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Aim: Tumor markers often remain elevated after intended curative resection of medullary thyroid carcinoma (MTC). The aim of this study was to determine the expression of αvβ3, a promising theranostics target, in MTC and its metastases. Materials & methods: Avβ3 expression was analyzed in 104 patients using a tissue microarray and correlated with clinicopathological variables and survival. Results: Cytoplasmic αvβ3 positivity was seen in 70 patients and was associated with lymph node metastases at time of initial surgery. Membranous positivity was considered positive in 30 patients and was associated with sporadic MTC. Conclusion: Avβ3 was expressed in the cytoplasm of 67% of MTC patients. Membranous expression, which is presumably most relevant for the theranostic use of αvβ3, was seen in 29%. Article highlights After intended curative resection of medullary thyroid carcinoma (MTC), calcitonin levels often remain elevated indicating remnant disease or metastasis. There is a demand for new imaging and therapeutic options for patients with MTC. Avβ3, an integrin expressed in many tumors, is a promising target for nuclear imaging and treatment using radiolabeled arginine-glycine-aspartic acid (RGD). Cytoplasmic and membranous αvβ3 expression was analyzed using a tissue microarray including primary tumors and lymph node metastases of 104 and 27 patients, respectively. Cytoplasmic expression was considered positive in 67% of patients and was associated with lymph node metastases at the time of initial surgery. Membranous expression, which is thought to be most relevant for the theranostic use of αvβ, was seen in 29% of patients and was associated with sporadic MTC. Survival analysis showed no prognostic value of αvβ3. The correlation of immunohistochemical αvβ3 expression and uptake of radiolabeled RGD should be further assessed in patients with membranous αvβ3 expression. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), nanosized lipid bilayer vesicles released by nearly all types of cells, play pivotal roles as intercellular signaling mediators with diverse biological activities. Their adaptability has attracted interest in exploring their role as disease biomarker theranostics. However, the in vivo biodistribution and pharmacokinetic profiles of EVs, particularly following administration into living subjects, remain unclear. Thus, in vivo imaging is vital to enhance our understanding of the homing and retention patterns, blood and tissue half‐life, and excretion pathways of exogenous EVs, thereby advancing real‐time monitoring within biological systems and their therapeutic applications. This review examines state‐of‐the‐art methods including EV labeling with various agents, including optical imaging, magnetic resonance imaging, and nuclear imaging. The strengths and weaknesses of each technique are comprehensively explored, emphasizing their clinical translation. Despite the potential of EVs as cancer theranostics, achieving a thorough understanding of their in vivo behavior is challenging. This review highlights the urgency of addressing current questions in the biology and therapeutic applications of EVs. It underscores the need for continued research to unravel the complexities surrounding EVs and their potential clinical implications. By identifying these challenges, this review contributes to ongoing efforts to optimize EV imaging techniques for clinical use. Ultimately, bridging the gap between research advancements and clinical applications will facilitate the integration of EV‐based theranostics, marking a crucial step toward harnessing the full potential of EVs in medical practice. [ABSTRACT FROM AUTHOR]

In recent years, the application of radionuclides‐containing nanomaterials in cancer treatment has garnered widespread attention. The diversity of nanomaterials allows researchers to selectively combine them with appropriate radionuclides for biomedical purposes, addressing challenges faced by peptides, small molecules, or antibodies used for radionuclide labeling. However, with advantages come challenges, and nanoradionuclides still encounter significant issues during clinical translation. This review summarized the recent progress of nanosized radionuclides for cancer treatment or diagnosis. The discussion began with representative radionuclides and the methods of incorporating them into nanomaterial structures. Subsequently, new combinations of nanomaterials and radionuclides, along with their applications, were introduced to demonstrate their future trends. The benefits of nanoradionuclides included optimized pharmacokinetic properties, enhanced disease‐targeting efficacy, and synergistic application with other treatment techniques. Besides, the basic rule of this section was to summarize how these nanoradionuclides can truly impact the diagnosis and therapy of various cancer types. In the last part, the focus was devoted to the nanoradionuclides currently applicable in clinics and how to address the existing issues and problems based on our knowledge. [ABSTRACT FROM AUTHOR]

Background Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[18F]fluoro- D- glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64Cu]Cu-DOTATATE ([64Cu]Cu-[1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate). Case summary An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis. Discussion In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake. [ABSTRACT FROM AUTHOR]

Labeling and tracking existing and emerging cell-based immunotherapies using nuclear imaging is widely used to guide the preclinical phases of development and testing of existing and new emerging off-the-shelf cell-based immunotherapies. In fact, advancing our knowledge about their mechanism of action and limitations could provide preclinical support and justification for moving towards clinical experimentation of newly generated products and expedite their approval by the Food and Drug Administration (FDA). Here we provide the reader with a ready to use protocol describing the labeling methodologies and practical procedures to render different candidate cell therapies in vivo traceable by nuclear-based imaging. The protocol includes sufficient practical details to aid researchers at all career stages and from different fields in familiarizing with the described concepts and incorporating them into their work. [ABSTRACT FROM AUTHOR]

Endocarditis, a serious infectious disease, remains a diagnostic challenge in contemporary clinical practice. The advent of advanced imaging modalities has contributed significantly to the improved understanding and management of this complex disease. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has shown remarkable potential in improving the diagnostic accuracy of endocarditis. In the update of the Modified Duke Criteria, in 2023, The International Society for Cardiovascular Infectious Diseases (ISCVID) Working Group recognized specific 18F-FDG PET/CT findings as a major diagnostic criterion, particularly in patient with prosthetic valve endocarditis. The ability of PET to visualize metabolic activity allows for the identification of infective foci and could differentiate between infective and non-infective processes. This review examines the clinical utility of PET in differentiating infective endocarditis from other cardiovascular pathologies, highlighting its sensitivity and specificity in detecting native and prosthetic valve infections, including patients with transcatheter aortic valve implantation (TAVI), cardiac implantable devices (CIEDs), and left ventricular assistance devices (LVAD). Also, practical aspects and indications are illustrated to optimize the quality of imaging and reduce potential false positive results. In conclusion, the current use of PET in endocarditis has become a valuable diagnostic tool; as technological advances continue, PET will play an increasingly important role in the multidisciplinary approach to the management of endocarditis. [ABSTRACT FROM AUTHOR]

Bradykinin B1 receptor (B1R) has garnered attention as a cancer therapeutic and diagnostic target. Several reports on radiolabelled derivatives of B1R antagonists have shown favourable properties as imaging agents in cells highly expressing hB1R following transfection. In the present study, we assessed whether radiolabelled probes can detect B1R endogenously expressed in cancer cells. To this end, we evaluated 111In-labelled derivatives of a B1R antagonist ([111In]In-DOTA-Ahx-R954) using glioblastoma cell lines (U87MG and U251MG) with different B1R expression levels. Cellular uptake studies showed that the specific accumulation of [111In]In-DOTA-Ahx-R954 in U87MG was higher than that in U251MG, which correlated with B1R expression levels. Tissue distribution in U87MG-bearing mice revealed approximately 2-fold higher radioactivity in tumours than in the muscle in the contralateral leg. The specific accumulation of [111In]In-DOTA-Ahx-R954 in the tumour was demonstrated by the reduction in the tumour-to-plasma ratios in nonlabelled R954-treated mice. Moreover, ex vivo autoradiographic images revealed that the intratumoural distribution of [111In]In-DOTA-Ahx-R954 correlated with the localisation of B1R-expressing glioblastoma cells. In conclusion, we demonstrated that [111In]In-DOTA-Ahx-R954 radioactivity correlated with B1R expression in glioblastoma cells, indicating that radiolabelled derivatives of the B1R antagonist could serve as promising tools for elucidating the involvement of B1R in cancer. [ABSTRACT FROM AUTHOR]

Purpose of Review: There has been increasing use of multimodality imaging in the evaluation of cardiomyopathies. Recent Findings: Echocardiography, cardiac magnetic resonance (CMR), cardiac nuclear imaging, and cardiac computed tomography (CCT) play an important role in the diagnosis, risk stratification, and management of patients with cardiomyopathies. Summary: Echocardiography is essential in the initial assessment of suspected cardiomyopathy, but a multimodality approach can improve diagnostics and management. CMR allows for accurate measurement of volumes and function, and can easily detect unique pathologic structures. In addition, contrast imaging and parametric mapping enable the characterization of tissue features such as scar, edema, infiltration, and deposition. In non-ischemic cardiomyopathies, metabolic and molecular nuclear imaging is used to diagnose rare but life-threatening conditions such amyloidosis and sarcoidosis. There is an expanding use of CCT for planning electrophysiology procedures such as cardioversion, ablations, and device placement. Furthermore, CCT can evaluate for complications associated with advanced heart failure therapies such as cardiac transplant and mechanical support devices. Innovations in multimodality cardiac imaging should lead to increased volumes and better outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aims to investigate the role of nuclear imaging techniques in detecting incidentalomas and their impact on patient management. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted from February to May 2022. Studies in English involving patients undergoing nuclear medicine studies with incidental tumor findings were included. Data on imaging modalities, incidentaloma characteristics, management changes, and follow-up were extracted and analyzed. Results: Ninety-two studies involving 64.884 patients were included. Incidentalomas were detected in 611 cases (0.9%), with thyroid being the most common site. PET/CT with FDG and choline tracers showed the highest incidentaloma detection rates. Detection of incidentalomas led to a change in therapeutic strategy in 59% of cases. Various radiotracers demonstrated high sensitivity for incidentaloma detection, particularly in neuroendocrine tumors and prostate cancer. Conclusion: Nuclear imaging techniques play a crucial role in detecting incidentalomas, leading to significant changes in patient management. The high sensitivity of these modalities highlights their potential in routine oncology follow-up protocols. Future directions may include enhancing spatial resolution and promoting theranostic approaches for improved patient care. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to highlight presentations, acute findings and imaging phenotypes of patients presenting to the emergency department (ED) within 30 days of a transcatheter aortic valve replacement (TAVR). Methods: A retrospective review of patients diagnosed with aortic valve disease who underwent a TAVR between Jan 2015 and Nov 2021 at a large academic medical center was completed. From an initial 1271 patients, 146 were included based on their presentation to the ED within 30 days post-TAVR procedure. Patient data, including ED presentation details and imaging results, were recorded and de-identified. Results: Of the 146 post-TAVR patients, there were 168 ED visits within 30 days. The median time to ED after TAVR was 12 days. Respiratory symptoms were the most common complaint (27%). Neurological (23%) and cardiovascular symptoms (18%) followed. Cross-sectional imaging was conducted 250 times across visits, with an average of 1.7 scans per patient. CTs were most frequently used, followed by ultrasounds, especially echocardiograms and duplex extremity vasculature ultrasounds. 30.1% of patients had acute findings from imaging. Specific findings included heart failure (5.5%), access site complications (5.5%), pneumonia (5.5%), intracranial pathologies (3.4% for strokes and 0.7% for hematoma), and pleural effusion (3.4%). Echocardiograms and CTA chest were most associated with significant acute findings. Conclusion: Our study highlights the vital role of early and accurate imaging in post-TAVR patients within 30 days post-procedure. As transcatheter approaches rise in popularity, emergency radiologists become instrumental in diagnosing common post-procedural presentations. Continued research is essential to devise post-discharge strategies to curtail readmissions and related costs. Proper imaging ensures prompt, effective care, enhancing overall patient outcomes. [ABSTRACT FROM AUTHOR]

Leaves of soursop (Annona muricata) is a potential anti-cancer agent. However, there is no report on the effect of soursop leaf phytochemicals against osteosarcoma, a musculoskeletal cancer commonly affecting children and adults. The current study identified 28 metabolites from ethyl acetate leaf (EAL) extract through GC–MS chemoprofiling and subjected to in silico analysis against the potential protein target, platelet-derived growth factor receptor α (PDGFRA) of osteosarcoma, including absorption, distribution, metabolism, and excretion and toxicity (ADMET) analysis to identify the possible hit compounds. This resulted in three hit leaf bioactives, namely 2'-hydroxy-5'-methyl chalcone, linoleic acid and annonacin showing good binding affinity with a docking score of − 7.4, − 7.0 and − 6.9 kcal/mol, respectively. With ADMET analysis, 2'-hydroxy-5'-methyl chalcone and linoleic acid obeyed Lipinski's rule of five, whereas annonacin showed a slight violation. Among the three docked complexes, annonacin shows good stability during molecular dynamic simulation performed with PDGFRA. The concentration of the key marker compound, annonacin in EAL concentrate is found to be 5.032 ± 0.13 mg/g of leaf sample and is used for cytotoxicity assessment. Further, EAL concentrate exhibits cytotoxicity (IC50 value) on MG-63 osteosarcoma cells in vitro for concentrations ranging from 10 to 25 µg/mL. Nuclear imaging of osteoblast cells treated with EAL concentrate at 25 µg/mL concentration shows typical symptoms of apoptosis. In vitro cytotoxicity along with nuclear imaging confirmed EAL concentrate from soursop to be a potential drug candidate in developing new anti-cancer agent against osteosarcoma. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is characterized by abnormal growth of the myocardium with myofilament disarray and myocardial hyper-contractility, leading to left ventricular hypertrophy and fibrosis. Where culprit genes are identified, they typically relate to cardiomyocyte sarcomere structure and function. Multi-modality imaging plays a crucial role in the diagnosis, monitoring, and risk stratification of HCM, as well as in screening those at risk. Following the recent publication of the first European Society of Cardiology (ESC) cardiomyopathy guidelines, we build on previous reviews and explore the roles of electrocardiography, echocardiography, cardiac magnetic resonance (CMR), cardiac computed tomography (CT), and nuclear imaging. We examine each modality's strengths along with their limitations in turn, and discuss how they can be used in isolation, or in combination, to facilitate a personalized approach to patient care, as well as providing key information and robust safety and efficacy evidence within new areas of research. [ABSTRACT FROM AUTHOR]

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient's echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment. [ABSTRACT FROM AUTHOR]

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of heart failure in elderly patients. In this study, our primary objective was to explore the diverse applications and temporal significance of 1-h and 3-h imaging using 99mTc-PYP in the context of ATTR-CM. Additionally, we compared tracer kinetics in the heart and bone to comprehensively assess the diagnostic advantages and time-related considerations associated with these two incubation periods. Methods: Twenty-seven patients at Nagasaki University Hospital who underwent 99mTc-PYP planar, and SPECT cardiac imaging were classified into two groups (ATTR-CM-positive and -negative groups) based on the American Heart Association statement. Cardiac retention was assessed with both a semiquantitative visual score and a quantitative analysis. To assess bone accumulation, a ROI with an equal volume was drawn on the sternum and calculated as the bone-to-contralateral ratio (B/CL). We also evaluated correlation between heart-to-contralateral lung (H/CL) ratio and left ventricular wall thickness. Results: Among patients who underwent 99mTc-PYP imaging, the H/CL ratio was significantly higher at 1 h than at 3 h regardless of the group (from 2.20 ± 0.36 to 1.99 ± 0.35, p < 0.01 in the positive group and from 1.35 ± 0.12 to 1.19 ± 0.21, p = 0.01 in the negative group). The gap of H/CL between highest H/CL of negative case and lowest H/CL of positive case was narrower in 3 h. On the other hand, correlation between H/CL and left ventricular posterior wall thickness tends to be clearer in 3 h (p = 0.12, r = 0.30 for 1 h, p = 0.04, r = 0.39 at 3 h). Conclusion: Our study suggests that both 1-h and 3-h incubation times for 99mTc-PYP imaging have different benefits for ATTR cardiac amyloidosis. A one-hour incubation may be preferable for differential diagnostic purposes, while a three-hour incubation may provide greater utility in evaluating disease severity. [ABSTRACT FROM AUTHOR]

I-123 is preferential over I-131 for diagnostic SPECT imaging after a thyroidectomy to determine the presence and size of residual thyroid tissue for radioiodine ablation. Scattering degrades the quality of I-123 SPECT images, primarily due to the penetration of high-energy photons into the main photopeak. The objective of this study was to quantitatively and qualitatively investigate the impact of two widely used window-based scatter correction techniques, the dual energy window (DEW) and triple energy window (TEW) techniques, in I-123 postsurgical SPECT/CT thyroid imaging using an anthropomorphic phantom with small sizes of remnants and anatomically correct surrounding structures. For this purpose, non-scatter-corrected, DEW and TEW scatter-corrected SPECT/CT acquisitions were performed for 0.5–10 mL remnants within a phantom, with 0.5–12.6 MBq administered activities within the remnants, and without and with background-to-remnant activity ratios of 5% and 10%. The decrease in photons, the noise and non-uniformity in the background region due to scatter correction were measured, as well as the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) from small remnants. The images were also visually evaluated by two experienced nuclear medicine physicians. Scatter correction decreased photons to a higher extent in larger regions than smaller regions. Larger remnants yielded higher SNR and CNR values, particularly at lower background activities. It was found from the quantitative analysis and the qualitative evaluation that TEW scatter correction performed better than DEW scatter correction, particularly at higher background activities, while no significant differences were reported at lower background activities. Scatter correction should be applied in I-123 postsurgical SPECT/CT imaging to improve the image contrast and detectability of small remnants within the background. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses the results of the COLD-MI trial, which aimed to explore the impact of colchicine on myocardial denervation in patients who had experienced an acute myocardial infarction (AMI). The study found that colchicine reduced myocardial denervation in both the infarcted and non-infarcted zones of the heart. However, there were no significant effects on other parameters such as necrosis size or left ventricular ejection fraction. The study also noted an increase in gastrointestinal side effects with colchicine use. Overall, the findings suggest that colchicine may have a positive effect on reducing cardiac denervation in patients after AMI. [Extracted from the article]

Iron oxide nanoparticles (IONP) have been hailed as potential game-changers in biomedical imaging owing to their biocompatibility and size-dependent properties. One area where IONP has shown particular promise is magnetic resonance imaging (MRI), which traditionally uses superparamagnetic nanomaterials to produce negative contrast that darkens the tissues where nanoparticles accumulates. Unfortunately, this hypointense signal is a major drawback for clinical applications because it can make it difficult to identify the accumulated probes. As a result, researchers are exploring alternative options that can incorporate the advantages of IONP while also possessing valuable properties for molecular imaging. To achieve this goal, the most effective method involves not only utilizing positive contrast in MRI applications but also combining IONP with the unparalleled sensitivity of nuclear imaging techniques, for example, using radioisotopes to create PET/(T1)-MRI multimodal probes. To create such probes, various factors must be considered, including the radiolabeling strategy employed and overall complexity of the final nanoprobe. These nanoradiomaterials offer novel possibilities that span beyond the molecular imaging field, showing potential for the development of radiopharmaceuticals and theranostics. [ABSTRACT FROM AUTHOR]

Background: Silent or unrecognized myocardial infarction (UMI) diagnosed by surveillance electrocardiography (ECG) carries similarly poor prognosis as recognized MI (RMI) for poorly understood reasons. Methods: This study included 5430 consecutive patients who presented to the nuclear laboratory and underwent 2‐day stress and rest Tc‐99m sestamibi and ECG studies between March 1991 and June 1999. UMI was diagnosed if ECG showed Q‐wave MI in the absence of a history of RMI. We measured infarct size (% defect size as compared with the entire left ventricular sestamibi uptake), ejection fraction (EF, %), and summed difference score (SDS, sestamibi uptake by myocardium in stress minus sestamibi uptake in rest images as a marker of ischemia). Survival was determined by follow‐up survey (median 6 years). Results: We identified 346 UMIs, 628 RMIs, and 4456 subjects without MI (No MI). As compared with RMI, UMI patients had lesser abnormalities on nuclear scans (p <.0001 for all), including smaller infarct size (5.7% vs. 12.2%), higher EF (58% vs. 53%), and lesser ischemia (SDS; 3.9% vs. 2.7%). UMI prognosis was as poor as that of RMI (annual mortality rate 4.7% vs. 4.8% with No MI rate of 2.9%; p <.001 for all comparisons), and this persisted after multivariate analysis. Infarct size quantification successfully risk‐stratified ECG‐UMI patients, but UMI patients continued to predict mortality even if the infarct size was 0%. Conclusions: Although UMI patients have lesser abnormalities on nuclear scans, ECG‐based UMI continues to independently predict mortality, indicating the continuing relevance of ECG in clinical practice. [ABSTRACT FROM AUTHOR]

Overall, the incidence of osteoarticular infection among patients with IE is 6-8%, including bones, joints, and vertebral discs.[5],[145],[247],[516] The prevalence of spondylodiscitis ranges from 2% to 10% in patients with IE, including symptomatic and asymptomatic cases,[248],[517] while series of spontaneous spondylodiscitis have reported co-existing IE in up to 20-30% of patients.[[518], [520]] In general, the rate of IE is 10 times higher in patients with known spondylodiscitis. Patients with neutropaenia Neutropaenia is common in patients with haematological malignancies and in patients receiving chemotherapy for other malignancies, but is rare in patients presenting with IE.[814] Neutrophils play an important role in the pathogenesis of IE by producing layers of extracellular traps that entrap bacteria-platelet aggregates, leading to expansion of these aggregates, vegetation growth, and the destruction of tissues.[814] The diagnosis of IE can therefore be challenging in patients with neutropaenia, delaying the appropriate treatment, and worsening outcomes. Patient-centred care encourages involvement and collaboration between patients, families, and healthcare providers during all stages of diagnosis, treatment, and recovery.[[828], [830]] Core elements of patient-centred care include: involvement of family and caregivers, respect for patients' preferences and values, care co-ordination and continuity, information and education, as well as physical comfort and emotional support ( I Figure 14 i ).[[828], [830]] Graph: Figure 14 Concept of patient-centred care in infective endocarditis. [Extracted from the article]

Introduction: T cell Ig and ITIM domain receptor (TIGIT) is a next-generation immune checkpoint predominantly expressed on activated T cells and NK cells, exhibiting an unfavorable prognostic association with various malignancies. Despite the emergence of multiple TIGIT-blocking agents entering clinical trials, only a fraction of patients responded positively to anti-TIGIT therapy. Consequently, an urgent demand arises for noninvasive techniques to quantify and monitor TIGIT expression, facilitating patient stratification and enhancing therapeutic outcomes. Small antigen binding moieties such as nanobodies, are promising candidates for such tracer development. Methods: We generated a panel of anti-human or anti-mouse TIGIT nanobodies from immunized llamas. In addition, we designed a single-chain variable fragment derived from the clinically tested monoclonal antibody Vibostolimab targeting TIGIT, and assessed its performance alongside the nanobodies. In vitro characterization studies were performed, including binding ability and affinity to cell expressed or recombinant TIGIT. After Technetium-99m labeling, the nanobodies and the singlechain variable fragment were evaluated in vivo for their ability to detect TIGIT expression using SPECT/CT imaging, followed by ex vivo biodistribution analysis. Results: Nine nanobodies were selected for binding to recombinant and cell expressed TIGIT with low sub-nanomolar affinities and are thermostable. A sixfold higher uptake in TIGIT-overexpressing tumor was demonstrated one hour post- injection with Technetium-99m labeled nanobodies compared to an irrelevant control nanobody. Though the single-chain variable fragment exhibited superior binding to TIGIT-expressing peripheral blood mononuclear cells in vitro, its in vivo behavior yielded lower tumor-to-background ratios at one hour post- injection, indicating that nanobodies are better suited for in vivo imaging than the single-chain variable fragment. Despite the good affinity, high specificity and on-target uptake in mice in this setting, imaging of TIGIT expression on tumor- infiltrating lymphocytes within MC38 tumors remained elusive. This is likely due to the low expression levels of TIGIT in this model. Discussion: The excellent affinity, high specificity and rapid on-target uptake in mice bearing TIGIT- overexpressing tumors showed the promising diagnostic potential of nanobodies to noninvasively image high TIGIT expression within the tumor. These findings hold promise for clinical translation to aid patient selection and improve therapy response. [ABSTRACT FROM AUTHOR]

Background: This review focuses on multimodality imaging of cardiotoxicity in cancer patients, with the aim of evaluating the effectiveness of different techniques in detecting and monitoring cardiac changes associated with cancer therapy. Methods: Eight studies were included in the review, covering various imaging modalities such as cardiac magnetic resonance imaging, echocardiography, and multigated acquisition scanning. Results: Cardiac magnetic resonance imaging emerged as the most definitive modality, offering real-time detection, comprehensive assessment of cardiac function, the ability to detect early myocardial changes, and superior detection of cardiotoxicity when compared to the other imaging modalities. The studies also emphasize the importance of parameters such as left ventricular ejection fraction and global longitudinal strain in assessing cardiac function and predicting cardiotoxicity. Conclusion: Due to the common use of HER2 agents and anthracyclines within the breast cancer population, the LVEF as a critical prognostic measurement for assessing heart health and estimating the severity of left-sided cardiac malfunction is a commonly used endpoint. CTRCD rates differed between imaging modalities, with cardiac MRI the most sensitive. The use of multimodal cardiac imaging remains a nuanced area, influenced by local availability, the clinical question at hand, body habits, and medical comorbidities. All of the imaging modalities listed have a role to play in current care; however, focus should be given to increasing the provision of cardiac MRI for breast cancer patients in the future to optimize the detection of CTRCD and patient outcomes thereafter. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) traditionally has been characterized as a form of heart failure without therapeutic options, in particular with a lack of response to the established therapies of heart failure with reduced ejection fraction (HFrEF). However, this is no longer true. Besides physical exercise, risk factor modification, aldosterone blocking agents, and sodium-glucose cotransporter 2 inhibitors, specific therapies are emerging for specific HFpEF etiologies, such as hypertrophic cardiomyopathy or cardiac amyloidosis. This development justifies increased efforts to arrive at specific diagnoses within the umbrella of HFpEF. Cardiac imaging plays by far the largest role in this effort and is discussed in the following review. [ABSTRACT FROM AUTHOR]

Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions. [ABSTRACT FROM AUTHOR]

Introduction: The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post‐prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate‐specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate‐specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. Methods: At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re‐staged using PSMA PET imaging. We identified patients with PET‐avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. Results: Ninety‐four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local‐only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy‐three (77.7%) patients had a component of node failure, with 56 (59.6%) having node‐only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. Conclusion: The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition. [ABSTRACT FROM AUTHOR]

Artificial Intelligence for digital REStoration of Cultural Heritage (AIRES-CH) is a project focused on a creation of a cloud-native web application for the digital restoration of pictorial artworks through computer vision technologies applied to nuclear imaging raw data. In a previous work,it was shown that the task of associating an RGB colour image to a X-ray fluorescence (XRF) imaging raw data is feasible by means of a multidimensional neural network, and it was performed hyperparameter optimisation of the models. In this contribution we describe how the trained neural network is employed in the cloud-native web application for XRF raw data real time analysis. The RESTful API offering the Neural Network(s) has been developed using three frameworks and two languages, and a benchmark of its performances has been conducted. In the end, we comment the different outcomes of the benchmarking for the two different neural network branches. In the end, we comment the different outcomes of the benchmarking for the two different neural network branches. [ABSTRACT FROM AUTHOR]

Advances in cancer therapies have led to a global improvement in patient survival rates. Nevertheless, the price to pay is a concomitant increase in cardiovascular (CV) morbidity and mortality in this population. Increased inflammation and disturbances of the immune system are shared by both cancer and CV diseases. Immunological effects of anti-cancer treatments occur with both conventional chemotherapy and, to a greater extent, with novel biological therapies such as immunotherapy. For these reasons, there is growing interest in the immune system and its potential role at the molecular level in determining cardiotoxicity. Early recognition of these detrimental effects could help in identifying patients at risk and improve their oncological management. Non-invasive imaging already plays a key role in evaluating baseline CV risk and in detecting even subclinical cardiac dysfunction during surveillance. The aim of this review is to highlight the role of advanced cardiovascular imaging techniques in the detection and management of cardiovascular complications related to cancer treatment. [ABSTRACT FROM AUTHOR]

Cardiac implantable electronic device infection (CIED) is a rare complication, ranging from 0.5-1% in the first 6-12 months after device implantation. In the absence of a standardized protocol, the diagnosis of CIED infection is difficult due to a nonspecific clinical presentation. In some cases, the inflammatory process can mimicking as another cardiovascular disorder, including acute myocardial infarction. Today, the diagnosis of infection is based on the Duke criteria, including clinical, microbiological and echocardiographic data. However, the diagnostic accuracy of the criteria for device-related infective endocarditis is significantly reduced. Presented clinical case highlights the importance of increased vigilance in patients who have undergone device implantation and, in particular device replacement, and the usefulness of nuclear imaging techniques in asymptomatic patients or patients with an atypical clinical picture. [ABSTRACT FROM AUTHOR]

Introduction: The Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology Genitourinary Group (FROGG) guidelines and online EviQ protocols incorporate prostate‐specific membrane antigen (PSMA) positron emission tomography (PET)‐guided dose‐escalated intensity‐modulated radiation therapy (DE‐IMRT) for newly diagnosed lymph node (LN) positive prostate cancer. We evaluated late toxicity and efficacy outcomes following the FROGG and EviQ approach. Methods: Patients with LN‐positive‐only metastases on PSMA‐PET imaging were offered curative therapy with 3 months neoadjuvant androgen deprivation therapy (ADT) followed by DE‐IMRT and 3 years adjuvant ADT. IMRT was delivered via volumetric arc therapy (VMAT). We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET‐positive LNs, and 60 Gy in 45 Fx to elective pelvic nodes, contoured using the PIVOTAL guidelines. Results: Forty‐five patients were included. The median number of PET‐positive nodes boosted was 2 (range 1–6) and median boost volume 1.16 cc (range 0.15–4.14). Seventeen (38%) patients had PET‐positive nodes outside of PIVOTAL contouring guidelines. With 60 months median follow‐up, disease‐free, metastasis‐free, prostate cancer‐specific and overall survival were 88.1%, 95.3%, 100% and 91.5%. There were no in‐field nodal failures. Late grade 1, 2 and 3 gastrointestinal toxicities occurred in 4%, 2% and 0% of patients, and genitourinary toxicity in 18%, 18% and 4%. Lower limb grade 2 lymphoedema occurred in three patients (7%). Conclusion: Outcomes following FROGG guidelines and EviQ are promising, with high long‐term disease control and low toxicity. Contouring guidelines require modification due to the high rate of PET‐positive nodes demonstrated beyond recommended coverage. [ABSTRACT FROM AUTHOR]

Immunotherapy has become a mainstay of cancer therapy. Since chimeric antigen receptor (CAR) T immunotherapy achieves unprecedented success in curing hematological malignancies, the possibility of it revolutionizing the paradigm of solid tumors has aroused increasing attention. However, the restricted accessibility to tumor parenchyma, the immunosuppressive tumor microenvironment, and antigen heterogeneity of solid tumors make it difficult to replicate its success. Therefore, dynamic evaluation of CAR T cells' tumor accessibility, intratumoral viability, and anti‐tumor cytotoxicity is necessary to facilitate its translation to solid tumors. Besides, real‐timely imaging above events in vivo can help evaluate therapeutic responses and optimize CAR T immunotherapy for solid tumors. Nuclear imaging, including positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) imaging, is frequently applied for evaluating adoptive cell therapies owing to its excellent sensitivity, high tissue penetration, and great translation potential. In addition, quantitative analysis can be performed in dynamic and noninvasive patterns. This review focuses on recent advances in PET/SPECT technologies and imaging probes in monitoring CAR T cells' migration, viability, and cytotoxicity to solid tumors post‐administration. Prospects of what should be done in the next stage to promote CAR T therapy's application in solid tumors are also discussed. [ABSTRACT FROM AUTHOR]

Post-surgical I-123 and I-131 SPECT/CT imaging can provide information on the presence and sizes of thyroid remnants and/or metastasis for an accurate re-staging of disease to apply an individualized radioiodine therapy. The purpose of this study was to develop and validate a neck–thyroid phantom with small sizes of thyroid remnants to be utilized for the optimization of post-surgical SPECT/CT imaging. 3D printing and molding techniques were used to develop the hollow human-shaped and -sized phantom which enclosed the trachea, esophagus, cervical spine, clavicle, and multiple detachable sections with different sizes of thyroid remnant in clinically relevant positions. CT images were acquired to evaluate the morphology of the phantom and the sizes of remnants. Triple-energy window scattered and attenuation corrected SPECT images were acquired for this phantom and for a modified RS-542 commercial solid neck–thyroid phantom. The response and sensitivity of the SPECT modality for different administered I-123 and I-131 activities within the equal-size remnants of both phantoms were calculated. When we compared the phantoms, using the same radiopharmaceutical and similar activities, we found that the measured sensitivities were comparable. In all cases, the I-123 counting rate was higher than the I-131 one. This phantom with capabilities to insert different small sizes of remnants and simulate different background-to-remnants activity ratios can be utilized to evaluate postsurgical thyroid SPECT/CT imaging procedures. [ABSTRACT FROM AUTHOR]

Background: The assessment of anomalous coronary arteries (AAOCA) remains controversial without an optimal stress modality for ischemia. We evaluated the value of PET-CT myocardial perfusion imaging in these patients and subsequent management. Methods and results: AAOCA patients (n = 82) undergoing PET-CT from 2015 to 2021 were retrospectively chart reviewed. Multivariable analyses performed to assess relevant clinical and imaging factors associated with ischemia on PET and AAOCA surgery. Key characteristics include mean age 45 ± 20 years, 30 (37%) female, 45 (55%) with chest pain, 19 (23%) anomalous left main coronary artery, 58 (71%) anomalous right coronary artery, 26 (32%) with objective ischemia on PET-CT, and 37 (45%) who underwent AAOCA surgery. Adverse outcomes over mean follow-up of 2.2 ± 1.8 years included one death and two myocardial infarctions. Anomalous left main was independently associated with ischemia on PET-CT, odds ratio (95% confidence intervals) 4.15 (1.31–13.1), P =.006. Chest pain and ischemia on PET-CT were independently associated with and provided incremental prognostic value for surgery, odds ratio 9.73 (2.78–34.0), P <.001 and 6.79 (1.99–23.2), P =.002, respectively. Conclusion: Ischemia on PET-CT occurred in a third of our cohort, identifying patients who may benefit from surgery. Larger studies are needed to evaluate the interplay between AAOCA, ischemia by PET and surgery. [ABSTRACT FROM AUTHOR]

The expression status of human epidermal growth factor receptor 2 (HER2) in cancer predicts response to HER2-targeted therapy. Therefore, its accurate determination is of utmost importance. In recent years, there has been an increase in research on noninvasive techniques for molecular imaging, as this method offers the advantages of a more accurate determination of HER2 status without the need for multiple biopsies. The technetium-labeled single-domain antibody RAD201, previously known as 99mTc-NM-02, has been shown to be safe for use in breast cancer imaging with reasonable radiation doses, favorable biodistribution, and imaging characteristics. Methods: A total of six HER2-positive, heavily pretreated patients with different cancer types aged between 42 and 69 years (5 women and 1 man; the median age of 55.5) have been examined. In six of seven scans, the patients were administered 500 ml of Gelofusine® solution (40 mg/ml) for radiation protection before the tracer injection (434 ± 42 MBq). Planar scans were acquired with the patient supine at 10 min, 60 min, 160 min, 20 h, and 24 h after injection. A CT scan was acquired at 95 min, followed by local tomographic SPECT imaging. Results: One patient was scanned twice with RAD201, 3 months apart, resulting in a total of seven scans for six patients. Here, we show that the use of RAD201 in our patient group shows the same favorable biodistribution as in a previous study with RAD201 (NCT04040686) and that the radiation dose to the critical organ kidney can be reduced by the application of the plasma expander Gelofusine® by almost 50%. Conclusion: RAD201 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic (breast) cancer, regardless of ongoing HER2-targeted antibody treatment. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) remains to be a heterogeneous disease with high morbidity and mortality rates, which can affect native valves, prosthetic valves, and intra-cardiac devices, in addition to causing systemic complications. The combination of clinical, laboratory, and cardiac imaging evaluation is critical for early diagnosis and risk stratification of IE. This can facilitate timely medical and surgical management to improve patient outcomes. Key imaging findings for IE include vegetations, valve perforation, prosthetic valve dehiscence, pseudoaneurysms, abscesses, and fistulae. Transthoracic echocardiography continues to be the first-line imaging modality of choice, while transesophageal echocardiography subsequently provides an improved structural assessment and characterization of lesions to facilitate management decision in IE. Recent advances in other imaging modalities, especially cardiac computed tomography and 18F-fluorodeox-yglucose positron emission tomography, and to a lesser extent cardiac magnetic resonance imaging and other nuclear imaging techniques, have demonstrated important roles in providing complementary IE diagnostic and prognostic information. This review aims to discuss the individual and integrated utilities of contemporary multi-modality cardiac imaging for the assessment and treatment guidance of IE. [ABSTRACT FROM AUTHOR]

The concept of personalized medicine refers to the tailoring of medical treatment to each patient's unique characteristics. Scientific advancements have led to a better understanding of how a person's unique molecular and genetic profile makes them susceptible to certain diseases. It provides individualized medical treatments that will be safe and effective for each patient. Molecular imaging modalities play an essential role in this aspect. They are used widely in screening, detection and diagnosis, treatment, assessing disease heterogeneity and progression planning, molecular characteristics, and long-term follow-up. In contrast to conventional imaging approaches, molecular imaging techniques approach images as the knowledge that can be processed, allowing for the collection of relevant knowledge in addition to the evaluation of enormous patient groups. This review presents the fundamental role of molecular imaging modalities in personalized medicine. [ABSTRACT FROM AUTHOR]

Nuclear imaging is a highly sensitive and noninvasive imaging technique that has become essential for medical diagnosis. The use of radiolabeled nanomaterials capable of acting as imaging probes has shown rapid development in recent years as a powerful, highly sensitive, and noninvasive tool. In addition, quantitative single-photon emission computed tomography (SPECT) images performed by incorporating radioisotopes into nanoparticles (NPs) might improve the evaluation and the validation of potential clinical treatments. In this work, we present a direct method for [99mTc]Tc-radiolabeling of FITC-tagged silk fibroin nanoparticles (SFN). NPs were characterized by means of dynamic light scattering and scanning electron microscopy. In vitro studies were carried out, including the evaluation of stability in biological media and the evaluation of hemocompatibility and genotoxicity using the cytokinesis block micronucleus (CBMN) assay. The radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼95%) and high stability in biological media. Hydrodynamic properties of the radiolabeled NPs remain stable after dual labeling. The interaction of SFN with blood elicits a mild host response, as expected. Furthermore, CBMN assay did not show genotoxicity induced by [99mTc]Tc-FITC-SFN under the described conditions. In conclusion, a feasible and robust dual-labeling method has been developed whose applicability has been demonstrated in vitro, showing its value for further investigations of silk fibroin NPs biodistribution in vivo. [ABSTRACT FROM AUTHOR]

Myocardial perfusion single photon emission computed tomography (SPECT) is widely used in assessing coronary artery disease (CAD) owing to its proven efficacy in extensive clinical experience. Like other functional tests, myocardial SPECT is recommended for the diagnosis of obstructive CAD, risk stratification assessment, and treatment decision making. Besides quantifying left ventricular volume, global and regional function by electrocardiography (ECG)-gated acquisition, myocardial SPECT can identify myocardial ischemia, scars, stunning, and viable hibernating myocardium. It provides comprehensive functional data across the spectrum of CAD and a costeffective strategy in patients with intermediate pre-test probability of CAD or with a history of ischemic cardiomyopathy. With ongoing advances in cardiovascular prevention and risk factor management many patients referred for testing now have a low-to-intermediate probability of CAD. Besides, CAD has become a chronic condition resulting from novel therapeutic strategies. Against this background, approaches combining anatomical and functional tests in sequence or simultaneously include coronary artery calcium score integrated with perfusion imaging or fusion SPECT/coronary computed tomography angiography (CCTA). In this review we summarize current indications for myocardial perfusion SPECT and integration of SPECT with other imaging techniques to improve diagnostic performance, patient management, and outcome prediction in CAD. [ABSTRACT FROM AUTHOR]

Purpose: Accurate preoperative localization is imperative to facilitate a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). This study aims to compare the diagnostic value of standard-of-care localization techniques (ultrasound [US] and 99mTechnetium (99mTc) -sestamibi scintigraphy) to [F-18]-fluorocholine positron emission tomography/magnetic resonance imaging (FCH-PET/MRI) to determine the additional clinical usefulness of PET/MRI in a Canadian cohort. Methods: We conducted a prospective, appropriately powered, study to compare the diagnostic value of -FCH PET/MRI to that of the US and 99mTc-sestamibi scintigraphy for localization of parathyroid adenomas in a patient with pHPT. The primary outcome was the per-lesion sensitivity and positive predictive value (PPV) of FCH-PET/MRI, US, and 99mTc-sestamibi scintigraphy. Intraoperative surgeon localization, parathormone levels, and histopathological findings were used as reference standards. Results: Forty-one patients underwent FCH-PET/MRI of which 36 patients had parathyroidectomy. In these 36 patients, 41 parathyroid lesions were histologically confirmed as adenomas or hyperplastic glands. Per-lesion sensitivity of FCH-PET/MRI was 82.9% and of US and 99mTc-sestamibi scintigraphy combined at 50.0%, respectively. The sensitivity of FCH-PET/MRI was superior to that of US and 99mTc-sestamibi scintigraphy (p = 0.002). In the 19 patients in whom both US and 99mTc-sestamibi scintigraphy were negative, PET/MRI correctly identified the parathyroid adenoma in 13 patients (68%). Conclusions: FCH-PET/MRI is a highly accurate imaging modality for localization of parathyroid adenomas in a tertiary center in North America. It is a superior functional imaging modality to 99mTc-sestamibi scintigraphy alone and more sensitive for localization of parathyroid lesions than US and 99mTc-sestamibi scintigraphy combined. This imaging modality could become the most valuable preoperative localization study given its superior performance in localizing parathyroid adenomas. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR. [ABSTRACT FROM AUTHOR]

Adrenal neoplasms rarely occur in children. They can be diagnosed in the presence of endocrine, metabolic or neurological problems, an abdominal mass, more rarely an adrenal incidentaloma, or in the context of an adrenal mass discovered in the evaluation of childhood cancer including hematologic malignancy. According to standard medical practice, pediatric malignancies are almost always evaluated by 18F-fluorodeoxyglucose positron emission tomography with computed tomography ([18F]FDG PET/CT). Nuclear imaging using specific radiotracers is also an important tool for diagnosing and staging neuroblastoma, pheochromocytoma, hormone hypersecretion, or indeterminate adrenal masses. The Hippocratic oath "primum non nocere" encourages limitation of radiation in children per the ALARA concept (as low as reasonably achievable) but should not lead to the under-use of nuclear imaging because of the potential risk of inaccurate diagnosis or underestimation of the extent of disease. As in adults, nuclear imaging in children should be performed in conjunction with hormone evaluation and morphological imaging. [ABSTRACT FROM AUTHOR]

18F-FDG PET/CT is a valuable diagnostic tool in infective endocarditis (IE). However, the prognostic value is unclear. This study aims to evaluate the prognostic performance of 18F-FDG PET/CT in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). We retrospectively included 76 patients treated for definite IE (NVE and PVE) that underwent 18F-FDG PET/CT between January 2016 and December 2018. Clinical, echocardiographic and 18F-FDG PET/CT (pathologic valvular 18F-FDG uptake, extracardiac complications (ECC)) data were collected. The primary endpoint was defined as mortality or recurrence of IE at a one-year follow-up. Pathologic valvular 18F-FDG uptake was detected in 32 of 57 (56.1%) patients, 30% (9/30) in NVE and 85.2% (23/27) in PVE group. Atrial fibrillation (OR 3.90, 95% CI = 1.14–16.3), prior anticoagulation treatment (OR 6.37, 95% CI = 1.89–26.7), large vegetation (≥ 10 mm) (OR 4.05, 95% CI = 1.14–16.1), perivalvular complications (OR 7.22, 95% CI = 1.68–55.1) and abscess (OR 10.9, 95% CI = 1.84–283) were associated with positive PET/CT. Extracardiac complications were found in 27 of 76 (35.5%) patients, 42.9% (18/42) in the NVE and 26.5% (9/34) in the PVE group. Pathological valvular tracer uptake (HR 1.20, 95% CI = 0.43–3.37) or extracardiac complications (HR 0.58, 95% CI = 0.21–1.62) were not associated with the occurrence of the primary endpoint. Our study could not demonstrate a prognostic value of 18F-FDG PET/CT in IE, but confirms high diagnostic performance, which may compromise prognostic significance by accelerated optimal treatment because of earlier diagnostic certainty. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy or Takotsubo Syndrome (TTS) is a reversible left ventricular dysfunction syndrome that is increasingly being recognized. Recent advances in nuclear imaging have allowed us to study TTS in greater detail. We searched the PubMed and Medline databases and identified 53 publications with 221 patients reporting nuclear imaging findings in TTS. The age of the patients ranged from 17 to 87 years and were predominantly women (88.2%). The TTS variant was apical (typical) in 170 (76.9%), mid-ventricular in 23 (10.4%), and basal (reverse TTS) in 2 (0.9%). Cardiac perfusion was assessed using 99mTc sestamibi (MIBI) SPECT, 99mTc tetrofosmin SPECT, 201Tl SPECT, 82Rb PET, 201Tl SPECT, and 13N ammonia PET. Additional studies used were 123I MIBG SPECT, 123I BMIPP SPECT, 18F FDG PET, 67Ga citrate, and 11C hydroxy-ephedrine. A perfusion defect was seen in 69 (31.2%), and an inverse perfusion–metabolism mismatch (normal or near-normal perfusion with absent myocardial metabolic activity) was seen in 183 (82.8%) patients. Nuclear imaging has a significant role in evaluating, diagnosing, and prognosticating patients with TTS. As nuclear imaging technology evolves, we will surely gain more insights into this fascinating disorder. [ABSTRACT FROM AUTHOR]

Background: Quantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). Methods: Consecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. Results: Seventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. Conclusion: CPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is the most common endocrine malignancy in the world; however, these patients usually experience a high survival rate if they receive appropriate and timely treatment. Meanwhile, patients classified as having differentiated thyroid cancer with high thyroglobulin and negative iodine scan [Differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy (TENIS)] are always considered a diagnostic-therapeutic challenge. Materials and Methods: We conducted a comprehensive literature search of published papers in the PubMed/MEDLINE database regarding nuclear imaging in differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy. We included all human studies in this field. Results: In this review, we examined four major groups of imaging studies aimed at identifying GLUT, SSTR, PSMA and FAP receptors in patients with TENIS. The diagnostic rate of 2-[18F]FDG PET/CT in these patients has been reported as 63-81% based on various studies. Also, [68Ga]Ga-DOTATATE PET/CT, [68Ga]Ga-PSMA PET/CT and [68Ga]Ga-FAPI PET/CT scans have shown good results in these patients. Conclusion: [68Ga]Ga-FAPI PET/CT imaging has the highest diagnostic rate among these patients. Given the theranostic capability of FAPI and the numerous complications and limited inclusion criteria for treatment with tyrosine kinase inhibitors, it has been the next step in the treatment of patients with TENIS. Therefore, more extensive studies in this field are warranted. [ABSTRACT FROM AUTHOR]

Aims Diagnosis of prosthetic valve endocarditis (PVE) by positron emission computed tomography angiography (PET/CTA) is based on visual and quantitative morpho-metabolic features. However, the fluorodeoxyglucose (FDG) uptake pattern can be sometimes visually unclear and susceptible to subjectivity. This study aimed to validate a new parameter, the valve uptake index [VUI, maximum standardized uptake value (SUVmax)−mean standardized uptake value (SUVmean)/SUVmax], designed to provide a more objective indication of the distribution of metabolic activity. Secondly, to re-evaluate the utility of traditionally used PVE imaging criteria and determine the potential value of adding the VUI in the diagnostic algorithm of PVE. Methods and results Retrospective analysis of 122 patients (135 prosthetic valves) admitted for suspicion of endocarditis, with a conclusive diagnosis of definite (N = 57) or rejected (N = 65) PVE, and who had undergone a cardiac PET/CTA scan as part of the diagnostic evaluation. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern, and the presence of endocarditis-related anatomic lesions. The VUI, SUVmax, and SUVratio values were 0.54 ± 0.1 vs. 0.36 ± 0.08, 7.68 ± 3.07 vs. 3.72 ± 1.11, and 4.28 ± 1.93 vs. 2.16 ± 0.95 in the 'definite' PVE group vs. the 'rejected' group, respectively (mean ± SD; P < 0.001). A cut-off value of VUI > 0.45 showed a sensitivity, specificity, and diagnostic accuracy for PVE of 85%, 88%, and 86.7% and increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria. Conclusions The VUI demonstrated good diagnostic accuracy for PVE, even increasing the diagnostic power of the traditionally used morphometabolic parameters, which also confirmed their own diagnostic performance. More research is needed to assess whether the integration of the VUI into the PVE diagnostic algorithm may clarify doubtful cases and thus improve the diagnostic yield of PET/CTA. [ABSTRACT FROM AUTHOR]

Background and objectives: Myocardial perfusion imaging with cardiac single-photon emission tomography (SPECT) is widely available for the detection of coronary artery disease (CAD) with high diagnostic and prognostic accuracy for women. A large proportion of symptomatic women with true myocardial perfusion defects in SPECT referred to coronary angiography have an absence of CAD—a condition named INOCA (ischemia with nonobstructive CAD). Additionally, the INOCA endotypes are rarely correctly diagnosed, and therefore, no tailored therapy is prescribed. Materials and methods: The cardiac SPECT for women was performed from 2018 to 2021. Patients with perfusion defect were analyzed according to further prescribed diagnostic tests used to diagnose CAD. According to the diagnostic criteria, patients with INOCA were selected as candidates for invasive microvascular physiology measurements. The correlation was calculated between SPECT results and clinical characteristics, symptoms, and risk factors. Results: A total of 726 women with suspected CAD were analyzed. True myocardial perfusion defects were detected in 125 patients (17.2%). During coronary angiography in 70 (56.0%) women, atherosclerosis in epicardial arteries was not observed. In 17 (20.9%) patients, obstructive CAD was present. Correlation was found between perfusion defect in SPECT and cardiovascular risk factors, including overweight, obesity, arterial hypertension, and dyslipidemia. Women with typical angina were more likely to have INOCA, but with "noncardiac" symptoms—CAD. In total, 68 female patients met three inclusion criteria for INOCA and were selected as candidates for invasive diagnostic testing. Conclusions: The created registry proves the important role of cardiac SPECT and great need for the development of invasively detected physiological measurements. The combination of both interventions could significantly change the future directions for INOCA patients, improving treatment strategies and clinical outcomes, especially knowing the number of risk factors and varying clinical presentation. The study will be continued by performing invasive testing of coronary microvascular function to expand the competence about what is known about INOCA patients. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Because TNBC lacks the expression of commonly targeted receptors, it is challenging to develop a new imaging agent for this cancer subtype. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA–protein complexes that have been linked to tumor development and progression. Considering the high expression of hnRNPA2B1, an hnRNP subtype, in TNBC MDA-MB-231 cells, this study aimed to develop a novel hnRNPA2B1 antibody-based nuclear imaging agent. The hnRNPA2B1-specific antibody was radiolabeled with 64Cu and evaluated in vitro and in vivo. The trans-cyclooctene (TCO) was functionalized on the antibody to obtain hnRNP-PEG4-TCO and reactive tetrazine (Tz) on the ultrastable bifunctional chelator PCB-TE2A-alkyne to yield PCB-TE2A-Tz for the inverse electron demand Diels–Alder reaction. The 64Cu-radiolabeled antibody was administered and imaged at 1–18 h time points for conventional imaging. Alternatively, the unlabeled antibody conjugate was administered, and 48 h later radiolabeled 64Cu-PCB-TE2A-Tz was administered to the same mice for the pretargeting strategy and imaged at the same time intervals for direct comparison. The tumor was successfully visualized in both strategies, and comparatively, pretargeting showed superior results. The 64Cu-PCB-TE2A-Tz was successfully clicked at the tumor site with hnRNP-PEG4-TCO and the non-clicked were concurrently eliminated. This led to increase the tumor uptake with extremely high tumor-to-background ratio manifested by positron emission tomography (PET) imaging and biodistribution studies. [ABSTRACT FROM AUTHOR]

Aptamers are short oligonucleotides that bind to specific target molecules. They have been extensively explored in biomedical applications, including biosensing, medical imaging, and disease treatment. Their adjustable affinity for specific biomarkers stimulates more translational efforts, such as nuclear imaging of tumors in preclinical and clinical settings. In this review, we present recent advances of aptamer-based nuclear imaging and compare aptamer tracers with other biogenic probes in forms of peptides, nanobodies, monoclonal antibodies, and antibody fragments. Fundamental properties of aptamer-based radiotracers are highlighted and potential directions to improve aptamer's imaging performance are discussed. Despite many translational obstacles to overcome, we envision aptamers to be a versatile tool for cancer nuclear imaging in the near future. [ABSTRACT FROM AUTHOR]

Systemic juvenile idiopathic arthritis (sJIA, also called Still's disease) is a rare childhood auto‐inflammatory disease with significant morbidity. This case report illustrates the clinical course and highlights diagnostic challenges. FDG‐PET/CT imaging may be beneficial in the diagnostic process for some cases, in order to achieve rapid diagnosis and early treatment. [ABSTRACT FROM AUTHOR]