affect [18F]FDOPA Uptake in Primary Brain Tumors.

The aim of our study was to investigate the effects of methylation of O6-methylguanine-DNA methyltransferase promoter (MGMTp) and isocitrate dehydrogenase 1 (IDH 1) mutations on amino acid metabolism evaluated with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). Seventy-two patients with primary brain tumors were enrolled in the study (33 women and 39 men; mean age 44 ± 12 years old). All of them were subjected to PET/CT examination after surgical treatment. Of them, 29 (40.3%) were affected by grade II glioma and 43 (59.7%) by grade III. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs that of the background. Statistical analysis was performed with the Mann-Whitney U test. Methylation of MGMTp was detectable in 61 out of the 72 patients examinated. Mean SUVr in patients without methylation of MGMTp was 1.44 ± 0,38 vs. 1.35 ± 0.48 of patients with methylation (p = 0.15). Data on IDH1 mutations were available for 43 subjects; of them, 31 are IDH-mutant. Mean SUVr was 1.38 ± 0.51 in patients IDH mutant and 1.46 ± 0.56 in patients IDH wild type. MGMTp methylation and IDH1 mutations do not affect [18F] FDOPA uptake in primary brain tumors and therefore cannot be assessed or predicted by radiopharmaceutical uptake parameters.

Positron Emission Tomography (PET) and Neuroimaging in the Personalized Approach to Neurodegenerative Causes of Dementia.

Generally, dementia should be considered an acquired syndrome, with multiple possible causes, rather than a specific disease in itself. The leading causes of dementia are neurodegenerative and non-neurodegenerative alterations. Nevertheless, the neurodegenerative group of diseases that lead to cognitive impairment and dementia includes multiple possibilities or mixed pathologies with personalized treatment management for each cause, even if Alzheimer's disease is the most common pathology. Therefore, an accurate differential diagnosis is mandatory in order to select the most appropriate therapy approach. The role of personalized assessment in the treatment of dementia is rapidly growing. Neuroimaging is an essential tool for differential diagnosis of multiple causes of dementia and allows a personalized diagnostic and therapeutic protocol based on risk factors that may improve treatment management, especially in early diagnosis during the prodromal stage. The utility of structural and functional imaging could be increased by standardization of acquisition and analysis methods and by the development of algorithms for automated assessment. The aim of this review is to focus on the most commonly used tracers for differential diagnosis in the dementia field. Particularly, we aim to explore 18F Fluorodeoxyglucose (FDG) and amyloid positron emission tomography (PET) imaging in Alzheimer's disease and in other neurodegenerative causes of dementia.

Theragnostic Aspects and Radioimmunotherapy in Pediatric Tumors.

The use of theragnostic radiopharmaceuticals in nuclear medicine has grown rapidly over the years to combine the diagnosis and therapy of tumors. In this review, we performed web-based and desktop literature research to investigate and explain the potential role of theragnostic imaging in pediatric oncology. We focused primarily on patients with aggressive malignancies such as neuroblastoma and brain tumors, to select patients with the highest chance of benefit from personalized therapy. Moreover, the most critical and groundbreaking applications of radioimmunotherapy in children's oncology were examined in this peculiar context. Preliminary results showed the potential feasibility of theragnostic imaging and radioimmunotherapy in pediatric oncology. They revealed advantages in the management of the disease, thereby allowing an intra-personal approach and adding new weapons to conventional therapies.

PET/CT Imaging of Infectious Diseases: Overview of Novel Radiopharmaceuticals.

Infectious diseases represent one of the most common causes of hospital admission worldwide. The diagnostic work-up requires a complex clinical approach, including laboratory data, CT and MRI, other imaging tools, and microbiologic cultures. PET/CT with 18F-FDG can support the clinical diagnosis, allowing visualization of increased glucose metabolism in activated macrophages and monocytes; this tracer presents limits in differentiating between aseptic inflammation and infection. Novel PET radiopharmaceuticals have been developed to overcome these limits; 11C/18F-labeled bacterial agents, several 68Ga-labeled molecules, and white blood cells labeled with 18F-FDG are emerging PET tracers under study, showing interesting preliminary results. The best choice among these tracers can be unclear. This overview aims to discuss the most common diagnostic applications of 18F-FDG PET/CT in infectious diseases and, as a counterpoint, to describe and debate the advantages and peculiarities of the latest PET radiopharmaceuticals in the field of infectious diseases, which will probably improve the diagnosis and prognostic stratification of patients with active infectious diseases.

The Use of Stress Cardiovascular Imaging in Pediatric Population.

Although not frequent in the pediatric population, ischemia could occur in children due to several congenital and acquired disease. Stress imaging is key for the non-invasive evaluation of myocardial abnormalities and perfusion defect in this clinical setting. Moreover, beyond ischemia assessment, it can provide complementary diagnostic and prognostic information in valvular heart disease and cardiomyopathies. When performed using cardiovascular magnetic resonance, it could detect, in addition, myocardial fibrosis and infarction, increasing the diagnostic yield. Several imaging modalities are currently available for the evaluation of stress myocardial perfusion. Advances in technologies have also increased the feasibility, safety and availability of these modalities in the pediatric age group. However, despite the established role of stress imaging and its increasing use in daily clinical practice, there are currently no specific guidelines, and little data are available in the literature on this topic. The aim of this review is to summarize the most recent evidence on pediatric stress imaging and its clinical application with a focus on the advantages and limitations of each imaging modality currently available.

Myocardial Functional Imaging in Pediatric Nuclear Cardiology.

The role of nuclear medicine in pediatric cardiology has grown rapidly over the years, providing useful functional and prognostic information and playing a complementary role to morphological imaging in the evaluation of myocardial perfusion, cardiovascular inflammation and infections, and cardiac sympathetic innervation. The aim of this narrative review is to summarize and highlight the most important evidence on pediatric nuclear cardiology, describing clinical applications and the possibilities, advantages, and limitations of nuclear medicine techniques. Moreover, a special focus will be given to the minimization of radiation exposure in pediatric nuclear cardiology imaging, a critical topic in children.

18F-FDG PET/CT technology for the assessment of brown adipose tissue: an updated review.

INTRODUCTION: This review provides an update of 18 F-fluorodeoxyglucose ([18F] FDG) for Brown adipose tissue (BAT) activity quantification, whose role is not completely understood. AREAS COVERED: We conducted an unstructured search of the literature for any studies employing the [18F] FDG PET in BAT assessment. We explored BAT quantification both in healthy individuals and in different pathologies, after cold exposure and as a metabolic biomarker. The assessment of possible BAT modulators by using [18F] FDG PET is shown. Further PET tracers and novel developments for BAT assessments are also described. EXPERT OPINION: Further PET tracers and imaging modalities are under investigation, but the [18F] FDG PET is currently the method of choice for the evaluation of BAT and further multicentric trials are needed for a better understanding of the BAT physiopathology, also after cold stimuli. The modulation of BAT activity, assessed by [18F] FDG PET imaging, seems a promising tool for the management of conditions such as obesity and type 2 diabetes. Moreover, an interesting possible correlation of BAT activation with prognostic [18F] FDG PET indices in cancer patients should be assessed with further multicentric trials.

Medical Imaging of Inflammations and Infections of Breast Implants.

Breast implants are widely used for reconstructive and/or cosmetic purposes. Inflammations and infections of breast implants represent important complications in clinical practice. The proper management of complications is necessary: diagnostic imaging plays a key role in detecting sites of inflammation and/or infection. The present review aims to illustrate the radiological findings of these conditions with different imaging techniques, such as mammography (MX), ultrasound (US), magnetic resonance imaging (MRI), and nuclear medicine imaging. A knowledge of these findings is essential for radiologists and nuclear medicine physicians to provide helpful information for the clinical management of these complications.

The Role of Multimodality Imaging in Pediatric Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.

The Role of Multimodality Imaging in Patients with Congenital Heart Disease and Infective Endocarditis.

Infective endocarditis (IE) represents an important medical challenge, particularly in patients with congenital heart diseases (CHD). Its early and accurate diagnosis is crucial for effective management to improve patient outcomes. Multimodality imaging is emerging as a powerful tool in the diagnosis and management of IE in CHD patients, offering a comprehensive and integrated approach that enhances diagnostic accuracy and guides therapeutic strategies. This review illustrates the utilities of each single multimodality imaging, including transthoracic and transoesophageal echocardiography, cardiac computed tomography (CCT), cardiovascular magnetic resonance imaging (CMR), and nuclear imaging modalities, in the diagnosis of IE in CHD patients. These imaging techniques provide crucial information about valvular and intracardiac structures, vegetation size and location, abscess formation, and associated complications, helping clinicians make timely and informed decisions. However, each one does have limitations that influence its applicability.

Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects.

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.

Medical Imaging in the Diagnosis of Schistosomiasis: A Review.

Schistosomiasis is one of the most important parasitic diseases and it is endemic in tropical and subtropical areas. Clinical and laboratory data are fundamental for the diagnosis of schistosomiasis, but diagnostic imaging techniques such as x-rays, ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) may be helpful in the evaluation of disease severity and complications. In this context, the aim of this review is to explore the actual role of diagnostic imaging in the diagnosis of schistosomiasis, underlining advantages and drawbacks providing information about the utilization of diagnostic imaging techniques in this context. Furthermore, we aim to provide a useful guide regarding imaging features of schistosomiasis for radiology and nuclear medicine physicians of non-endemic countries: in fact, in the last years non-endemic countries have experienced important flows of migrants from endemic areas, therefore it is not uncommon to face cases of this disease in daily practice.

18F-FDOPA PET/CT SUV-Derived Indices and Volumetric Parameters Correlation in Patients with Primary Brain Tumors.

Novel parameters in PET imaging, such as volumetric parameters, are gaining interest in the scientific literature, but the role of dopaminergic tumor volume (DTV) and total lesion F-DOPA activity (TLDA) and the correlation between volumetric and SUV-derived parameters are not well defined yet. One hundred and thirty-three patients that underwent 18F-FDOPA imaging for primary brain tumors were included in this retrospective study. SUV-derived indices were calculated (the occipital region was chosen to generate ratios of tumor SUV) and compared with volumetric parameters. Regression models were applied in univariate analysis and lnSUVmax was positively associated with lnDTV (beta 0.42, p = 0.007), the lnSUVmax ratio was positively associated with lnDTV (beta 0.80, p = 0.011), lnSUVmax was positively associated with lnTLDA (beta 1.27, p < 0.0001), and the lnSUVmax ratio was positively associated with lnTLDA (beta 1.87, p < 0.0001). Our study demonstrates that volumetric uptake parameters in 18F-FDOPA PET/CT are easier to assess in primary brain tumors with higher SUV max and SUV max ratios, and supports the emerging role of volumetric parameters in the data interpretation.

Peptide Receptor Radionuclide Therapy and Primary Brain Tumors: An Overview.

Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease.

A Rare Case of Pulmonary Schistosomiasis: 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings.

Schistosomiasis is a helminthic infection acquired through direct contact with contaminated fresh water. To the best of our knowledge, this is the first case pulmonary of schistosomias is evaluated with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) reported in the literature. Functional imaging with 18F-FDG PET/CT may help in the diagnosis of schistosomiasis, leading to a correct definition of the disease extension.

Molecular Imaging in Pediatric Brain Tumors.

In the last decade, several radiopharmaceuticals have been developed and investigated for imaging in vivo of pediatric brain tumors with the aim of exploring peculiar metabolic processes as glucose consumption, amino-acid metabolism, and protein synthesis with nuclear medicine techniques. Although the clinical shreds of evidence are limited, preliminary results are encouraging. In this review, we performed web-based and desktop research summarizing the most relevant findings of the literature published to date on this topic. Particular attention was given to the wide spectrum of nuclear medicine advances and trends in pediatric neurooncology and neurosurgery. Furthermore, the role of somatostatin receptor imaging through single-photon emission computed tomography (SPECT) and positron emission tomography (PET) probes, with reference to their potential therapeutic implications, was examined in the peculiar context. Preliminary results show that functional imaging in pediatric brain tumors might lead to significant improvements in terms of diagnostic accuracy and it could be of help in the management of the disease.