The Journal of Nuclear Medicine最新文献

{"title":"How Many Theranostics Centers Will We Need in the United States?","authors":"J. Czernin, J. Calais","doi":"10.2967/jnumed.122.264144","DOIUrl":"https://doi.org/10.2967/jnumed.122.264144","url":null,"abstract":"Lutetium-177-PSMA-617 (PLUVICTO) has been approved by the U.S. Food and Drug Administration for patients with prostatespecific membrane antigen (PSMA)–positive metastatic castrationresistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy (1). This great success was enabled by the design, execution, and results of the VISION trial (2) and has been awaited with great excitement by patients, their families, and treatment teams. We have previously provided some simplified business forecasts for nuclear theranostics (3). We are expecting a high demand for prostate-specific membrane antigen (PSMA)–targeted molecular radiotherapy initially—a demand that will further increase as indications expand to earlier disease stages. The randomized phase 2 TheraP trial suggested that Lu-PSMA-617 may achieve better prostate-specific antigen responses and progression-free survival than taxanes (cabazitaxel) as second-line therapy in patients with metastatic castration-resistant prostate cancer who progress after docetaxel (4). Several other clinical trials exploring the role of PSMA-targeted molecular radiotherapy, ranging from the neoadjuvant setting to the hormone-sensitive setting to first-line therapy for metastatic castration-resistant prostate cancer, are ongoing or about to start (5). Theranostic centers will also take care of patients with thyroid cancer; neuroendocrine tumors, including paraganglioma and pheochromocytoma; and other cancer types in the future. How and where will we be able to provide the best care for our patients? First, we must establish competence. Implementing training and accreditation standards is an essential prerequisite. Two articles, one from experts in Australia and the other from the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the International Atomic Energy Agency, will soon be published in The Journal of Nuclear Medicine and provide guidance. Second, we must create a robust supply chain. Given the limited production capacities that are further at risk by the current geopolitical uncertainties, a robust supply chain of therapeutic isotopes is critically important. Failure to deliver therapies reliably will reliably deliver failure of the approach. This is both a challenge and an opportunity for industry and academia, as new production strategies could be developed jointly. Third, we must establish a large number of theranostic centers. The incidence of neuroendocrine tumors is increasing, being currently estimated at 12,000–15,000 new cases per year in the United States, with an estimated prevalence of 170,000 cases (6). Half the newly diagnosed patients will undergo surgery, but many will experience slowly progressing disease. As a conservative estimate, and assuming that late-stage rather than earlier-stage patients are treated, around 7,500 patients per year might benefit from therapy with Lu-DO","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87464189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine Clinical Trials","authors":"P. O'Dwyer, L. Kostakoglu","doi":"10.2967/jnumed.121.264320","DOIUrl":"https://doi.org/10.2967/jnumed.121.264320","url":null,"abstract":"Lale Kostakoglu, MD, MPH, a professor of Radiology and Chief of Nuclear Medicine and Molecular Imaging in the University of Virginia Health System (Charlottesville, VA), talked with Peter J. O’Dwyer, MD, a professor of Medicine at the University of Pennsylvania (Philadelphia) and a medical oncologist with expertise in gastrointestinal (GI) and pancreatic cancers. Dr. O’Dwyer has been the Group Co-Chair of the ECOG-ACRIN Cancer Research Group since May 2017. ECOG-ACRIN is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. The network includes more than 1,300 academic and community-based cancer centers and hospitals in the United States and around the world, with approximately 15,000 oncology professionals involved in sponsored research. Within ECOG-ACRIN, Dr. O’Dwyer co-chairs the landmark National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (MATCH) precision medicine cancer trial. He is the CEO and chair of the Board of Managers of PrECOG, LLC, and president of the ECOG Research and Education Foundation. Dr. O’Dwyer received his medical degree from the University of Dublin, Trinity College (Ireland), and completed his residency at the Hammersmith Hospital (London, U.K.). After a fellowship at the Baltimore Cancer Research Center (MD), he became a senior investigator in the Division of Cancer Treatment at NCI (Bethesda, MD). He previously led the Developmental Therapeutics Programs at Fox Chase Cancer Center (Philadelphia, PA) and the University of Pennsylvania. He has authored more than 350 scientific articles and participates in numerous national and international organizations. Dr. Kostakoglu: Let’s start with your inspiring trans-Atlantic experience. Would you like to tell us about your background and the pivotal decisions that shaped your career path? Dr. O’Dwyer: That’s an interesting question. Actually, my career path has been formed in the United States. I have links with Europe just because many of my colleagues through the years have gone from junior to more mature positions there, and a lot of research is based on personal links. We’re fortunate within ECOG-ACRIN to have a strong presence in Europe, South America, Asia, and Canada to establish new member relationships. Particularly in Asia, where South Korea is the most important country for us to focus on right now because we have shared studies there. It’s been difficult to go beyond that because of various regulatory issues, particularly in South America. To generate scientific ideas and design new trials, we often collaborate with global research consortia, such as the International Rare Cancers Initiative and others. I think these international interactions really help us focus on the global impact of our studies and assist us in carrying out ECOG-ACRIN’s strong commitment to advancing standards of care in broad populations of cancer patients and those at risk. We seek ","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91543716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Letter from Ukraine","authors":"K. Herrmann, Kmetyuk Yaroslav","doi":"10.2967/jnumed.122.264288","DOIUrl":"https://doi.org/10.2967/jnumed.122.264288","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85120848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome of Patients with PSMA PET/CT Screening Failure by VISION Criteria and Treated with 177Lu-PSMA: A Multicenter Retrospective Analysis","authors":"O. Sartor","doi":"10.2967/jnumed.122.264128","DOIUrl":"https://doi.org/10.2967/jnumed.122.264128","url":null,"abstract":"Selection of patients for treatment with prostate-specific membrane antigen (PSMA)–targeted therapy is somewhat controversial. There are those who have suggested that no selection is necessary and those who have suggested that tight imaging-based selection criteria are required. What is optimal, what is required, and what is practical are all different questions. Given the importance of the VISION trial (the only trial demonstrating overall survival benefit with PSMA-targeted therapy), findings in this trial will be examined in some detail (1). Of note, the VISION trial enrolled patients with at least 1 metastatic lesion present on baseline contrast-enhanced CT, MRI, or bone scanning obtained no more than 28 d before beginning study therapy. Thus, metastatic disease on conventional imaging was required. In addition, patients must have progressed after one or more androgen axis inhibitors (e.g., abiraterone, enzalutamide, darolutamide, or apalutamide) and at least one taxane-based chemotherapy. Approximately 41% of VISION participants were previously treated with 2 taxane regimens. What were the eligibility criteria relative to PSMA PET/CT imaging in VISION? First, all patients must have had a centrally read Ga-PSMA-11 PET/CT scan for trial entry. Second, a metastatic lesion (one or more) that was PSMA PET–positive was required. PSMA PET positivity was determined by uptake in the lesion at an intensity level greater than that in the liver. There was no SUV cutoff requirement; potential metastatic lesions in each patient were compared with liver uptake by a centralized PET reading. There were no size criteria for metastatic PSMA PET–positive lesions. Importantly, the patients screened for the VISION trial had additional imaging-based exclusion criteria. Patients were excluded if there were PSMA PET–negative lesions (uptake less than in liver) measuring at least 1 cm in solid organs, at least 2.5 cm in lymph nodes, or at least 1 cm in a bone lesion with a soft-tissue component. Assessment was by contrast-enhanced CT combined with the PET/CT findings. These negative selection criteria are quite important and helped to exclude patients harboring lesions with low levels of PSMA expression. During the VISION design phase, there was a strong desire to avoid using 2 PET scans as a requirement for trial entry, knowing that the VISION entry criteria would likely be cited by regulatory authorities considering Lu-PSMA-617 as an approved therapy. In the United States, and many other areas of the world, obtaining reimbursement for 2 distinct types of PET scans was deemed potentially problematic. Thus, for practical reasons, F-FDG PET scans were not used in the VISION entry criteria. In the plenary session at the 2021 American Society of Clinical Oncology meeting, the discussant questioned whether PSMA-based imaging was required for selection of patients (2). This discussion followed the initial presentation of the VISION trial. Of the 1,003 patients screened wi","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75737876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radionuclide Evaluation of Brain Death in the Post-McMath Era: Epilogue and Enigmata","authors":"L. Zuckier","doi":"10.2967/jnumed.122.263972","DOIUrl":"https://doi.org/10.2967/jnumed.122.263972","url":null,"abstract":"O n occasion, a patient ’ s medical odyssey emerges from obscu-rity into the public domain. Jahi McMath was an unfortunate 13-y-old girl who suffered a cardiac arrest after surgery and was subsequently declared dead by neurologic criteria (hereafter referred to as brain death [BD]). Her family successfully petitioned the courts to prevent interruption of supportive care. She was maintained on a ventilator for 4.5 y until experiencing cardiopulmonary arrest in June 2018. Because the profound and protracted legal arguments surrounding Jahi ’ s medical course resulted in extensive media coverage, many clinical details were disclosed in the public domain, which served as a nidus for editorials and reviews in the medical literature. An article on radionuclide evaluation of BD appeared in this journal in 2016, reviewing the initial course of Jahi McMath ’ s illness and discussing the role of scintigraphy in the determination of BD ( 1 ). Jahi ’ s entire medical records were released, including images from a radionuclide BD examination ( 2 ). This editorial updates the prior report by providing additional clinical history, radionuclide images and their analysis, and a discussion of controversy and questions engendered by this tragic case. Clinical information presented here is in the public domain, either in previously published literature or with per-mission granted by Jahi ’ s mother.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83213881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"18F-FDG Uptake in Brown Adipose Tissue After Exposure to the Cold: From Possible Pitfall in Early PET Scans to Metabolic Biomarker","authors":"P. Erba, A. Natali, H. Strauss, G. Mariani","doi":"10.2967/jnumed.122.264188","DOIUrl":"https://doi.org/10.2967/jnumed.122.264188","url":null,"abstract":"here are 3 types of fat in the human body: white, brown, and beige ( 1 ). White adipocytes deposit extra energy into triglycerides, whereas beige and brown adipocytes have the unique ability to convert mitochondrial energy into heat (rather than adenosine triphosphate) via uncoupling protein 1. Obesity, especially excess fat in tissue that is normally lean, increases the risk of cardiovascular disease ( 2 ). In addition to the amount of fat, the distribution of fat, especially increased abdominal fat, evaluated by the ratio of waist to hip circumfer-ences, predicts glucose intolerance, insulin resistance, hyperten-sion, and hypertriglyceridemia ( 3,4 ). PET/CT with 18 F-FDG provides a unique opportunity to view the metabolic activity of brown adipose tissue (BAT). However, even though visceral and subcutaneous fat are substantially less metabolically active than BAT, both are metabolically active tissues ( 5 ). Visceral adipose tissue is more metabolically active than subcutaneous fat. BAT is a thermoregulatory organ that consumes stored energy to produce heat through the expression of uncoupling protein 1. This phenomenon is called nonshivering thermogenesis and plays an important role in glucose and lipid metabolism ( 6 ). It is particularly intense in newborns, in whom it helps to maintain a","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79742111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Single-Time-Point Tumor Dosimetry Assuming Normal Distribution of Tumor Kinetics.","authors":"George Sgouros, Yuni K Dewaraja, Freddy Escorcia, Stephen A Graves, Thomas A Hope, Amir Iravani, Neeta Pandit-Taskar, Babak Saboury, Sara St James, Pat B Zanzonico","doi":"10.2967/jnumed.121.263717","DOIUrl":"10.2967/jnumed.121.263717","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72778260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total-Body PET: Will It Change Science and Practice?","authors":"Austin R Pantel, David A Mankoff, Joel S Karp","doi":"10.2967/jnumed.121.263481","DOIUrl":"10.2967/jnumed.121.263481","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84414897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagonlike Peptide-1 Receptor Imaging in Individuals with Type 2 Diabetes","authors":"Hsiaoju S Lee, L. States","doi":"10.2967/jnumed.121.263171","DOIUrl":"https://doi.org/10.2967/jnumed.121.263171","url":null,"abstract":"Radiolabeled exendin 4, the glucagonlike peptide-1 (GLP-1) receptor agonist, has great prospects for imaging and perhaps quantification of pancreatic b-cells. The GLP-1 receptor is found in high density in the pancreas and liver and plays a key role in postprandial blood glucose homeostasis, including stimulation of insulin synthesis and promotion of b-cell proliferation. b-cells constitute only a small volume of the pancreatic mass, comprising up to 2% of the pancreatic mass and 65%–80% of endocrine cells in the islets of Langerhans. A synthetic peptide agonist of the GLP-1 receptor, exendin-4, also known as exenatide, is used for the treatment of diabetes mellitus, making it an ideal peptide for radiotracer development (1,2). The desire to quantify b-cell mass has been a focus of radiotracer research since the initial first-in-humans studies by Boss et al., which have led to a variety of SPECT and PET radiotracers focused on different targets of glucose metabolism. Initially, Boss described a high-specificity and nanomolar-affinity radioiodinated tracer for the GLP-1 receptor (3). It is assumed from studies by Eng et al. that the GLP-1 receptor density reflects b-cell mass (4). Improvements in the spatial resolution and sensitivity of PET scanners have fueled the recent focus on PET radiotracers for this application. In this issue of The Journal of Nuclear Medicine, the article by Eriksson et al. (5) demonstrates a stepwise approach necessary for GLP-1receptor–targeting radiotracer development from the lab to the clinic. The authors investigated the utility of Ga-labeled 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetyl (DO3A)-exendin-4 (Ga-exendin4) in adults with type 2 diabetes (T2D) and its association with b-cell mass in overweight-to-obese T2D individuals, building on prior studies (6,7). Furthermore, the authors provided a simplified imaging protocol, a step toward higher throughput needed for large clinical trials. The strengths of this article include the description of preclinical data collected in vitro and in vivo using nonhuman primates. The in vitro studies define binding specificity and internalization characteristics and were followed by nonhuman primate studies evaluating dose escalation and self-blocking effect. The evaluation of biodistribution and physiology in nonhuman primates provided safety information and guidance for the application in human adults. In addition to the preclinical data, the authors also provided the initial evaluation in overweight-to-obese individuals. This study of 13 human subjects, 12 men and 1 woman, gives information on biodistribution and kinetics in the mostly male subjects. The results of this study show high pancreatic uptake compared with background activity. An unsuspected finding was variability in pancreatic radiotracer uptake across patients. This prompted further investigation, which revealed no association of uptake with pancreatic volume or patient age, as b-cell mass is thought t","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81780012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Cancer Research Priorities and the Role of Molecular Imaging","authors":"C. Van Dang, Elizabeth Jaffee, David Mankoff","doi":"10.2967/jnumed.122.264086","DOIUrl":"https://doi.org/10.2967/jnumed.122.264086","url":null,"abstract":"and Elizabeth Jaffee about their leadership in guiding national priorities for translational cancer research and their perspectives on the role of molecular imaging and theranostics.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85902650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}