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This book discusses the role of nuclear medicine in the diagnosis, staging, and treatment of patients with specific cancers. It presents the incidence, pathophysiologic and clinical aspects of the disease, the use of nuclear imaging in diagnosis, staging requirements, management of specific tumors, and surveillance after primary treatment of cancers. It addresses the various diagnostic/therapeutic options that are currently available or are most likely to become available in the near future according to a prioritized approach, thereby keeping to a minimum the number of diagnostic imaging procedures the patient is expected to undergo. Topics include basic science, clinical applications, radionuclide therapy, radioguided surgery, heart disease in the cancer patient, and adverse effects of cancer therapy. Each clinical chapter discusses the radionuclide procedures within an integrated framework, thereby identifying the information required for effective treatment of specific tumors. The book concludes with a series of updated cases that define and expand the didactic material in the clinical application chapters. Thoroughly updated and revised, the third edition incorporates new clinical evidence validating the use of radionuclides for diagnosis and therapy in oncology, new radiotracers, and the growing integration of imaging modalities into different types of hybrid imaging. With contributions from a group of internationally distinguished practitioners, Nuclear Oncology: From Pathophysiology to Clinical Applications, Third Edition, is a valuable reference for nuclear medicine physicians, radiologists, medical and surgical oncologists, and other clinicians involved in the care and management of cancer patients.

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.

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.

Disaggregation in optical networks is particularly relevant to be considered for the deployment of 5G services and towards the support of 6G. Particularly in the metro area network (MAN), this is especially crucial, as is the adoption of suitable photonic technologies enabling dense integration to design a sustainable network architecture. Furthermore, to dynamically allocate the ever-increasing traffic, supporting multiterabit capacity, an optimal usage of the available resources by properly exploiting the multiple dimensions (including the spectral and spatial ones), with programmable and adaptive data plane solutions, is key. In this work, we assess the capabilities of a disaggregated MAN that relies on new photonic devices, node architectures, and sliceable bandwidth/bit-rate-variable transceivers, approaching wavelength division multiplexing and space division multiplexing. A hierarchical network topology is attained and the feasibility of a cross-hierarchy optical continuum is demonstrated. In fact, we experimentally demonstrate the successful transmission of multiterabits/second capacity across multiple nodes corresponding to different hierarchy levels that have different implementation schemes and support different technologies. For the top tier hierarchy level nodes, we demonstrate the transmission of up to 8×11 = {88} spatial/spectral channels, for a total capacity of 1.676 Tb/s, employing a node architecture able to handle up to 2560 spatial/spectral channels at different aggregation levels and granularities.

Purpose: Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. Methods: Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). Results: Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64–0.92) and 0.80 (95% CI: 0.64–0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal t

Background: Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods: Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results: Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions

The origin of radiotherapy dates back to 1895-immediately after the discovery of X-rays. Since the beginning, efforts were focused on developing ways to improve the accuracy of radiation delivery. Molecular imaging allows the visualization of surrogates of several pathophysiological characteristics of tumor tissue (e.g., proliferation, metabolism, hypoxia, perfusion), allowing tailoring of dose distribution based on the tissue's features and biological patterns within the tumor. A significant improvement in the ability of modern radiotherapy to precisely target tumor while avoiding irradiating normal tissues can be achieved by integrating molecular imaging into an individualized radiation treatment planning. PET data are the most common molecular images used for tumor volume delineation and assessment of pathophysiological characteristics of tissue. The type of radiopharmaceutical used allows visualization and understanding of different pathophysiologic information. The most commonly used among all PET tracers is the 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). [18F]FDG is currently the mainstay of PET use in radiotherapy. With the aim of identifying specific biological tumor processes and offering valuable information that can assist radiation oncologist to modulate radiotherapy's doses and volumes, several other molecular imaging tracers emerged in the last few years. Non-[18F]FDG tracers commonly used in radiation oncology include [11C]Methionine ([11C]MET) for brain tumors; [18F]FDOPA for brain and neuroendocrine tumors; radiolabeled somatostatin analogs for somatostatin-receptor positive tumors; 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) and 18F-fluoromisonidazole (18F-FMISO) to identify regions of radiation resistance within the tumor; and [11C]/[18F]Choline, [18F]/68Ga-PSMA, and 18F-Fluciclovine for prostate cancer.

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.

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

On their way from inland to the ocean, flowing water bodies, their constituents and their biotic communities are exposed to complex transport and transformation processes. However, detailed process knowledge as revealed by Lagrangian measurements adjusted to travel time is rare in large rivers, in particular at hydrological extremes. To fill this gap, we investigated autotrophic processes, heterotrophic carbon utilization, and micropollutant concentrations applying a Lagrangian sampling design in a 600 km section of the River Elbe (Germany) at historically low discharge. Under base flow conditions, we expect the maximum intensity of instream processes and of point source impacts. Phytoplankton biomass and photosynthesis increased from upstream to downstream sites but maximum chlorophyll concentration was lower than at mean discharge. Concentrations of dissolved macronutrients decreased to almost complete phosphate depletion and low nitrate values. The longitudinal increase of bacterial abundance and production was less pronounced than in wetter years and bacterial community composition changed downstream. Molecular analyses revealed a longitudinal increase of many DOM components due to microbial production, whereas saturated lipid-like DOM, unsaturated aromatics and polyphenols, and some CHOS surfactants declined. In decomposition experiments, DOM components with high O/C ratios and high masses decreased whereas those with low O/C ratios, low masses, and high nitrogen content increased at all sites. Radiocarbon age analyses showed that DOC was relatively old (890–1870 years B.P.), whereas the mineralized fraction was much younger suggesting predominant oxidation of algal lysis products and exudates particularly at downstream sites. Micropollutants determining toxicity for algae (terbuthylazine, terbutryn, isoproturon and lenacil), hexachlorocyclohexanes and DDTs showed higher concentrations from the middle towards the downstream part but calculated toxicity was not

Rationale Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0–17.0 days and 16 days, 95% CI 13.8–18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71–1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74–2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42–1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.