Search

Molecular targeting requires assessing several factors that come into play such as the location of the target, the choice of radionuclide, the inertness of the bifunctional chelate and stability of the covalently bound halogens, matching the residence time in the tumor with the physical half-life of the radionuclide, the scale and scope of the disease, and the absorbed dose sensitivity of the targeted tumor compared to normal tissue. The principles of molecular targeting are well established, but a paradigm shift from designing a medium-affinity radiotracer used to determine target density to designing a high-affinity, high-target density radioligand to maximize the target-to-nontarget ratio should increase the probability of detecting lesions smaller than the instrument resolution. Developing and validating a therapeutic radiopharmaceutical for a single target is necessary, but often not sufficient to produce a toxic event because of other mechanisms that are only partially understood. These include nontargeted effects due to radiation emitted from neighboring, targeted cells as well as bystander effects produced by the cellular processing of radiation not necessarily impinging on DNA. Both of these indirect consequences of cellular radiation could make a substantial contribution to the efficacy of targeted radionuclide therapy. These mechanisms should be exploited to optimize the efficacy of targeted radiotherapy and overcome the inefficiency of tumor control due to nonuniform distribution of radiation dose. The design approach to take advantage of the indirect consequences of cellular radiation depends heavily on further elucidation of the indirect effect. The successful combination of these two should lead to more effective nuclear radiotherapy.

The armamentarium of approved radiopharmaceuticals for either diagnosis or therapy is at the core of the clinical practice of today's nuclear medicine. Nevertheless, both because the currently approved agents do not meet all the clinical needs for radionuclide targeting and because advancing knowledge in the pathophysiology of tissues/organs opens in turn new opportunities, investigations continue at the preclinical and clinical validation level for the development of new radiopharmaceuticals, most of which are not approved yet for commercial use. Concerning in particular the diagnostic applications of nuclear medicine to oncology, ongoing investigations in the search for tumor-targeting agents with better specificity and sensitivity are countless, possibly within the scenario of theranostics-that is, with the dual potential for imaging and for therapy, depending on the specific radionuclide employed for radiolabeling. We will focus this chapter on the most promising imaging agents labeled with single-photon-emitting radionuclides based on some of the mechanisms that are typical for tumor cells/tissues.

Leukemias are a group of acute and chronic hematological neoplasias characterized by the dissemination of cancer cells originating in the bone marrow via the bloodstream. In 2016, the estimated number of new leukemia cases was more than 110,000 in all of Europe and 47,000 in the USA. Leukemia is the cause of 4% of all cancer deaths and accounts for 3.6% of all cancers. Historically, leukemias have been divided into four major categories further classified into subtypes based on specific features of cells: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML). A revised classification of myeloid/lymphoid neoplasms and leukemias has recently been published to better characterize each disease. This updated classification incorporated new scientific and clinical information to refine diagnostic criteria for previously described neoplasms and introduced newly recognized disease entities. In this chapter, the main entities of leukemia, with specific regard to imaging for diagnosis, treatment response assessment, and follow-up, will be treated according to what is reported in the clinical guidelines.

Monoclonal antibodies (MAbs) raised against cancer antigens may mediate antibody-dependent cell-mediated cytotoxicity. This form of cancer control arises from cytolysis of a target cell by effector lymphocytes, such as cytotoxic T lymphocytes or natural killer cells. However, most of these antibodies have low/moderate efficacy in the tumor control. Antibodies targeting hormone receptors expressed by cancer have shown greater tumor control compared with other cell membrane targets. Moreover, the labeling of these antibodies with a toxin can potentiate their efficacy in the tumor control. In this way, the antibody becomes an invaluable targeting vector for delivery of the toxin to the cancer cells. The toxin/antibody complex is called the immunoconjugate. Different molecules, chemicals, or radioisotopes can serve themselves as toxins; toxins may have long half-lives in the body (e.g., ricin), thus increasing the toxicity to both the cancer and normal tissues. However, the different radioisotopes (e.g., iodine-131, lutetium-177) have a wide range of half-lives and radiation decay that make them useful for different applications. Beta-emitting radioisotopes, predominantly I-131, have had only modest success in radioimmunotherapy. More recently, high linear energy transfer (LET) radiation in the form of alpha particles has been studied: alpha radiation is ideal for killing isolated cancer cells in transit in the vascular and lymphatic systems and regressing tumors by disruption of tumor capillary networks by targeting and killing tumor capillary endothelial cells. Over the past 20 years the development of alpha-immunoconjugates has enabled targeted alpha therapy (TAT) to progress from in vitro studies, through in vivo experiments, to clinical trials. The dose to normal tissues always provides a limitation to the injected dose and that received by the tumor. However, TAT can achieve cancer regression within the maximum tolerance dose for normal tissue. TAT was originally

Radiopharmaceuticals contain a radionuclide and an agent to direct the radionuclide to a receptor, antigen, ionic pump, or other sites of interest. Some radiopharmaceuticals are simple, such as the ionic form of the radionuclide, while most radiopharmaceuticals have a complex chemical structure where the radionuclide provides a signal, indicating the site of localization of the carrier molecule. Common single-photon radiopharmaceuticals used for oncological diagnosis include the agents labeled with 99mTc such as 99mTc-bisphosphonates (that accumulate at sites of bone mineral deposition), 99mTc-labeled colloids (that are used for lymphoscintigraphy and for imaging of the liver and spleen), 99mTc-hexakis-methoxy-isobutyl-isonitrile, and 99mTc-tetrofosmin (initially employed for myocardial perfusion imaging, and also used for localization of parathyroid adenomas and for identification of other malignant tumors). The most commonly used radiopharmaceuticals labeled with radioiodine (123I or 131I) include iodide itself (for localization of thyroid tissue) and the catecholamine analog metaiodobenzylguanidine (MIBG, for localizing pheochromocytoma and neuroblastoma). Thallium-201 chloride (201Tl) is used for myocardial perfusion imaging as well as tumor perfusion imaging, while 111In-pentetreotide detects overexpression of somatostatin receptors, especially in neuroendocrine tumors and in lesions arising from the neural crest, such as carcinoid, paragangliomas, and medullary thyroid carcinomas. 111In-capromab pendetide is a murine monoclonal antibody recognizing a transmembrane glycoprotein expressed by poorly differentiated and metastatic prostate adenocarcinomas. 67Ga-citrate receptors are overexpressed on membranes of both tumor and inflammatory cells.

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in

BACKGROUND ‘Splenosis’ is defined as the autotransplantation of splenic tissue following trauma or surgery, usually in the form of intraperitoneal nodules. The proliferation of imaging techniques has resulted in increased unexpected discoveries of splenosis nodules, and achieving a differential diagnosis can be challenging. Nuclear medicine studies have been playing an increasingly important role in this process, but the clinical significance of asymptomatic nodules remains uncertain. CASE SUMMARY We present a case of pelvic splenosis in a 73-year-old man diagnosed 56 years after a splenectomy during a computed tomography (CT) follow-up for B-cell lymphoma, presenting intense contrast enhancement of an 18 mm nodule in the right recto-vesical space. 18F-fluorodeoxyglucose demonstrated weak metabolic activity. Since histological diagnosis was deemed necessary, the nodule was easily removed with robotically assisted laparoscopy, together with another 6 mm left a paracolic lesion. The latter was previously undiagnosed but retrospectively visible on the CT scan. CONCLUSION In a patient requiring differential diagnosis of splenosis nodules from lymphoma recurrence, the robotic approach provided a safe en bloc removal with short hospitalization. The Da Vinci Xi robot was particularly helpful because its optics can be introduced from all ports, facilitating visualization and lysis of multiple intra-abdominal adhesions

Cardiovascular infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient’s management, as early treatment improves the prognosis. Cardiovascular infections are difficult to diagnose on the basis of a single symptom, sign, or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data, and imaging data. The application of multimodality imaging, including molecular imaging techniques, has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices, while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. This chapter describes the main epidemiological, clinical, and diagnostic challenges in infective endocarditis and infections associated with cardiovascular implantable electronic devices, with particular regard to the role of WBC SPECT/CT and [18F]FDG PET/CT in each diagnostic algorithm. In addition, the needs of proper hybrid equipment, dedicated imaging acquisition protocols, specific expertise for imaging reading and imaging interpretations in this field are discussed, emphasizing the need of a specific reference framework within a cardiovascular multidisciplinary team approach.

The use of implantable medical devices has increased in “modern” medical and surgical practice, and the rate of their infections is variable, depending on the type of device and the population risk profile. The overall risk of device-related infection across the population is around 1%, but it might be significantly increased in specific populations as vulnerability to microbial pathogens increases in elderly, immuno-compromised, and hospitalized patients. Device-related infection results from the multifaceted interaction of bacterial, device, and host factor. Multiresistant nosocomial pathogens are the most common organisms colonizing the surface of devices, and a full understanding of how a biofilm formation is crucial to understand the pathogenesis of their infection and define the most suitable treatment. This chapter describes the most relevant implantable medical devices of interest to nuclear medicine and the corresponding diagnostic strategy for each of them with particular regard to the role of nuclear medicine procedure in the diagnostic algorithm.

Cardiovascular infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient management, as early treatment improves the prognosis, hardly diagnosed on the basis of a single symptom, sign or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data and imaging data. The application of multimodality imaging, including molecular imaging techniques, has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this chapter, we describe data supporting the use of a multimodality and multidisciplinary approach to cardiovascular infections. In particular, the role of WBC SPECT/CT and [18F]FDG PET/CT in most prevalent and clinically relevant cardiovascular infections is discussed.

The lymphatic circulation is part of the peripheral circulation, linking blood circulation at its origins (the interstitial space) and at its final drainage point (the thoracic duct). The lymphatic system includes fluid (lymph), the lymphatic vessels, the lymph nodes (stations along the drainage route where fluid and cell exchange between blood and lymph occur), and other lymphoid tissue, particularly the spleen and bone marrow. The lymphatic system has a significant role in maintaining the balance of tissue fluid volume and an appropriate cellular chemical environment (the capillary plasma filtration process). An important role of the lymphatic circulation is the transport of the antigen and immune cells from peripheral tissues to lymph nodes. The interaction between lymphatic endothelial cells and leukocytes controls the immune cell migration and immune responses by regulating lymphatic flow and various secreted molecules such as chemokines and cytokines in tissue. Components of the lymphatic system include cells, vessels, and fluids. The lymphatic system is integrated with the hematopoietic and neurohormonal systems and can be divided into peripheral (from the interstitial space to and within the nearest lymph node) and central (efferent lymphatics, cisterna chyli, and thoracic duct, all lymphatic organs).

Lymphomas are hematologic malignancies characterized by abnormal proliferation of lymphoid cells, most commonly arising in lymph nodes, but potentially involving any organ or tissue in the body. Several classification systems have been proposed for lymphomas. Classification of a lymphoma under a certain category can affect treatment and prognosis. Common features considered for classifying lymphomas generally include: (i) whether or not it is a Hodgkin lymphoma; (ii) whether the abnormally replicating cell is a T cell or B cell; and (iii) site where the malignant cell arises.Multiple myeloma (MM) is the most common primary bone cancer. The clonal proliferation of malignant plasma cells in the bone marrow may result both in local growth and in systemic effects due to the overproduction of a monoclonal protein (M-protein). Almost all patients evolve from an asymptomatic premalignant stage, termed monoclonal gammopathy of undetermined significance (MGUS), through the smoldering myeloma (SMM), and eventually to “malignant” MM. MM differs from MGUS and SMM by the presence of end-organ damage associated with a complex syndrome named CRAB. MM, MGUS and smoldering myeloma (SMM) are defined according to the updated version of the criteria for the diagnosis of plasma cell proliferative disorders established by the International Myeloma Working Group.

Early diagnosis and clinical staging in patients affected by malignant pleural mesothelioma (MPM) is necessary to manage individual therapy strategies. Computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used for non-invasive clinical staging. Because of the complex growth pattern of MPM, it is difficult to make a clinical judgement only with morphological imaging, so 18F-FDG PET-CT represent an important adjunctive imaging tool in these patients. 18F-FDG PET-CT can be useful in detecting malignant pleural mesothelioma in patients exposed to asbestos and distinguish asbestos-related benign lesions. Combined PET-CT is essential for selecting patients with resectable disease, increasing the detection of locally advanced tumour and improve the accuracy of preoperative staging. 18F-FDG PET-CT could be useful also in risk stratification, to avoid radical surgery in cases characterized by the worst prognosis. PET-CT is gradually becoming essential in assessment of tumour response in patients undergoing chemotherapy. Metabolic imaging analysis permits the early identification of non-responders to chemotherapy, avoiding unsuccessful treatment, characterized by important toxicities and high mortality risk.

Purpose: Cardiac transthyretin-related amyloidosis (ATTR) is a progressive and fatal cardiomyopathy. The diagnosis of this disease is frequently delayed or missed due to the limited specificity of echocardiography. An increasing amount of data in the literature demonstrate the ability of bone scintigraphy with bone-seeking radiopharmaceuticals to detect myocardial amyloid deposits, in particular in patients with ATTR. Therefore we performed a systematic review and bivariate meta-analysis of the diagnostic accuracy of bone scintigraphy in patients with suspected cardiac ATTR. Methods: A comprehensive computer literature search of studies published up to 30 November 2017 on the role of bone scintigraphy in patients with ATTR was performed using the following search algorithm: (a) “amyloid” OR “amyloidosis” AND (b) “TTR” OR “ATTR” OR “transthyretin” AND (c) “scintigraphy” OR “scan” OR “SPECT” OR “SPET” OR “bone” OR “skeletal” OR “skeleton” OR “PYP” OR “DPD” OR “HMDP” OR “MDP” OR “HDP”. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−) and diagnostic odds ratio (DOR) of bone scintigraphy were calculated. Results: The meta-analysis of six selected studies on bone scintigraphy in cardiac ATTR including 529 patients provided the following results: sensitivity 92.2% (95% CI 89–95%), specificity 95.4% (95% CI 77–99%), LR+ 7.02 (95% CI 3.42–14.4), LR− 0.09 (95% CI 0.06–0.14), and DOR 81.6 (95% CI 44–153). Mild heterogeneity was found among the selected studies. Conclusion: Our evidence-based data demonstrate that bone scintigraphy using technetium-labelled radiotracers provides very high diagnostic accuracy in the non-invasive assessment of cardiac ATTR.

Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous carcinoma with neuroendocrine differentiation. However, literature data about the use of somatostatin receptor positron emission tomography/computed tomography (PET/CT) imaging in MCC are limited and its role is not clearly stated.