Seminars in Nuclear Medicine RSS feed: Current Issue. Seminars in Nuclear Medicine is a timely source for new concepts and techniques in nuclear medicine. The clinically oriented articles provide a reference for those involved in the performance and interpretation of nuclear medicine procedures. The contributing authors represent many of the recognized authorities from around the world. 2012 Topics , Volume 42, Issues 1-6 January Planar Imaging in the Age of SPECT March Functional Studies of the Gastrointestinal Tract May Theranostics July Low-Sensitivity FDG-PET Studiess September Radiation Oncology and Nuclear Medicine November Brain Imaging Update http://www.seminarsinnuclearmedicine.com/?rss=yesElsevier Inc.en © 2012 Elsevier Inc. All rights reserved. Seminars in Nuclear Medicine0001-2998423May 2012 © 2012 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.seminarsinnuclearmedicine.com/article/PIIS0001299812000025/abstract?rss=yesWe have decided to devote this issue of Seminars to a subject that many of you may have either not heard of, or are just becoming familiar. That subject is theranostics. The concept of theranostics is to promote an individualized approach to medical therapy and diagnosis. Under ideal circumstances the diagnostician uses an agent that is highly specific for diagnosing the entity afflicting the individual. The therapist then utilizes a variation of the same agent so that the same disorder with which the physician is dealing and from which the patient is suffering is treated with maximum efficiency and minimum complications.Letter from the Editors: TheranosticsLeonard M. Freeman, M. Donald Blaufox10.1053/j.semnuclmed.2012.01.001Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0145146http://www.seminarsinnuclearmedicine.com/article/PIIS0001299811001784/abstract?rss=yes Although the term has been coined recently, the concepts underlying theranosis have been applied in patient care for more than one-half century. However, advanced technologies are used now. Theranosis describes processes used to tailor therapy for a patient. It is the use of diagnostic tests to identify those patients better-suited for a drug (or drugs) or to determine how well a drug is working. 131I-iodide for imaging and for therapy of hyperthyroidism and thyroid cancer is an excellent example of personalized theranosis and has withstood challenge for more than 50 years. Radioimmunotherapy for non-Hodgkin lymphoma is a more recent example of theranosis. Either of 2 anti-CD20 monoclonal antibodies, one labeled with indium for imaging or 90Y for radiotherapy or a second labeled with 131I for both imaging and radiotherapy, is used for salvage and first-line therapy of multifocal non-Hodgkin lymphoma. The efficacy of these drugs is greater than that of alternative therapies. To mimic the molecular specificity and cell selectivity of a monoclonal antibody, smaller molecules that also bind to proteins upregulated by malignant cells can be used to transport cytotoxic agents to the malignant cells. Smaller carrier molecules like peptides, aptamers, affibodies, and selective, high-affinity ligands facilitate intensification of therapy because of their size. Personalized genomics, proteomics, and molecular imaging are among technologies currently used for theranosis. Molecular emission tomographic imaging with radiolabeled drugs has been used to examine the pharmacology of anticancer therapies and their effectiveness. Increased glycolysis, a molecular phenotype of many malignancies, can be imaged using 18F-fluoro-2-deoxyglucose (FDG). Tomographic imaging using FDG allows stratification of patients into those responding and likely to respond to the therapy and those better treated in another manner. Prediction of therapeutic response avoids useless therapy so that FDG imaging is included in official response evaluation criteria. Although a fixed approach to therapy may be more practical, an individualized approach is more likely to ensure that each patient receives an effective drug and drug dose that has acceptable and definable tissue effects. Drugs that work in one individual may be ineffective or cause adverse events in others. Concepts, Consequences, and Implications of TheranosisGerald L. DeNardo, Sally J. DeNardo10.1053/j.semnuclmed.2011.12.003Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0147150http://www.seminarsinnuclearmedicine.com/article/PIIS0001299811001796/abstract?rss=yes This article reintroduces and reinforces our proposed paradigm that involves specific individual “dual-purpose” radionuclides or radionuclide pairs with emissions suitable for both imaging and therapy and which, when molecularly (selectively) targeted using appropriate carriers, would allow pretherapy low-dose imaging as well as higher-dose therapy in the same patient. We have made an attempt to sort out and organize a number of such theragnostic radionuclides and radionuclide pairs that may thus potentially bring us closer to the age-long dream of personalized medicine for performing tailored low-dose molecular imaging (single-photon emission computed tomography/computed tomography or positron emission tomography/CT) to provide the necessary pretherapy information on biodistribution, dosimetry, the limiting or critical organ or tissue, the maximum tolerated dose, and so forth, followed by performing higher-dose targeted molecular therapy in the same patient with the same radiopharmaceutical. Beginning in the 1980s, our work at Brookhaven National Laboratory with such a “dual-purpose” radionuclide, tin-117m, convinced us that it is arguably one of the most promising theragnostic radionuclides, and we have continued to concentrate on this effort. Our results with this radionuclide are therefore covered in somewhat greater detail in this publication. A major problem that continues to be addressed, but remains yet to be fully resolved, is the lack of availability, in sufficient quantities, of a majority of the best candidate theragnostic radionuclides in a no-carrier-added form. A brief description of the recently developed new or modified methods at Brookhaven National Laboratory for the production of 5 theragnostic radionuclide/radionuclide pair items, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer and other therapies, is provided. Paving the Way to Personalized Medicine: Production of Some Promising Theragnostic Radionuclides at Brookhaven National LaboratorySuresh C. Srivastava10.1053/j.semnuclmed.2011.12.004Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0151163http://www.seminarsinnuclearmedicine.com/article/PIIS0001299811001668/abstract?rss=yes Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, 128I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. 130I and 131I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, 131I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with 131I again the radioisotope of choice, although there were short-lived attempts to employ 125I and 132I for this purpose. 123I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy 124I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas 123I and 131I are employed in the staging and detection of functioning thyroid cancer. 124I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in 131I therapy of tumor heterogeneity, tumor hypoxia, and kinetics must be overcome, and long-term outcome studies following 131I given based on this new dosimetry must be completed before the nuclear medicine community will be able to predictably cure our thyroid cancer patients with this technology. Radioiodine: The Classic Theranostic AgentEdward B. Silberstein10.1053/j.semnuclmed.2011.12.002Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0164170http://www.seminarsinnuclearmedicine.com/article/PIIS0001299811001577/abstract?rss=yes Since 1981, meta-iodobenzylguanidine (MIBG), labeled with 131I and later 123I, has become a valuable agent in the diagnosis and therapy of a number of endocrine tumors. Initially, the agent located pheochromocytomas and paragangliomas (PGLs), both sporadic and familial, in multiple anatomic sites; surgeons were thereby guided to excisional therapies, which were previously difficult and sometimes impossible. The specificity in diagnosis has remained above 95%, but sensitivity has varied with the nature of the tumor: close to 90% for intra-adrenal pheochromocytomas but 70% or less for PGLs. For patients with neuroblastoma, carcinoid tumors, and medullary thyroid carcinoma, imaging with radiolabeled MIBG portrays important diagnostic evidence, but for these neoplasms, use has been primarily as an adjunct to therapy. Although diagnosis by radiolabeled MIBG has been supplemented and sometimes surpassed by newer scintigraphic agents, searches by this radiopharmaceutical remain indispensable for optimal care of some patients. The radiation imparted by concentrations of 131I-MIBG in malignant pheochromocytomas, PGLs, carcinoid tumors, and medullary thyroid carcinoma has reduced tumor volumes and lessened excretions of symptom-inflicting hormones, but its value as a therapeutic agent is being fulfilled primarily in attacks on neuroblastomas, which are scourges of children. Much promise has been found in tumor disappearance and prolonged survival of treated patients. The experiences with therapeutic 131I-MIBG have led to development of new tactics and strategies and to well-founded hopes for elimination of cancers. Radiolabeled MIBG is an exemplar of theranostics and remains a worthy agent for both diagnosis and therapy of endocrine tumors. Theranostics: Evolution of the Radiopharmaceutical Meta-Iodobenzylguanidine in Endocrine TumorsJames C. Sisson, Gregory A. Yanik10.1053/j.semnuclmed.2011.11.004Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0171184http://www.seminarsinnuclearmedicine.com/article/PIIS0001299811001656/abstract?rss=yes 18F-2-deoxy-2-fluoro-d-glucose (18F-FDG, later referred to as 19FDG) has been extensively used in diagnostic positron emission tomography (PET) in oncology for many years. FDG is a glucose analog that is taken by cells in a similar fashion as glucose and is phosphorylated by hexokinase to 18F-FDG-6-phosphate but cannot undergo further glycolysis, and hence is trapped in the cell. Metastatic cancer remains a major cause of death men and women, surpassed only by heart disease. Despite the enormous research efforts resulting in emergence of novel drug candidates, there is little progress in improving the survival of patients with many types of solid tumors. Thus, novel therapies to combat metastatic cancer are urgently needed. With a physical half-life of almost 2 hours, 18F emits energetic positrons with high abundance (96%) and a path length in tissue of ∼0.1-0.2 cm. Theoretically, these positrons can kill cancer cells in the same manner as electrons by damaging DNA and cellular machinery and inducing apoptosis/necrosis of the tumor cells. Several years ago, we explored, in a first series of comprehensive studies, the therapeutic potential of FDG in experimental breast cancer and showed its efficacy and safety. Since then, FDG therapy has been shown to be effective and safe in experimental melanoma, colon cancer, as well as in eliminating in vitro the endothelial cells in blood vessels, which supply the tumors with nutrients. The next step forward in translation of FDG therapy into the clinic should be a phase II clinical trial. Also, recent developments in targeted PET imaging could increase the range of PET pharmaceuticals potentially useful for positron therapy of metastatic cancers because of increased specificity of these tracers in comparison with FDG. FDG for Therapy of Metabolically Active TumorsSridivya Jaini, Ekaterina Dadachova10.1053/j.semnuclmed.2011.12.001Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0185189http://www.seminarsinnuclearmedicine.com/article/PIIS0001299812000037/abstract?rss=yes Theranostics of neuroendocrine neoplasms (NENs) based on molecular imaging using receptor positron emission tomography/computed tomography (PET/CT) with 68Ga-labeled somatostatin (SMS) analogs and molecular radiotherapy applying peptide receptor radionuclide therapy (PRRNT) with 90Y- and/or 177Lu-labeled peptides has paved the way to personalized medicine. SMS receptor PET/CT enables very accurate detection of NENs and their metastases with high diagnostic sensitivity and specificity and provides quantitative, reproducible data that can be used for selecting patients for PRRNT and evaluation of therapy response. Among other advantages are the fast imaging protocol (total study time, 60-90 minutes), low radiation burden (10-12 mSv), flexibility in daily use, and lower cost than octreotide scintigraphy. As we move toward personalized medicine, the diagnostic information obtained from PET/CT must be improved, that is, by fast routine quantification of lesions. PRRNT is highly effective for the treatment of NENs, even in very advanced cases, and lends a benefit in overall survival of several years. In addition, significant improvement in clinical symptoms and excellent palliation can be achieved. In patients with progressive NENs, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period (Bad Berka Concept) results in good therapeutic responses. By this concept, severe hematologic and/or renal toxicity can be reduced or completely avoided, and the quality of life can be improved. Sequential (DUO-PRRNT) and concurrent (TANDEM-PRRNT) administrations of radiopeptides are more effective in progressive NEN than using either radionuclide alone. PRRNT should only be performed at specialized centers, as NEN patients need highly individualized interdisciplinary treatment and long-term care. Peptides and Receptors in Image-Guided Therapy: Theranostics for Neuroendocrine NeoplasmsRichard P. Baum, Harshad R. Kulkarni, Cecilia Carreras10.1053/j.semnuclmed.2012.01.002Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0190207http://www.seminarsinnuclearmedicine.com/article/PIIS0001299811001565/abstract?rss=yes The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images. Accuracy and Precision of Radioactivity Quantification in Nuclear Medicine ImagesEric C. Frey, John L. Humm, Michael Ljungberg10.1053/j.semnuclmed.2011.11.003Seminars in Nuclear Medicine 42, 3 (2012)2012-05-01Seminars in Nuclear Medicine2012-05-01423S0001-2998(11)X0009-0208218