Current Radiopharmaceuticals - Volume 14, Issue 3, 2021

Positron-emission-tomography (PET) using the radiopharmaceutical ¹⁸F-fluorodeoxyglucose (FDG) has become an established and validated molecular imaging modality for characterization of the inflammatory activity of atherosclerotic plaque. In the latest years, new innovative radiopharmaceuticals and applications have emerged, providing specific information on atherosclerotic plaque biology, particularly focused on inflammatory processes. To review and highlight recent evidence on the role of PET for atherosclerosis imaging using emerging radiotracers. A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the usefulness of nuclear hybrid imaging in atherosclerosis imaging using ¹⁸F-- sodium fluoride PET, CXCR4-targeted PET, and amyloid-β-targeted PET. Atherosclerosis imaging with PET using emerging, specific tracers holds promise in improving our understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. There is increasing, high-quality evidence on the usefulness of ¹⁸F-sodium fluoride PET and – to a lesser extent – CXCR4-targeted PET, whereas amyloid-β-targeted PET is still in its infancy. F-sodium fluoride PET, CXCR4-targeted PET and amyloid-β-targeted PET may be used to obtain molecular information on different aspects of plaque biology. Further work is required to improve the technical aspects of these imaging techniques and to elucidate their ability to predict adverse cardiac events prospectively.

Acute myocardial infarction is one of the leading causes of death in the western world. Despite major improvements in myocardial reperfusion with sophisticated percutaneous coronary intervention technologies and new antithrombotic agents, there is still no effective therapy for preventing post- infarction myocardial injury and remodeling. Death of cardiomyocytes following ischemia results in “danger signals” that elicit an inflammatory reaction to remove cell debris and form scar tissue. Optimal healing of the damaged myocardial tissue requires a coordinated cellular response for sufficient wound healing and scar formation. However, if this inflammatory reaction is overactive or incompletely resolved, adverse left ventricular remodeling and heart failure may occur. Treatment aimed at the modulation of the post-MI inflammatory response has been widely pursued and investigated. Although improved infarct healing was shown in many experimental preclinical studies, to date, clinical trials using anti-inflammatory treatment strategies have been far less successful. Clearly, a need exists for predicting and selecting patients at risk and selecting the most appropriate therapy for individual patients. To this end, imaging of the post-MI response has been a topic of significant interest. In this review, we first discuss the clinical complications resulting from myocardial inflammation following AMI and the need for non-invasive imaging techniques using radiolabeled tracers. We then discuss the inflammatory reaction cascade following acute myocardial infarction, the inflammatory reaction cascade following acute myocardial infarction focusing on inflammatory cell types involved herein, and potential imaging targets for identifying these cells during the inflammatory process. In addition, we discuss specific characteristics and limitations of various preclinical animal models for ischemic heart disease since they are crucial in the development and evaluation of the imaging techniques. Finally, we discuss the need for non-invasive imaging approaches using radiolabeled tracers.

In medical imaging, Artificial Intelligence is described as the ability of a system to properly interpret and learn from external data, acquiring knowledge to achieve specific goals and tasks through flexible adaptation. The number of possible applications of Artificial Intelligence is also huge in clinical medicine and cardiovascular diseases. To describe for the first time in literature, the main results of articles about Artificial Intelligence potential for clinical applications in molecular imaging techniques, and to describe its advancements in cardiovascular diseases assessed with nuclear medicine imaging modalities. A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the most relevant articles that evaluated the technological insights of AI in nuclear cardiology applications. Artificial Intelligence may improve patient care in many different fields, from the semi-automatization of the medical work, through the technical aspect of image preparation, interpretation, the calculation of additional factors based on data obtained during scanning, to the prognostic prediction and risk-- group selection. Myocardial implementation of Artificial Intelligence algorithms in nuclear cardiology can improve and facilitate the diagnostic and predictive process, and global patient care. Building large databases containing clinical and image data is a first but essential step to create and train automated diagnostic/prognostic models able to help the clinicians to make unbiased and faster decisions for precision healthcare.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, pathologically characterized by non-caseating granulomas involving several organs and tissues. This pathological process can eventually affect the heart during his course leading to fibrosis associated with systolic dysfunction, conduction disturbance, and even sudden cardiac death. Due to this prognostic impact, diagnosis is crucial to optimize clinical management. The low sensitivity of endomyocardial biopsy and its invasive nature prevents its application as a first-line diagnostic approach. Thus, several efforts have been dedicated to the identification of advanced imaging tools for the diagnosis and monitoring of cardiac involvement in systemic sarcoidosis, including Positron Emission Tomography (PET). Starting from strengths and disadvantages of 18F-Fluorodeoxyglucose (18F-FDG) PET imaging, the present narrative review will summarize state of the art and future perspectives about radiotracers other than 18F-FDG of potential interest in the field of CS, including somatostatin receptor- ligands, proliferation markers and hypoxia displaying agents.

Cardiac amyloidosis is a progressive infiltrative disease for which new treatments are now available. As therapy should be started as early as possible to avoid complications such as restrictive cardiomyopathy, arrhythmias and heart failure, a prompt and reliable diagnosis by means of non-invasive tests would be highly warranted. Electrocardiography, echocardiography and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy, but none of these modalities can effectively differentiate the cardiac amyloid subtypes. We aim to highlight the most relevant findings in the literature of molecular imaging in the assessment of patients with cardiac amyloidosis and to underline future clinical perspective. We performed multiple searches using Pub-Med databases in order to find important original articles on the role of molecular imaging in the assessment of patients affected by CA. Several search terms were used, such as “cardiac amyloidosis”; “Light-chain amyloidosis”; “Transthyretin amyloid cardiomyopathy”; “bone scintigraphy”; “single photon emission tomography” or “SPECT”; “Positron emission tomography or PET”, and “cardiac imaging”. All radiopharmaceuticals tracing cardiac amyloidosis were also included. Several studies about the role of SPECT with bone-seeking tracer (47 articles) and innervation tracer (9 articles) in the work-up of CA, as well as new PET amyloid-binding (14 articles) and bone radiotracer (4 articles) have been reviewed and discussed. Molecular imaging represents a sensitive tool for early assessment of both amyloid burden and cardiac innervation, to differentiate between subtypes and to monitor disease burden, disease progression, and potential response to therapy.

Cardiac and vascular infection is an arising cause of mortality and morbidity in the adult population. Diagnosis based on culture and anatomic imaging are frequently inconclusive. Radiolabeled leucocyte scintigraphy plays a useful role in the diagnosis and management of these serious infectious conditions. In this paper, we present an update on the diagnostic performance of single- photon emission tomographic (SPECT) techniques using different radionuclides in the management of patients with cardiac and vascular infections. We performed a thorough search of recent literature on the topic. We present a discussion on the clinical utility of different SPECT tracers in cardiac and vascular infections, including infective endocarditis, cardiac implantable electronic device (CIED) infections, left ventricular assist device infection, and vascular graft infection. Radionuclide technique using SPECT tracers is a useful imaging modality in the diagnosis of cardiac infection. Among the different SPECT tracers for infection imaging, radiolabeled leucocyte scintigraphy is currently the most useful tool in the diagnosis and management of patients with suspected cardiac and vascular infection. Radiolabeled leucocyte scintigraphy has a high specificity, a result of the ability of the leucocytes to accumulate as sites of pyogenic infection but not at sites of sterile inflammation such as seen in the early post-operative period or in response to the presence of a prosthetic cardiac or vascular material. Limited experience with radiotracers for in vivo labelling of leucocytes such as ^99mTc-sulesomab and ^99mTc-besilesomab show acceptable diagnostic performance without the need for the tedious process of ex-vivo labeling. ⁶⁷Ga scintigraphy used to be popular for cardiac and vascular infection imaging. Its use has run out of favor following the availability of more effective molecular imaging methods. SPECT techniques with radiolabeled leucocyte scintigraphy has a high diagnostic performance in the evaluation of patients with suspected cardiac or vascular infection. It is able to confirm or reject the presence of infection when results of anatomic imaging or culture remain inconclusive. Its diagnostic performance is not compromised by sterile inflammation occurring in the early post-operative period or in response to implanted prosthetic materials.

Endocarditis, myocarditis and pericarditis are a heterogeneous group of phenotypic syndromes where the culprit area of inflammation is the heart. Inflammation may be determined by an infective agent, toxins, drugs or an activated immune system. Clinical manifestations can be subtle and diagnosis remains a challenge for cardiologists, requiring high level of suspicion and advanced multimodal cardiac imaging to avoid life-threatening consequences. The purpose of this review is to report the recent advances of PET/CT imaging with 18FDG in helping the management of patients affected by inflammatory heart disease. Two independent reviewers searched in PubMed articles published before or in June 2019 and final decisions on the inclusion of references were done in consensus with a third reviewer. At the end of the selection process 23/206 articles on “cardiac inflammation”; 26/235 articles on “endocarditis”, “prosthetic heart valve”, “pacemaker”, “implantable cardiac device”; 7/103 articles on “myocarditis”; 13/330 articles on sarcoidosis” and 2/19 articles on “pericarditis” were included. Compared with the conventional methods, molecular imaging has the advantage to non-invasively and directly trace the inflammatory process, and to identify earlier the presence and the extent of intra-cardiac and extra-cardiac involvement, to enable quantification of disease activity, guide therapeutic interventions, and monitor treatment success.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. AMI causes necrosis of cardiac cells and triggers a complex inflammatory response, affecting infarct size, cardiac function and clinical outcomes. This inflammatory response can be divided into 3 phases: 1) the pro-inflammatory phase, in which the release of damage-associated molecular patterns from necrotic cells triggers the secretion of pro-inflammatory mediators and attracts immune cells to clean the debris, further damaging viable myocardium, 2) the reparative phase, in which anti-inflammatory signals activate immune-modulating cells and trigger the production of a stable scar, 3) the maturation phase, in which inflammatory and fibrotic signals are suppressed, but may persist, leading to left ventricular adverse remodelling. Thus, the inflammatory response is an appealing therapeutic target to improve the outcomes of patients with AMI. Numerous anti-inflammatory therapies have shown potential in animal models, but the translation to human trials exhibited limited benefit. Glucocorticoids and non-steroidal anti-inflammatory drugs showed signals of harm due to their non-specific effects. Other broad inhibitors, e.g., methotrexate, cyclosporine, or colchicine, did not improve clinical outcomes as acute therapies for MI. Specific inhibitors of the complement cascade, adhesion molecules, or inflammatory mediators were mostly disappointing in humans. However, an interleukin-1 inhibitor (anakinra) and a matrix metalloproteinase inhibitor (doxycycline) improved clinical outcomes in patients with AMI. Promising RNAse1, anti-toll-like receptor 2 antibodies, and inflammasome inhibitors still need to be tested in humans. Finally, positive results should be replicated in large clinical trials before they can be implemented into the standard AMI therapy.