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Pitfalls and Misinterpretations of Cardiac Findings on PET/CT Imaging: A Careful Look at the Heart in Oncology Patients.
Betancourt Cuellar, SL, Palacio, D, Benveniste, MF, Carter, BW, Gladish, G
Current problems in diagnostic radiology. 2019;(2):172-183
Abstract
Positron emission tomography (PET) computed tomography (CT) with 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) has been established as an effective modality for evaluation of cancer. Interpretations of patterns of physiologic 18F-FDG uptake by the heart is particularly difficult given the wide normal variations of 18F-FDG metabolic activity observed. Atypical patterns of focal or diffuse physiologic cardiac 18F-FDG uptake and post-therapeutic effects after radiation therapy, systemic diseases, or cardiomyopathy may also be confused with malignant disease on 18F-FDG PET/CT. In this article, we review the variations of normal cardiac 18F-FDG uptake observed in oncology patients and the appearances of other patterns of pathologic metabolic activity, related or not related to the malignancy being investigated, that may lead to false-negative and false-positive results.
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The Impact of Emerging Bioconjugation Chemistries on Radiopharmaceuticals.
Fay, R, Holland, JP
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(5):587-591
Abstract
The use of radiolabeled antibodies, immunoglobulin fragments, and other proteins are an increasingly important sector of research for diagnostic imaging and targeted radiotherapy in nuclear medicine. As with all radiopharmaceuticals, efficient radiochemistry is a prerequisite to clinical translation. For proteins, variations in the primary amino acid sequence, the secondary structures, and tertiary folds, as well as differences in the size, charge, polarity, lipophilicity, and the presence of posttranslational modifications, add complexity to the system. The choice of radionuclide or chelate, and its impact on the thermodynamic, kinetic, and metabolic stability of a radiotracer, has attracted much attention but the chemistry by which the radionuclide is conjugated to the protein scaffold is of equal importance. Recently, a wealth of creative advances in protein ligation methods based on chemical, photochemical, and enzyme-mediated processes has emerged. As radiochemists explore alternative bioconjugation strategies, this article considers their potential impact on radiotracer design.
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Impacto de la medicina nuclear en el diagnóstico y tratamiento del cáncer diferenciado de tiroides.
Medina-Ornelas, S, García-Pérez, F, Granados-García, M
Gaceta medica de Mexico. 2018;(4):509-519
Abstract
Los pacientes afectados por el cáncer diferenciado de tiroides habitualmente presentan un curso clínico favorable, ya que la piedra angular del tratamiento es la cirugía; a pesar de esto, algunos pueden desarrollar un ominoso desenlace, debido a las características clinico-patológicas de esta enfermedad. El tratamiento óptimo aún es controvertido, en especial respecto a la extensión de la cirugía, indicaciones de radioyodo y la supresión de la hormona estimulante de la tiroides. La correcta evaluación de los riesgos, antes y después de la cirugía, facilita un selectivo enfoque del tratamiento; destacando la relevancia de revisar el impacto de la medicina nuclear en la correcta evaluación, tratamiento y seguimiento de los pacientes que padecen esta neoplasia. Patients affected by differentiated thyroid cancer usually have a favorable clinical course, since the cornerstone of treatment is surgery; despite this, some patients may develop an ominous outcome, due to the clinical-pathological features of this disease. Optimal treatment remains controversial, especially regarding the extent of surgery, indications for radioiodine and thyroid-stimulating hormone. The correct evaluation of risks before and after surgery facilitates a selective treatment approach; highlighting the importance of reviewing the impact of nuclear medicine on the correct evaluation, treatment and follow-up of patients suffering from this neoplasm.
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4.
Hypervalent aryliodine compounds as precursors for radiofluorination.
Pike, VW
Journal of labelled compounds & radiopharmaceuticals. 2018;(3):196-227
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Abstract
Over the last 2 decades or so, hypervalent iodine compounds, such as diaryliodonium salts and aryliodonium ylides, have emerged as useful precursors for labeling homoarenes and heteroarenes with no-carrier-added cyclotron-produced [18 F]fluoride ion (t1/2 = 109.8 min). They permit rapid and effective radiofluorination at electron-rich as well as electron-deficient aryl rings, and often with unrestricted choice of ring position. Consequently, hypervalent aryliodine compounds have found special utility as precursors to various small-molecule 18 F-labeling synthons and to many radiotracers for biomedical imaging with positron emission tomography. This review summarizes this advance in radiofluorination chemistry, with emphasis on precursor synthesis, radiofluorination mechanism, method scope, and method application.
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Will 68Ga PSMA-radioligands be the only choice for nuclear medicine in prostate cancer in the near future? A clinical update.
Cuccurullo, V, di Stasio, GD, Evangelista, L, Ciarmiello, A, Mansi, L
Revista espanola de medicina nuclear e imagen molecular. 2018;(2):103-109
Abstract
Prostate Cancer (PCa) represents the most common malignant tumor in men but according to the European Association of Urology (EAU) guidelines, a mass screening for PCa diagnosis should not be performed due to over-diagnosis and over-treatment related problems. An early clinical diagnosis is possible, mainly based on digital rectal examination and Prostatic Specific Agent (PSA) testing. However, the only mandatory test to define the presence of PCa is ultrasound guided-biopsy, obtained on multiple samples, which has also a high prognostic value. In this context, diagnostic imaging plays an important role as confirmed by EAU that in a 2016 update of their guidelines on PCa stated the importance of Positron Emission Tomography (PET) with 11C- or 18F-choline combined with computed tomography (CT) to identify local relapse, lymph node involvement and metastatic spread at all stages. Consequently, in 2017, the European Association of Nuclear Medicine (EANM) together with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) published new guidelines for 68Ga-Prostate Specific Membrane Antigen (PSMA) PET/CT to help physicians in the recommendation, execution and interpretation of PET/CT scans in patients with PCa. Thus, the aim of this 'evidence paper' is to define the current diagnostic algorithm in PCa in order to increase the general level of confidence in approaching such a crucial topic.
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Site-specific chelator-antibody conjugation for PET and SPECT imaging with radiometals.
Morais, M, Ma, MT
Drug discovery today. Technologies. 2018;:91-104
Abstract
Antibodies and their derivatives radiolabelled with positron- and gamma-emitting radiometals enable sensitive and quantitative molecular Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging of antibody distribution in vivo. Chelators that are covalently attached to antibodies allow radiolabelling with metallic PET and SPECT radioisotopes. Conventional strategies for chelator-protein conjugation generate heterogeneous mixtures of bioconjugates that can exhibit reduced affinity for their receptor targets, and undesirable biodistribution and pharmacokinetics. Recent advances in bioconjugation technology enable site-specific modification to generate well-defined constructs with superior properties. Herein we survey existing site-specific chelator-protein conjugation methods. These include chelator attachment to cysteines/disulfide bonds or the glycan region of the antibody, enzyme-mediated chelator conjugation, and incorporation of sequences of amino acids that chelate the radiometal. Such technology will allow better use of PET and SPECT imaging in the development of antibody-based therapies.
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Bone-targeted therapies to reduce skeletal morbidity in prostate cancer.
Dorff, TB, Agarwal, N
Asian journal of andrology. 2018;(3):215-220
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Abstract
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
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Merits of FDG PET/CT and Functional Molecular Imaging Over Anatomic Imaging With Echocardiography and CT Angiography for the Diagnosis of Cardiac Device Infections.
Chen, W, Sajadi, MM, Dilsizian, V
JACC. Cardiovascular imaging. 2018;(11):1679-1691
Abstract
The diagnosis of cardiac device infections, particularly device-related endocarditis, is challenging. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is based on in vivo FDG targeting of the pre-existing inflammatory cells at an infectious site. Hence, it is able to identify cardiac device infection early, before the development of morphological damages from the infectious process. Transesophageal echocardiography (TEE) and electrocardiographically gated computed tomographic angiography (CTA) are currently the first-line imaging studies for device-related endocarditis, but their application to evaluate the extracardiac components or sources of primary infection and/or emboli is limited. Functional FDG PET/CT may have unique advantages over the anatomically based TEE and CT or CTA in the following settings: 1) diagnosing infection earlier than TEE and CTA, before morphological damage ensues; 2) identifying prosthetic endocarditis when findings on TEE and CTA are inconclusive; 3) evaluating infection in the extracardiac components of devices; 4) detecting unexpected source of the primary infection; and 5) discovering embolic consequences of endocarditis in the body. All of these findings may ultimately affect patient management. Although the nonspecific nature of FDG is a concern in differentiating infection from inflammation, accurate diagnosis of infection can be reasonably achieved on the basis of FDG distribution pattern and clinical history or by adding radiolabeled white blood cell scan to improve specificity. Recent publications support the judicious use of FDG PET/CT, particularly in patients with inconclusive or negative results on initial echocardiography and CT.
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Parameters of metabolic quantification in clinical practice. Is it now time to include them in reports?
Mucientes, J, Calles, L, Rodríguez, B, Mitjavila, M
Revista espanola de medicina nuclear e imagen molecular. 2018;(4):264-270
Abstract
Qualitative techniques have traditionally been the standard for the diagnostic assessment with 18F-FDG PET studies. Since the introduction of the technique, quantitative parameters have been sought, more accurate and with better diagnostic precision, that may offer relevant information of the behavior, aggressiveness or prognosis of tumors. Nowadays, more and more studies with high quality evidence show the utility of other metabolic parameters different from the SUV maximum, which despite being widely used in clinical practice is controversial and many physicians still do not know its real meaning. The objective of this paper has been to review the key concepts of these metabolic parameters that could be relevant in normal practice in the future. It has been seen that there is more evidence in the complete evaluation of the metabolism of a lesion, through volumetric parameters that more adequately reflect the patient's tumor burden. Basically, these parameters calculate the volume of tumor that fulfills certain characteristics. A software available in the majority of the workstations has been used for this purpose and it has allowed to calculate these volumes using more or less complex criteria. The simplest threshold-based segmentation methods are available in most equipments, they are easy to calculate and they have been shown in many studies to have an important prognostic significance.
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The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology.
Irimie, A, Piciu, D
Current radiopharmaceuticals. 2017;(3):146-154
Abstract
BACKGROUND AND OBJECTIVE The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. METHODS We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. RESULTS Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. CONCLUSION The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option.