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Radiopharmaceutical therapy (RPT) is a precision medicine approach that involves the targeted delivery of radioactive atoms to tumor cells, representing a breakthrough strategy for cancer treatment. Radiopharmaceuticals typically consist of a small amount of radioactive material, a radionuclide, paired with a chemical that specifically targets the cell. Some radionuclides naturally target specific cells or biological processes without the need for modification. RPT is a novel cancer treatment method that offers various advantages over current traditional treatment approaches. One of the primary advantages of RPT is its ability to target cancer cells, including those in metastatic areas. Another key advantage of RPT is that radiation can be delivered systemically, locally, or physiologically to specific cells internally rather than being applied externally. Moreover, radiotracer imaging can be utilized to determine radiopharmaceutical absorption in target tissues before providing a therapeutic dose. Compared to all other cancer treatment approaches, RPT has demonstrated high efficacy with minimal toxicity. The recent approval of multiple RPT medicines by the US Food and Drug Administration highlights the tremendous potential of this treatment. This article provides a detailed review of RPT, including insights into manufacturing procedures, safety measures, and its applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Radioligand therapy (RLT) is a targeted approach to treating cancer that has been shown to be safe and effective in a variety of disease states, including gastroenteropancreatic neuroendocrine tumors, lymphoma, and most recently, advanced prostate cancer. In the United States, patient access to this therapy is currently variable. Implementation of new RLT programs and expansion of existing programs are needed to broaden patient access to and standardize the delivery of RLT, especially as new therapies are introduced into clinical practice. Drawing from experience in establishing RLT programs in different settings, we have developed practical recommendations for building and implementing a robust RLT program. In this review, we present our recommendations for minimal requirements and optimal requirements, as well as system considerations, and special issues associated with implementing an RLT program in North American centers. [ABSTRACT FROM AUTHOR]

The goal of this article is to serve as a primer for the United States-based radiation oncologist who may be interested in learning more about radiopharmaceutical therapy (RPT). Specifically, we define RPT, review the data behind its current and anticipated indications, and discuss important regulatory considerations for incorporating it into clinical practice. RPT represents an opportunity for radiation oncologists to leverage 2 key areas of expertise, namely therapeutic radiation therapy and oncology, and apply them in a distinct context in collaboration with nuclear medicine and medical oncology colleagues. Although not every radiation oncologist will incorporate RPT into their day-to-day practice, it is important to understand the role for this modality and how it can be appropriately used in select patients. [ABSTRACT FROM AUTHOR]

Background: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification.Methods: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results.Results: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005).Conclusions: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging has become increasingly popular as a novel molecular imaging technique capable of improving the clinical management of patients with prostate cancer. To date, several 68Ga and 18F-labeled PSMA-targeted molecules have shown promising results in imaging patients with recurrent prostate cancer using PET/computed tomography (PET/CT). Studies of involving PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scintigraphy) and 11C/18F-choline PET/CT. In addition, PSMA-617 and PSMA I&T ligands can be labeled with α- and β-emitters (e.g., 225Ac, 90Y, and 177Lu) and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. Herein, we highlighted the current status of development and future perspectives of PSMA-targeted radiopharmaceuticals and their clinical applications. [ABSTRACT FROM AUTHOR]

Background and Objectives: Correct identification of estrogen receptor (ER) status in breast cancer (BC) is crucial to optimize treatment; however, standard of care, involving biopsy and immunohistochemistry (IHC), and other diagnostic tools such as 2-deoxy-2-[18F]fluoro-D-glucose or 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), can yield inconclusive results. 16α-[18F]fluoro-17β-fluoroestradiol ([18F]FES) can be a powerful tool, providing high diagnostic accuracy of ER-positive disease. The aim of this study was to estimate the budget impact and cost-effectiveness of adding [18F]FES PET/CT to biopsy/IHC in the determination of ER-positive status in metastatic (mBC) and recurrent breast cancer (rBC) in the United States (US)., Methods: An Excel-based decision tree, combined with a Markov model, was developed to estimate the economic consequences of adding [18F]FES PET/CT to biopsy/IHC for determining ER-positive status in mBC and rBC over 5 years. Scenario A, where the determination of ER-positive status is carried out solely through biopsy/IHC, was compared to scenario B, where [18F]FES PET/CT is used in addition to biopsy/IHC., Results: The proportion of true positive and true negative test results increased by 0.2 to 8.0 percent points in scenario B compared to scenario A, while re-biopsies were reduced by 94% to 100%. Scenario B resulted in cost savings up to 142 million dollars., Conclusions: Adding [18F]FES PET/CT to biopsy/IHC may increase the diagnostic accuracy of the ER status, especially when a tumor sample cannot be obtained, or the risk of a biopsy-related complication is high. Therefore, adding [18F]FES PET/CT to biopsy/IHC would have a positive impact on US clinical and economic outcomes., Competing Interests: RM-Y, AF-A, and ND are employees of GE HealthCare. KN and DG are employees of Certara Germany GmbH while Shereen Cynthia D’Cruz, Ph.D. an employee of Certara Synchrogenix. Certara is a consulting company that was paid by GE HealthCare for the services rendered. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Munter-Young et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Preoperative imaging before parathyroidectomy can localize adenomas and reduce unnecessary bilateral neck explorations. We hypothesized that (1) the utility of preoperative imaging varies substantially depending on the preoperative probability of having adenoma(s) and (2) that a selective imaging approach based on this probability could avoid unnecessary patient costs and radiation., Methods: We analyzed 3,577 patients who underwent parathyroidectomy for primary hyperparathyroidism from 2001 to 2022. The predicted probability of patients having single or double adenoma versus hyperplasia was estimated using logistic regression. We then estimated the relationship between the predicted probability of single/double adenoma and the likelihood that sestamibi or 4-dimensional computed tomography was helpful for operative planning. Current Medicare costs and published data on radiation dosing were used to calculate costs and radiation exposure from non-helpful imaging., Results: The mean age was 62 ± 13 years; 78% were women. Adenomas were associated with higher mean calcium (11.2 ± 0.74 mg/dL) and parathyroid hormone levels (140.6 ± 94 pg/mL) than hyperplasia (9.8 ± 0.52 mg/dL and 81.4 ± 66 pg/mL). The probability that imaging helped with operative planning increased from 12% to 65%, as the predicted probability of adenoma increased from 30% to 90%. For every 10,000 patients, a selective approach to imaging that considered the preoperative probability of having adenomas could save patients up to $3.4 million and >239,000 millisieverts of radiation., Conclusion: Rather than imaging all patients with primary hyperparathyroidism, a selective strategy that considers the probability of having adenomas could reduce costs and avoid excess radiation exposure., (Published by Elsevier Inc.)

Purpose: On June 13 to 14, 2019, the American Society for Radiation Oncology and the Radiological Society of North America convened a workshop on the treatment of oligometastatic disease in Washington, DC. The workshop was initiated for several reasons. First, oligometastatic disease is of increasing academic and community interest and has been identified by the American Society for Radiation Oncology membership as a top research priority. Second, emerging imaging and diagnostic technologies are more readily defining and detecting oligometastatic disease, making contemporary discussion of oligometastatic disease especially relevant. Third, radiosurgery and radiation in general are theorized to be ideal noninvasive therapy for the treatment of oligometastatic disease. Finally, innovations in targeted therapy and immune therapy have the potential to reverse widely disseminating disease into an oligometastatic state.Methods and Materials: The workshop was organized into 2 keynote addresses, 6 scientific sessions, and 3 group discussions during an end-of-workshop breakout session. New scientific work was presented in the form of 4 oral presentations and a poster session. Workshop participants were charged with attempting to answer 3 critical questions: (1) Can we refine the clinical and biological definitions of oligometastatic disease; (2) how can we better treat oligometastatic disease; and (3) what clinical trials are needed?Results: Here, we present the proceedings of the workshop.Conclusions: The clinical implications of improved treatment of oligometastatic disease are enormous and immediate. Radiation oncology and diagnostic radiology should rightly be at the forefront of the characterization and treatment of oligometastatic disease. Focused effort is required so that we can translate current efforts of large numbers of studies with few patients to larger studies of larger impact. [ABSTRACT FROM AUTHOR]

Purpose: In preclinical studies with rodent models of inflammatory diseases, [11C]CS1P1 has been identified as a promising imaging agent targeting sphingosine-1-phosphate receptor 1 (S1P1) in the central nervous system and other tissues. In preparation for USA Food and Drug Administration (FDA) approval of [11C]CS1P1 for human use, an acute biodistribution study in mice and an acute tolerability and toxicity evaluation in rats were conducted.Procedures: Acute organ biodistribution and excretion data was obtained using male and female Swiss Webster mice intravenously (IV) injected with 4.8-10 MBq of [11C]CS1P1. The organ residence times for each harvested organ were calculated using the animal biodistribution data, and were entered in the program OLINDA/EXM for C-11 to obtain human radiation dosimetry estimates. Acute tolerability and toxicity studies were conducted in male and female Sprague Dawley rats. Rats were administered an IV bolus of either the vehicle control or 0.3 mg/kg CS1P1. Blood samples were collected and a gross post-mortem examination was conducted at day 2 or day 15 post-injection.Results: The extrapolated human radiation dose estimates revealed that the highest organ dose was received by the liver with 24.05 μGy/MBq in males and 32.70 μGy/MBq in females. The effective dose (ED) estimates of [11C]CS1P1 were calculated at 3.5 μSv/MBq in males and 5.9 μSv/MBq in females. The acute tolerability and toxicity study identified 0.3 mg/kg as a no observable adverse effect level (NOAEL) dose, which is a ~ 300-fold dose multiple of the human equivalent dose of the mass to be injected for positron emission tomography (PET) imaging studies in humans as a no-observable-effect limit.Conclusions: The toxicity study in rats suggested that injection dose of radiotracer [11C]CS1P1 with mass amount < 10 μg is safe for performing a human PET study. The dosimetry data supported an injection of 0.74 GBq (20 mCi) dose for human studies would be acceptable. [ABSTRACT FROM AUTHOR]

The number of cases of dementia has dramatically increased over the last decade. Imaging of the brain with PET has been used for many years, but in the past decade the radiopharmaceuticals and technology available for imaging dementia have vastly improved. In recent years, the U.S. Food and Drug Administration has approved 3 PET radiopharmaceuticals for detecting amyloid in brain, and tau PET radiopharmaceuticals are being investigated in clinical trials for use in dementia imaging. This paper will discuss different forms of dementia that can be imaged with PET, review common radiopharmaceuticals used for imaging dementia, and provide technical recommendations for performing the studies. [ABSTRACT FROM AUTHOR]

Background: The rising global cancer burden has led to an increasing demand for imaging tests such as [ 18 F]fluorodeoxyglucose ([ 18 F]FDG)-PET-CT. To aid imaging specialists in dealing with high scan volumes, we aimed to train a deep learning artificial intelligence algorithm to classify [ 18 F]FDG-PET-CT scans of patients with lymphoma with or without hypermetabolic tumour sites., Methods: In this retrospective analysis we collected 16 583 [ 18 F]FDG-PET-CTs of 5072 patients with lymphoma who had undergone PET-CT before or after treatment at the Memorial Sloa Kettering Cancer Center, New York, NY, USA. Using maximum intensity projection (MIP), three dimensional (3D) PET, and 3D CT data, our ResNet34-based deep learning model (Lymphoma Artificial Reader System [LARS]) for [ 18 F]FDG-PET-CT binary classification (Deauville 1-3 vs 4-5), was trained on 80% of the dataset, and tested on 20% of this dataset. For external testing, 1000 [ 18 F]FDG-PET-CTs were obtained from a second centre (Medical University of Vienna, Vienna, Austria). Seven model variants were evaluated, including MIP-based LARS-avg (optimised for accuracy) and LARS-max (optimised for sensitivity), and 3D PET-CT-based LARS-ptct. Following expert curation, areas under the curve (AUCs), accuracies, sensitivities, and specificities were calculated., Findings: In the internal test cohort (3325 PET-CTs, 1012 patients), LARS-avg achieved an AUC of 0·949 (95% CI 0·942-0·956), accuracy of 0·890 (0·879-0·901), sensitivity of 0·868 (0·851-0·885), and specificity of 0·913 (0·899-0·925); LARS-max achieved an AUC of 0·949 (0·942-0·956), accuracy of 0·868 (0·858-0·879), sensitivity of 0·909 (0·896-0·924), and specificity of 0·826 (0·808-0·843); and LARS-ptct achieved an AUC of 0·939 (0·930-0·948), accuracy of 0·875 (0·864-0·887), sensitivity of 0·836 (0·817-0·855), and specificity of 0·915 (0·901-0·927). In the external test cohort (1000 PET-CTs, 503 patients), LARS-avg achieved an AUC of 0·953 (0·938-0·966), accuracy of 0·907 (0·888-0·925), sensitivity of 0·874 (0·843-0·904), and specificity of 0·949 (0·921-0·960); LARS-max achieved an AUC of 0·952 (0·937-0·965), accuracy of 0·898 (0·878-0·916), sensitivity of 0·899 (0·871-0·926), and specificity of 0·897 (0·871-0·922); and LARS-ptct achieved an AUC of 0·932 (0·915-0·948), accuracy of 0·870 (0·850-0·891), sensitivity of 0·827 (0·793-0·863), and specificity of 0·913 (0·889-0·937)., Interpretation: Deep learning accurately distinguishes between [ 18 F]FDG-PET-CT scans of lymphoma patients with and without hypermetabolic tumour sites. Deep learning might therefore be potentially useful to rule out the presence of metabolically active disease in such patients, or serve as a second reader or decision support tool., Funding: National Institutes of Health-National Cancer Institute Cancer Center Support Grant., Competing Interests: Declaration of interests MEM received honoraria for lectures from Siemens, General Electric, and Bristol Myers Squibb. GS received consulting fees from AbbVie, Beigene, Bristol-Myers Squibb Celgene, Epizyme, Genentech Roche, Genmab, Incyte, Janssen, Kite Gilead, Loxo, Milteniy, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Rapt, Takeda, and Ipsen; honoraria from AbbVie, Bayer, Incyte, Kite Gilead, Morphosys, Novartis, and Regeneron; participated on a Data Safety Monitoring Board or Advisory Board of Beigene; and has stock or stock options in Owkin. HH participated on Advisory Boards of Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, the Medical University of Vienna, and the Scientific Committee and Board of Trustees of the German Cancer Research Center; and is on the Board of Directors of Ion Beam Applications and Paige. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The protein expression of the prostate-specific membrane antigen correlates with unfavorable or aggressive histologic features of prostate cancer, resulting in use as a diagnostic PET imaging radiotracer and therapeutic target. Here, we discuss the methods to develop 225 Ac-DOTA-J591, an α-labeled compound targeting an extracellular epitope of prostate-specific membrane antigen, which is currently being studied in early clinical trials. In addition, we review quality control, radiation safety measures, and clinical considerations before administration of this radioimmunotherapeutic agent., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Radioactive iodine (RAI) is not routinely recommended for the adjuvant treatment of micropapillary thyroid carcinoma (MPTC). We aimed to report on clinical and pathologic factors associated with the use of RAI in these patients. We queried the Surveillance, Epidemiology, and End Results database for patients who underwent surgery for MPTC (tumor size ≤1 cm) from 1988 to 2009. We excluded patients without a biopsy-proven diagnosis, those diagnosed at autopsy, and patients with documented extra-thyroidal extension. Multivariate logistic regression models predicted the use of RAI based on patient, tumor, and treatment-related factors. We identified 24,076 patients with MPTC that were eligible for study inclusion. Of these, 6,172 (25.6%) received RAI. Lymph node metastases were present in 23.8 per cent of those for whom lymph node status was known. On multivariate analysis, an increasing number of positive nodes, increasing tumor size, Asian race, and male gender predicted the use of RAI. RAI use was less likely in those with advancing age, an increasing number of lymph nodes examined and patients that received less than a total thyroidectomy. Among node-negative patients, Asian race and increasing tumor size predicted the use of RAI. Factors predicting decreased use of RAI were an increasing number of lymph nodes examined, unknown race, less than a total thyroidectomy, and advancing age. A significant number of MPTC patients receive potentially unnecessary RAI. [ABSTRACT FROM AUTHOR]

Throughout the years, the role of nuclear medicine departments in the care of renal patients has changed as a result of technologic advancements and other factors. This study evaluated the current role of nuclear renal imaging.Methods: A survey was generated with questions about patient populations, the clinical indications most often seen, radiopharmaceutical use, measurement techniques, the average number of scans completed, and medical center/transplant team affiliations. The survey was sent to recipients on a mailing list acquired from the Nuclear Medicine Technology Certification Board.Results: Most of the responses came from departments in the southeastern United States. Most of the patient population is suburban. Nephrologists are the most common referring physicians for renal imaging. Most departments complete fewer than 10 renograms per month, and most departments use 99mTc-mercaptoacetyltriglycine as the radiopharmaceutical of choice. A camera-based measurement technique is used most often. Most departments report being affiliated with a medical center, but only about half of those medical centers perform renal transplantation. The most commonly seen clinical indication for renal imaging is renal obstruction, whereas the least commonly seen is urine leakage.Conclusion: These results provide a better understanding of the current role of nuclear medicine in the care of renal patients and how this role has changed over the years. [ABSTRACT FROM AUTHOR]

Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation. QUESTEL's ORBIT Intelligence system was used for the collection of technetium inventions disclosed in patents and patent applications in more than 96 countries in the period 2000-2022; 2768 patent documents were analyzed. Patent counting and analysis have shown that SPECT imaging using technetium-99m radiopharmaceuticals is still robust. The introduction of new technetium-99m radiopharmaceuticals into clinical routine goes beyond successful trials. In eastern economies, such as China and other emerging markets, patent applications are on the rise, while those in developed western countries are stagnating, with some exceptions for the United States. But despite the difficulties, academic and industrial research on these tracers remains essential for the development of nuclear medicine.

Background: Positron emission tomography (PET) is a diagnostic tool for lung cancer evaluation. No studies have ascertained practice patterns and determined the appropriateness of PET imaging in a large group of US patients with screen-detected lung nodules.Methods: We analyzed participants in the National Lung Screening Trial (NLST) with positive screening test results and identified individuals with a PET scan performed prior to lung cancer diagnosis (diagnostic PET). Appropriate scan was defined as one performed in a patient with a nodule ≥ 0.8 cm. Logistic regression was used to assess factors associated with diagnostic PET scan use and appropriateness of PET scan use.Results: Diagnostic PET imaging was performed in 1,556 of 14,195 patients (11%) with positive screen results; 331 of these (21%) were inappropriate. PET scan use by endemic fungal disease area was comparable although patients from the Northeast/Southeast were twice as likely as the West to have a diagnostic PET. Trial arm, older age, sex, nodule size ≥ 0.8 cm, upper lobe location, and spiculated margin were variables positively associated with use. Trial arm, older age, and spiculated margin were positively associated with appropriate use. Only 561 diagnostic PETs (36%) were recommended by a radiologist and 284 PETs performed for nodules < 0.8 cm (86%) were ordered despite no recommendation from a radiologist.Conclusions: PET imaging was differentially used in the NLST and inappropriately used in many cases against radiologist recommendations. These data suggest PET imaging may be overused in the lung cancer screening population and may contribute to excess health-care costs. [ABSTRACT FROM AUTHOR]

The concept of observation--going out and seeing what is happening in daily operations---would seem like a normal management activity, but the reality in practice of the philosophy and technique is often underutilized. Once an observation has been determined, the next steps are to test and validate any discoveries on paper. For process change to be implemented, numerical data is needed to back-up observations in order to be heard and taken seriously by the executive team. Boca Raton Regional Hospital saw an opportunity to improve the process for radiopharmaceutical standing orders within its nuclear imaging department. As a result of this observation, the facility realized improved savings and an increase in employee motivation. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma of the pancreas has a dismal prognosis. Surgical resection increases survival but is reliant on accurate detection and staging of disease. In overseas studies, 18 F-FDG positron emission tomography (PET) has been shown to have high diagnostic accuracy and staging utility, but local data remain sparse, in part because the technique has hitherto been unfunded via the Medicare benefits schedule. Although Commonwealth funding for rare tumours (including of the pancreas) has been recently approved to commence in late 2022, the proposed item descriptor wording implies that PET should lead to a significant change in management. Accordingly, the aims of this study are to characterize PET findings in newly diagnosed pancreatic adenocarcinoma using standard parameters, such as the SUV max , and assess the proportion of cases in which PET altered initial management planning., Methods: We analysed the PET findings of these cancers (presence and degree of metabolic activity in the primary lesion, as well as within malignant nodal and metastatic lesions) and compared the pre- and post-PET management plans of the referring specialists., Results: Of 51 patients we found that (a) increasing SUV max of the primary lesion correlated with an increase in disease stage (r-value = 0.335; P-value = 0.016), and (b) PET contributed to a significant change in management in 35% of patients., Conclusion: In newly diagnosed pancreatic adenocarcinoma, parameters in PET correlate with disease stage and the overall findings contribute to a significant management change in about 35% of patients., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Lung cancer is the leading cause of cancer death within the United States, yet prior studies have shown a lack of adherence to imaging and treatment guidelines in patients with lung cancer. This study evaluated the use of 18 F-FDG PET/CT imaging before subsequent radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC), as recommended by National Comprehensive Cancer Network guidelines, and whether the use of this imaging modality impacts cancer-specific survival. Methods: This was a retrospective study of the National Cancer Institute's Surveillance, Epidemiology, and End Results program of Medicare-linked data in patients with NSCLC. Hazard ratios and 95% CIs for overall and cancer-specific survival were estimated for patients diagnosed between 2006 and 2015 who underwent either 18 F-FDG PET/CT-based or CT-based imaging before subsequent RT. Results: Significant improvement in cancer-specific survival was found in patients who underwent 18 F-FDG PET/CT imaging before subsequent RT, compared with those who underwent CT (hazard ratio, 1.43 [95% CI, 1.32-1.55; P < 0.0001]). Although the National Comprehensive Cancer Network recommends 18 F-FDG PET/CT before subsequent RT, 43.6% of patients were imaged with CT alone. Conclusion: Many patients with NSCLC are not being imaged according to national guidelines before subsequent RT, and this omission is associated with a lower cancer-specific survival., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA׳s role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years. [ABSTRACT FROM AUTHOR]

The article reports on a study which identifies the differences in the approval status and regulatory actions for radiopharmaceuticals in the U.S. and Japan. The researchers have examined the similarities and differencies of the two regulatory systems since 1995. It suggests that international harmonization of the regulatory systems for manufactured novel drugs is important in the development of such drugs in other multinational countries.

The article discusses various issues related to the breasts and the advancements of molecular breast imaging (MBI). It describes the anatomy of the breast and examines the significance of breast composition. It tackles several genetic factors related to the risk of developing breast cancer, several conventional methods for breast imaging, and MBI. It offers information on the procedures and equipment for MBI and compares MBI with other breast imaging methods.

The article focuses on multiple myeloma, along with the medical diagnostic imaging examinations being used to diagnose the disease. Topics discussed include multiple myeloma's biological basis, its clinical features and diagnosis, and imaging and treatment protocols that are being implemented. Also mentioned are the origin of myeloma cells, the extra chromosome found in most myeloma cells, and research on novel biological agents that target or delay the growth of myeloma cells. INSET: International Staging System12.

The increased demand for medical diagnosis procedures has been recognized as one of the contributors to the rise of health care costs in the U.S. in the last few years. Nuclear medicine is a subspecialty of radiology that uses advanced technology and radiopharmaceuticals for the diagnosis and treatment of medical conditions. Procedures in nuclear medicine require the use of radiopharmaceuticals, are multi-step, and have to be performed under strict time window constraints. These characteristics make the scheduling of patients and resources in nuclear medicine challenging. In this work, we derive a stochastic online scheduling algorithm for patient and resource scheduling in nuclear medicine departments which take into account the time constraints imposed by the decay of the radiopharmaceuticals and the stochastic nature of the system when scheduling patients. We report on a computational study of the new methodology applied to a real clinic. We use both patient and clinic performance measures in our study. The results show that the new method schedules about 600 more patients per year on average than a scheduling policy that was used in practice by improving the way limited resources are managed at the clinic. The new methodology finds the best start time and resources to be used for each appointment. Furthermore, the new method decreases patient waiting time for an appointment by about two days on average. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia (SAB) causes considerable morbidity and mortality and requires comprehensive assessment for metastatic infection. The roles of routine imaging beyond echocardiography in SAB, including 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT), remain contentious. We performed a literature review of studies reporting impact of 18F-FDG-PET/CT on the clinical management or outcomes of SAB published through 1 March 2022. We identified 7 observational studies in which 18F-FDG-PET/CT frequently identified metastatic foci of infection, revealed foci undetected by prior investigations, led to additional source control procedures, and was associated with fewer infection relapses and lower mortality. Calculated numbers needed to treat for receipt of 18F-FDG-PET/CT were 7-9 to change antimicrobial therapy, 10-27 to lead to an additional source control procedure, and 4-8 to prevent death. These data are comparable to the evidence for clinical impact of other diagnostic modalities accepted as standard of care in SAB, and form a compelling basis for advocacy to expand access to 18F-FDG-PET/CT., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: The regulatory steps necessary to bring new PET radiopharmaceuticals to the clinic will be reviewed. The US Food and Drug Administration (FDA) provides approval to manufacture and use diagnostic radiopharmaceuticals, including those for cardiovascular PET/CT. Medicare not only provides insurance reimbursement for imaging procedures for its beneficiaries but also sets an example for third-party insurers to cover these procedures., Recent Findings: FDA provides extensive guidance for performing studies to obtain the safety and efficacy data needed to approve PET radiopharmaceuticals, and the pace of approval has recently increased. There also has been considerable progress in insurance coverage for PET by Medicare. Several promising agents for cardiovascular PET imaging are in the development pipeline. Challenges remain, however, including low levels of reimbursement and the application of appropriate use criteria for imaging procedures. It is important for cardiologists to understand the regulatory steps involved in translating PET radiopharmaceuticals to the clinic. Recent progress in both FDA approvals and Medicare coverage should facilitate the clinical use of new PET agents for molecular imaging of the heart., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

In recent years, there has been an influx of new tracers into the field of nuclear medicine and molecular imaging. Most of those that have been Food and Drug Administration-approved for clinical imaging exploit various mechanisms of protein biochemistry and molecular biology to bring about their actions, such as amino acid metabolism, protein folding, receptor-ligand interactions, and surface transport mechanisms. In this review, we attempt to paint a clear picture of the basic biochemistry and molecular biology of protein structure, translation, transcription, posttranslational modifications, and protein targeting, in the context of the various radiopharmaceuticals currently used clinically, all in an easy-to-understand language for entry-level technologists in the field. Tracer characteristics, including indications, dosage, injection-to-imaging time, and the logic behind the normal and pathophysiologic biodistribution of these newer molecular tracers, are also discussed., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The femur is the largest and strongest bone in the human body, and great force is necessary to fracture it. In adults, the most common cause of femur fracture is motor vehicle accidents. In children, abuse is often the cause. And in the elderly, femur fractures most often occur from falling. Radiography is the gold standard for diagnostic imaging of femurs, but diagnosis can be complicated with nondisplaced or occult fractures. Particularly in the emergency setting, modalities such as magnetic resonance imaging or computed tomography may be necessary. Effective treatment of femur fractures is needed to restore homeostatic function and prevent complications. [ABSTRACT FROM AUTHOR]

Recent advances in the development of new molecular imaging agents for PET have led to the approval of several new molecular entities for PET imaging by the U.S. Food and Drug Administration (FDA) within the last 10 y. However, the continued use of PET drugs for diagnostic imaging procedures is reliant on a sustainable network of PET manufacturing facilities operating in accordance with the regulations for current good manufacturing practices for PET drugs (title 21, Code of Federal Regulations, part 212). With this goal in mind, a public workshop entitled "PET Drugs: A Workshop on Inspections Management and Regulatory Considerations" was held on the FDA campus in Silver Spring, MD, on February 21, 2020. The workshop was cosponsored by the FDA's Center for Drug Evaluation and Research, the Society of Nuclear Medicine and Molecular Imaging, the Medical Imaging Technology Alliance, and the World Molecular Imaging Society, in collaboration with the Coalition of PET Drug Manufacturers. The organizing committee for the workshop consisted of representatives from academic and commercial PET manufacturers as well as FDA staff members. The coauthors on this paper are all members of the workshop-organizing committee., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The rise in demand for specialized medical services in the U.S. has been recognized as one of the contributors to increased health care costs. Nuclear medicine is a specialized service that uses relatively new technologies and radiopharmaceuticals with a short half-life for diagnosis and treatment of diseases. Nuclear medicine procedures are multi-step and have to be performed under restrictive time constraints. Consequently, managing patients in nuclear medicine clinics is a challenging problem that has received little research attention. In this paper, we derive algorithms for scheduling nuclear medicine patients and resources. We validate our algorithms using simulation of an actual nuclear medicine clinic based on historical data and compare the performance of our algorithms with the methods currently used in the clinic. The results we obtain provide useful insights into managing patients and resources in nuclear medicine clinics. For example, results show that patient throughput can be increased when some clinic resources are reserved to exclusively serve specific procedures on those days when higher demand is expected. [ABSTRACT FROM AUTHOR]

Many recent publications in nuclear medicine contain data on dosimetric findings for existing and new diagnostic and therapeutic agents. In many of these articles, however, a description of the methodology applied for dosimetry is lacking or important details are omitted. The intention of the EANM Dosimetry Committee is to guide the reader through a series of suggestions for reporting dosimetric approaches. The authors are aware of the large amount of data required to report the way a given clinical dosimetry procedure was implemented. Another aim of this guidance document is to provide comprehensive information for preparing and submitting publications and reports containing data on internal dosimetry. This guidance document also contains a checklist which could be useful for reviewers of manuscripts submitted to scientific journals or for grant applications. In addition, this document could be used to decide which data are useful for a documentation of dosimetry results in individual patient records. This may be of importance when the approval of a new radiopharmaceutical by official bodies such as EMA or FDA is envisaged. [ABSTRACT FROM AUTHOR]

Abstract: Ra-223 is a bone-seeking alpha emitter currently being evaluated as a radiopharmaceutical. Concurrent with the primary standardization, NIST established that calibration factors currently used for radionuclide calibrators in the clinical setting give readings 5.7–8.7% higher than the NIST calibrated activity. This work describes the determination of calibration factors specific to dose vials and syringes. Using the calibration factors derived with standard ampoules to measure syringe activities can give readings up to 3.6% too high. [Copyright &y& Elsevier]

Purpose: 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) is being developed for imaging cellular proliferation. The goals were to explore the capacity of FLT-positron emission tomography (PET) to distinguish between recurrence and radionecrosis in gliomas and compare the results to those obtained with 2-fluoro-2-deoxy-D: -glucose (FDG).Procedures: Fifteen patients with tumor recurrence and four with radionecrosis, determined by clinical course and magnetic resonance imaging results, were studied by dynamic [18F]FLT-PET with arterial blood sampling. A two-tissue compartment four-rate constant model was used to determine metabolic flux (K (FLT)), blood to tissue transport (K (1)), and phosphorylation (k (3)). FDG-PET scans were obtained 75-90 min postinjection.Results: K (FLT) and k (3), but not K (1) or k (3)/k (2) + k (3), reached significance for separating the recurrence from radionecrosis groups. Standardized uptake value and visual analyses of FLT or FDG images did not reach significance.Conclusions: K (FLT) (flux) appears to distinguish recurrence from radionecrosis better than other parameters, FLT and FDG semiquantitative approaches, or visual analysis of images of either tracer. [ABSTRACT FROM AUTHOR]

SummationCopper-64 (T1/2= 12.7 hours; β+, 0.653 MeV [17.8 %]; β−, 0.579 MeV [38.4 %]) has decay characteristics that allow for positron emission tomography (PET) imaging and targeted radiotherapy of cancer. The well-established coordination chemistry of copper allows for its reaction with a wide variety of chelator systems that can potentially be linked to peptides and other biologically relevant small molecules, antibodies, proteins, and nanoparticles. The 12.7-hours half-life of 64Cu provides the flexibility to image both smaller molecules and larger, slower clearing proteins and nanoparticles. In a practical sense, the radionuclide or the 64Cu-radiopharmaceuticals can be easily shipped for PET imaging studies at sites remote to the production facility. Due to the versatility of 64Cu, there has been an abundance of novel research in this area over the past 20 years, primarily in the area of PET imaging, but also for the targeted radiotherapy of cancer. The biologic activity of the hypoxia imaging agent, 60/64Cu-ATSM, has been described in great detail in animal models and in clinical PET studies. An investigational new drug application for 64Cu-ATSM was recently approved by the U.S. Food and Drug Administration (FDA) in the United States, paving the way for a multicenter trial to validate the utility of this agent, with the hopeful result being FDA approval for routine clinical use. This article discusses state-of-the-art cancer imaging with 64Cu radiopharmaceuticals, including 64Cu-ATSM for imaging hypoxia, 64Cu-labeled peptides for tumor-receptor targeting, 64Cu-labeled monoclonal antibodies for targeting tumor antigens, and 64Cu-labeled nanoparticles for cancer targeting. The emphasis of this article will be on the new scientific discoveries involving 64Cu radiopharmaceuticals, as well as the translation of these into human studies. [ABSTRACT FROM AUTHOR]

Abstract: Radiolysis is the process by which radioactively labeled compounds degrade. Many positron emission tomography (PET) radiopharmaceuticals produced with high radioactive concentrations and specific activities exhibit low radiochemical purity because of radiolysis. Little data exist that describe the radiolytic decomposition of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG). The objective of our study was to profile the degradation of [18F]FDG at various radioactive concentrations by measuring radiochemical purity at different time intervals and to study the effects of ethanol, a well-known reductant stabilizer of [18F]FDG preparations. [Copyright &y& Elsevier]

Background: This study estimates the length of time a patient might trigger security radiation detection devices after thallium 201 cardiac imaging. The US Department of Homeland Security is supporting the purchase and deployment of radiation detection pagers and portal monitors. Concurrently, there are an increasing number of cardiac perfusion imaging studies being performed using Tl-201. Therefore there is a higher probability that patients who have undergone nuclear medicine procedures could trigger alarms resulting in security questions.Methods and Results: The length of time patients could trigger such devices is estimated based on the radiopharmacokinetics of Tl-201 and potential radioactive contaminants as well as the capabilities of current sensitive radiation detection devices, assuming the radioactive sources are distributed in and attenuated by the patient. It is estimated that patients may trigger portable pager devices for up to 33 days and may trigger portal detectors for up to 51 days after studies using Tl-201. This is much longer than length of time for a patient to trigger such alarms after technetium 99m myocardial imaging tests, which is potentially up to 6 days.Conclusions: It should be standard practice for patients to be issued information cards that indicate the potential time for triggering security radiation detectors after diagnostic cardiac procedures involving the use of Tl-201 or other radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

As the result of a collaboration between the Detector and Imaging Group of Thomas Jefferson National Accelerator Facility (US), the Institute of Radioisotopes and Radiodiagnostic Products (IRRP) of N.C.S.R. "Demokritos" and the Biomedical Simulations and Imaging Applications Laboratory (BIOSIM) of National Technical University of Athens (Greece), a mouse sized camera optimized for Tc99m imaging was developed. The detector was built in Jefferson Lab and transferred to Greece, where it was evaluated with phantoms and small animals. The system will be used initially for planar dynamic studies in small animals, in order to assess the performance of new radiolabeled biomolecules for oncological studies. The active area of the detector is approximately 48 mm × 96 mm. It is based on two flat-panel Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMT), a pixelated NaI(Tl) scintillator and a high resolution lead parallel-hole collimator. The system was developed to optimize both sensitivity and resolution for in vivo imaging of small animals injected with technetium compounds. The results of system evaluation in planar mode with phantoms are reported. Results are presented for in vivo dynamic studies of mice injected with × 100 μCi of two conventional and novel radiopharmaceuticals, namely Tc99m -MDP and Tc99m -Bombesin. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that ejection fraction (EF) best predicts cardiovascular death but only measures of ischemia predict relative survival benefit from revascularization compared with medical therapy. Methods and Results: We followed up 5366 consecutive patients without prior revascularization who underwent stress electrocardiography-gated myocardial perfusion single photon emission computed tomography (MPS) for 2.8 ± 1.2 years, during which 146 cardiac deaths occurred (2.7%, 1.0%/y). The treatment received within 60 days after MPS was used to define the subgroups (revascularization in 402 patients, with cardiac death occurring in 6.2%, vs medical therapy in 4964 patients, with cardiac death occurring in 2.4%; P < .0001, χ2 = 18.7). Adjustment for nonrandomized treatment assignment used a propensity score based on logistic regression modeling of referral to revascularization. The percent of myocardium that was ischemic was the most important predictor of revascularization. The overall model (multivariate χ2 = 728, c index = 0.89, P < 10−5) was used as a propensity score. Cox proportional hazards analysis, assessing the relationship between MPS results, non-MPS covariates, and cardiac death, revealed that EF was superior to percent ischemic myocardium in the prediction of cardiac death after adjustment for pre-MPS data and the propensity score. However, an interaction between percent ischemic myocardium and revascularization was present such that, irrespective of EF, patients with little or no ischemia had an improved survival rate with medical therapy, whereas with increasing ischemia, progressive improvements in survival rate were noted with revascularization. Conclusions: Although EF predicts cardiac death, only inducible ischemia identifies which patients have a short-term benefit from revascularization. [Copyright &y& Elsevier]

An Office of Investigation (OI) investigation by the U.S. Nuclear Regulatory Commission (NRC) determined that, on three separate occasions over the past 10 years, technologists in one licensed nuclear medicine program were injected with radiopharmaceuticals without Authorized User knowledge or approval. The most recent instance, the one that precipitated the investigation, was discovered by the licensee and self-reported to the NRC; the other two instances were discovered during the OI investigation and came as a complete surprise to the licensee. In a mediated Alternative Dispute Resolution (ADR) involving the licensee, a professional, independent mediator and representatives of the NRC, an agreement was worked out whereby the licensee would admit to the violations and work with the NRC to inform other licensees that this is not an acceptable practice and that there are additional precautions that licensees can and should take to assure that such violations do not happen on their watch. [ABSTRACT FROM AUTHOR]

Background: Although single photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) have evolved considerably over the last decade, there is no recent comparison of diagnostic performance. This study was designed to assess relative image quality, interpretive confidence, and diagnostic accuracy by use of contemporary technology and protocols.Methods and Results: By consensus and without clinical information, 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated rest/pharmacologic stress studies in patient populations matched by gender, body mass index, and presence and extent of coronary disease. The patients were categorized as having a low likelihood for coronary artery disease (27 in each group) or had coronary angiography within 60 days. SPECT scans were acquired on a Cardio-60 system and PET scans on an ECAT ACCEL scanner. Image quality was excellent for 78% and 79% of rest and stress PET scans, respectively, versus 62% and 62% of respective SPECT scans (both p<.05). An equal percent of PET and SPECT gated images were rated excellent in quality. Interpretations were definitely normal or abnormal for 96% of PET scans versus 81% of SPECT scans (p=.001). Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70% (89% vs 79%, p=.03) and 50% (87% vs 71%, p=.003) and was higher in men and women, in obese and nonobese patients, and for correct identification of multivessel coronary artery disease.Conclusion: In a large population of matched pharmacologic stress patients, myocardial perfusion PET was superior to SPECT in image quality, interpretive certainty, and diagnostic accuracy. [ABSTRACT FROM AUTHOR]