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The main aim of this study was to evaluate the current state of bibliometric and altmetric research output of [ 225 Ac]Ac-Prostate specific membrane antigen (PSMA) and its implications for prostate cancer (PC). Both PubMed and Scopus digital libraries were systematically explored to retrieve relevant data on the topic of interest. The study of various bibliometric and altmetric indices was facilitated through the use of Microsoft Excel, Stata (Version 17.0), and VOSviewer (Version 1.6) Softwares. The parameters included in this study comprised the examination of published articles, annual trends, countries, institutions, authors, journals, and co-occurring keywords. From 2014 to 2024, our study examined a total of 100 publications within the given domain. The studies that received the highest citations primarily centered on the crucial topic of metastatic castration-resistant prostate cancer, with a particular emphasis on evaluating the safety and effectiveness of [ 225 Ac]Ac-PSMA therapy. Moreover, much scholarly inquiry has been devoted to examining the [ 225 Ac]Ac-PSMA adverse effects. Three high prolific countries (namely, Germany, United States, and South Africa) dominated the research render in terms of publications and citations. Finally, A strong correlation was observed between altmetric score and citation number (P < 0.001). The observed surge in scholarly research output and altmetric indicators associated with [ 225 Ac]Ac-PSMA signifies a shift in emphasis towards embracing alpha targeted therapy in PC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Molecular radiotherapy is the use of systemically administered unsealed radioactive sources to treat cancer. Theragnostics is the term used to describe paired radiopharmaceuticals localising to a specific target, one optimised for imaging, the other for therapy. For many decades, molecular radiotherapy has developed empirically. Standard administered activity schedules have been used without the prior estimation of the resulting tumour radiation absorbed dose by theragnostic imaging, or its subsequent measurement by serial scanning. This pragmatic approach has benefited many patients, however others who should have benefited have failed to do so as the radiation absorbed dose in the tumour was suboptimal. The accurate prediction and measurement of tumour and organ at risk radiation absorbed doses allows treatment to be personalised, and offers the prospect of improved clinical outcomes. To deliver this for all molecular radiotherapy patients would require not only a significant financial investment in equipment and skilled personnel, but also a change in attitude of those who believe that simple - or simplistic - schedules are easier to deliver, and that accurate dosimetry is too much trouble. Further clinical studies are required to demonstrate beyond doubt that the advantages of individualised treatment planning outweigh the inconvenience, and that the expense is justified by enhanced results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Multivisceral transplant (MVTx) refers to a composite graft from a cadaveric donor, which often includes the liver, the pancreaticoduodenal complex, and small intestine transplanted en bloc. It remains rare and is performed in specialist centres. Post-transplant complications are reported at a higher rate in multivisceral transplants because of the high levels of immunosuppression used to prevent rejection of the highly immunogenic intestine. In this study, we analyzed the clinical utility of 28 18 F-FDG PET/CT scans in 20 multivisceral transplant recipients in whom previous non-functional imaging was deemed clinically inconclusive. The results were compared with histopathological and clinical follow-up data. In our study, the accuracy of 18 F-FDG PET/CT was determined as 66.7%, where a final diagnosis was confirmed clinically or via pathology. Of the 28 scans, 24 scans (85.7%) directly affected patient management, of which 9 were related to starting of new treatments and 6 resulted in an ongoing treatment or planned surgery being stopped. This study demonstrates that 18 F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18 F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy.

This study was performed to determine if intra-arterial (i.a.) administration of 90 Y DOTATATE can provide an effective and safe alternative to the accepted standard for i.v. of peptide receptor radionuclide therapy (PRRT) in liver-dominant metastases of gastrointestinal pancreatic neuroendocrine neoplasm (GEP-NEN). A single site, prospective, preliminary case series study included 39 patients with histologically proven liver-dominant NEN. PRRT in the form of 1.15GBq 90 Y DOTATATE was given selectively into the liver via radiological catheterization of the hepatic artery, up to four times. The endpoint was radiological response (RECIST). Secondary endpoints assessed clinical well-being post-treatment, progression-free survival (PFS), overall survival (OS), and toxicity. Partial response (PR) was noted in 13% of subjects six weeks post-therapy, increasing to 24% at six months and dropping to 13% at 36 months. Disease progression (DP) was not seen at six weeks, was 5% at six months, and 47% at 36 months. Clinical response based on PS seen in 74% of patients at six weeks, 69% at six months, and 39% at 36 months had PFS and OS, respectively, of 22.7 months and 38.2 months. There was no difference in OS/PFS between those with RECIST PR and SD. One patient had significant toxicity (3%). Use of i.a. PRRT appears to be safe and effective in treating patients with liver-dominant NEN. In addition, the best OS (51 vs. 22 months) was seen when i.a. was used as an upfront treatment of bulky GEP-NEN liver metastases and not after i.v. 90 Y DOTATATE. The use of i.a. 90 Y DOTATATE PRRT appears to be safe and effective in treating patients with liver-dominant NEN.

The development of peptide receptor radionuclide therapy (PRRT) in disseminated neuroendocrine tumors (NETs) has been a long and protracted process. The idea was born within nuclear medicine academia but its translation to clinical practice has been marked by misunderstanding of the rigors of the processes used in drug registration. There were several false starts and some of the required basic science did not occur until after first in man studies. The standard process of preclinical, phase 1, 2 and 3 clinical trials were sometimes blurred and the required data including the assurances that patients were studied on protocol was missing from subsequent publications. Despite this there was a growing conviction and increasing evidence that the use of PRRT had a positive benefit in both survival and symptom relief in about 80% of treated patients. After a decade and a half of false starts and incomplete data a formal randomized controlled trial was conducted comparing PRRT with high dose somatostatin which clearly proved that PRRT was both safe, effective and the treatment of choice in hormone refractory NETs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim/objectives/background: The goal of therapy with unsealed radiopharmaceutical sources is to provide either cure or significant prolongation of disease-specific survival, and effective reduction and/or prevention of adverse disease-related symptoms or untoward events while minimizing treatment-associated side effects and complications. Radium-223 dichloride (radium-223) is an alpha particle-emitting isotope used for targeted bone therapy. This practice parameter is intended to guide appropriately trained and licensed physicians performing therapy with radium-223. Such therapy requires close cooperation and communication between the physicians who are responsible for the clinical management of the patient and those who administer radiopharmaceutical therapy and manage the attendant side effects. Adherence to this parameter should help to maximize the efficacious use of radium-223, maintain safe conditions, and ensure compliance with applicable regulations., Methods: This practice parameter was developed according to the process described on the American College of Radiology (ACR) website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the American College of Nuclear Medicine (ACNM), the American Society for Radiation Oncology (ASTRO), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). All these societies contributed to the development of the practice parameter and approved the final document., Results: This practice parameter addresses the many factors which contribute to appropriate, safe, and effective clinical use of radium-223. Topics addressed include qualifications and responsibilities of personnel, specifications of patient examination and treatment; documentation, radiation safety, quality control/improvement, infection control, and patient education., Conclusions: This practice parameter is intended as a tool to guide clinical use of radium-223 with the goal of facilitating safe and effective medical care based on current knowledge, available resources and patient needs. The sole purpose of this document is to assist practitioners in achieving this objective.

This guidance document is a brief consensus document covering the range and breadth of nuclear medicine practice in the UK, and identifies a few steps individual nuclear medicine practitioners and departments can take in the best interests of their patients. This guidance document should be used to inform local practice and does not replace local Trust policies or any relevant legislation. At all times, the best interests of the patients should be paramount. Please read this guidance in conjunction with previous editorial (COVID-19- Nuclear Medicine Departments, be prepared! by Huang HL, Allie R, Gnanasegaran G, Bomanji. J Nucl Med Commun 2020; 41:297-299). Although some aspects of this guidance are time-sensitive due to the nature of the global emergency, we believe that there is still sufficient information to provide some key guiding principles.

Objectives: This study determined whether in vivo positron emission tomography (PET) of arterial inflammation ( 18 F-fluorodeoxyglucose [ 18 F-FDG]) or microcalcification ( 18 F-sodium fluoride [ 18 F-NaF]) could predict restenosis following PTA., Background: Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty., Methods: In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18 F-FDG and 18 F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months., Results: Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation ( 18 F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification ( 18 F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both 18 F-FDG (cut-off TBR max value of 1.98) and 18 F-NaF (cut-off TBR max value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001)., Conclusions: Baseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neuroendocrine neoplasms of the pancreas (p-NEN) are common gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). The aim of this retrospective study was to review the of value of Somatostatin Receptor Scintigraphy (SRS) in initial detection of p-NEN, evaluation of tumour extent and as imaging follow-up after radical surgery in patients with confirmed well (NETG1) or moderate (NETG2) differentiated p-NEN based on pathological WHO 2017 classification., Material and Methods: Overall 281 patients with confirmed p-NEN were enrolled. The SRS was performed to evaluation of primary p-NEN, also to assess clinical stage of disease, based on current World Health Organization (WHO) classification and during clinical follow-up. A total of 829 examinations were performed over time in these 281 patients using 99mTc HYNICTOC. Images were acquired between 1 - 3 h after i.v. injection of radiotracer. Initially whole body WB-SPECT and then WB-SPECT/CT, with standard iterative reconstruction were used., Results: There were 159 patients with NETG1 (57%) and 122 subjects with NETG2 (43%). The female to male ratio was 1.1:1. In 68 patients (22%) with NETG1/G2 eight-seven SRS (10%) were performed to confirm initial diagnosis. SRS results were as follow: true positive (TP) = 84 (97%), false negative (FN) = 3 (3%), no true negative (TN) or false positive (FP) results of SRS examination (sensitivity of SRS per patient was 96%). In 198 subjects (66%) SRS was used in evaluation and re-evaluation of the clinical stage, A total of 661 (80%) examinations were carried out in these patients. There were TP=514 (77%), TN=136 (21%), FN=7 (1%) and FP=4 (1%) results. The sensitivity and specificity per patient were: 96% and 95%. The sensitivity and specificity per study: 98% and 97%. In 35 patients (12%) SRS was used as imaging follow-up after radical surgery, there were overall 81 examination (10%) which were performed. There were 76 (91%) TN results of examinations of SRS and in 4 patients we identified recurrence (TP). In total, which consists of initial diagnosis/staging and follow-up patients, the sensitivity of SRS was 96% and specificity 97% per patient and per study sensitivity and specificity was 98%., Conclusions: SRS using 99mTc HYNICTOC acquired in WB-SPECT or WB-SPECT/CT techniques is an excellent imaging modality in detection of primary NETG1/G2 p-NEN. Our study confirms that SRS has high sensitivity and specificity, as a result has tremendous value as an examination method to assess clinical stage of disease and as an imaging follow-up after radical treatment.

Radioimmunotherapy (RIT) has been available for some time to treat patients with non-Hodgkin's lymphoma, but its use in Hodgkin's lymphoma has been less available, partly because of the need to find an appropriate antibody. A new radioiodinated chimeric antibody directed against the CD25 epitope ( 131 I basiliximab) seems promising, but assessment of response has been difficult. 18 F-fluorodeoxyglucose-positron emission tomography ( 18 F-FDG-PET) has become a standard method by which the response of Hodgkin's disease to chemotherapy is both predicted and assessed with well-understood criteria of response. The aim of this study is to determine 18 F-FDG-PET can be used to assess response to RIT. Pre- and post-treatment 18 F-FDG-PET imaging was performed in a series of 13 patients with advanced Hodgkin's disease who had failed conventional therapy and had been enrolled on a compassionate use program for treatment with 131 I basiliximab. The 131 I basiliximab was given at an activity of 1200MBq/m 2 with one patient receiving 2 cycles and the rest a single cycle. The 18 F-FDG-PET studies were compared using the "Deauville" criteria and by comparing the maximum standardized uptake value (SUVmax) of target tumors before and 4 and 8 weeks after treatment. All patients survived long enough for their initial 18 F-FDG-PET-computed tomography scan at 4 weeks after their 131 I basiliximab therapy. One out of ten patients with "Deauville" Grade 4 or 5 response died during the 6-month follow-up period. Two out of three patients with a "Deauville" Grade 2 or 3 response died in the follow-up period. The mean SUVmax pretreatment was 11.9 (±4.7); at 4-week posttreatment, the mean SUVmax was significantly lower at 6.5 (±5.8) ( P = 0.02). At 8 weeks, the mean SUVmax was 8.8 (±7.0), which was not significantly different from the pretreatment level. 18 F-FDG-PET imaging is able to predict the short-term response to treatment of Hodgkin's disease by RIT, and an initial poor response appears to predict poor outcome. Early changes in 18 F-FDG-PET uptake did not predict sustained response and by 8 weeks all but one patient had recurrent disease., Competing Interests: There are no conflicts of interest.

Neuroendocrine tumors (NETs) are a diverse group of tumors that often present late due to nonspecific symptoms. These tumors frequently express somatostatin receptors (SSRs), which allows for positron emission tomography/computed tomography (PET/CT) imaging with Ga-68-DOTATATE. In eligible patients, this may then be followed by peptide receptor radionuclide therapy (PRRT). Here, we report our initial results and experience with PRRT in a developing country, as one of the first groups to provide this therapy in South Africa. Eligible patients with confirmed inoperable NETs were recruited prospectively and treated with Lu-177-DOTATATE. Baseline imaging was performed with either single-photon emission CT- or PET-based SSR analogs, whereas follow-up was performed with 68 Ga-DOTATATE PET/CT 6 months post treatment completion. Interim treatment response evaluation was based on post therapy imaging of Lu-177-DOTATATE. A total of 48 patients with a mean age of 58 years were treated with PRRT, of whom 22 (46%) demonstrated stable disease, 20 (42%) demonstrated a partial response, and 6 (12%) demonstrated progressive disease. The median progression-free survival (PFS) was 20 months with an interquartile range (IQR) 25%-75% of 4.5-30 months. The median freedom from progression duration was 32 months with an IQR 25%-75% of 25-40 months, and the median overall survival was 10 months with an (IQR) 25%-75% of 5-24 months. Our subgroup analysis demonstrated an inverse association between metabolic tumor volume with PFS, which requires further validation. In conclusion, PRRT with Lu-177-DOTATATE resulted in a median PFS of 20 months in patients with inoperable NETs in the absence of significant side effects., Competing Interests: There are no conflicts of interest.

Sarcoidosis is a systemic disease of unknown aetiology characterised by the formation of noncaseating granulomas in various organs and tissues. The various imaging modalities that are useful in the investigation of lesions, staging and establishing indications for treatment include: conventional radiography, CT, MRI, and scintigraphy with ⁶⁷Ga, ²⁰¹Tl, 99mTc sestamibi, and somatostatin receptor scintigraphy (SRS) as well as ¹⁸F-FDG-PET/CT. This paper discusses the most commonly used technique of the scintigraphic, gallium (⁶⁷Ga) citrate) and its role in the evaluation and monitoring of patients with sarcoidosis.

Cerebrovascular disease encompasses a range of pathologies that affect different components of the cerebral vasculature and brain parenchyma. Large artery atherosclerosis, acute cerebral ischaemia, and intracerebral small vessel disease all demonstrate altered metabolic processes that are key to their pathogenesis. Although structural imaging techniques such as MRI are the mainstay of clinical care and research in cerebrovascular disease, they have limited ability to detect these pathophysiological processes in vivo. By contrast, PET can detect and quantify metabolic processes that are relevant to each facet of cerebrovascular disease. Information obtained from PET studies has helped to shape the understanding of key concepts in cerebrovascular medicine, including vulnerable atherosclerotic plaque, salvageable ischaemic penumbra, neuroinflammation and selective neuronal loss after ischaemic insult. PET has also helped to elucidate the relationships between chronic hypoxia, neuroinflammation, and amyloid-β deposition in cerebral small vessel disease. This Review describes how PET-based imaging of metabolic processes at the neurovascular interface has contributed to our understanding of cerebrovascular disease.

Objective: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period., Design: Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed., Results: Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 ( YY1 ) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden., Conclusion: Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease., (© 2017 The authors.)

Primary and secondary liver malignancies are common and associated with a poor prognosis. Surgical resection is the treatment of choice; however, many patients have unresectable disease. In these cases, several liver directed therapies are available, including selective internal radiation therapy (SIRT). SIRT is a multidisciplinary treatment involving nuclear medicine, interventional radiology and oncology. High doses of localised internal radiation are selectively delivered to liver tumour tissues, with relative sparing of adjacent normal liver parenchyma. Side effects are minimal and radiation protection measures following treatment are straightforward. In patients who have progressed following chemotherapy, clinical trials demonstrate prolonged liver progression-free survival. SIRT is offered at 10 centres in England via the NHS England Commissioning through Evaluation programme and is approved by the National Institute for Health and Care Excellence for certain liver malignancies. SIRT holds unique promise for personalised treatment of liver tumours., (© Royal College of Physicians 2017. All rights reserved.)

Background: Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([ 18 F]FDG PET), [ 18 F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover., Objectives: This study tested the efficacy of gallium-68-labeled DOTATATE ( 68 Ga-DOTATATE), a somatostatin receptor subtype-2 (SST 2 )-binding PET tracer, for imaging atherosclerotic inflammation., Methods: We confirmed 68 Ga-DOTATATE binding in macrophages and excised carotid plaques. 68 Ga-DOTATATE PET imaging was compared to [ 18 F]FDG PET imaging in 42 patients with atherosclerosis., Results: Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68 Ga-DOTATATE ligand binding to SST 2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68 Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68 Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBR max ) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68 Ga-DOTATATE mTBR max predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [ 18 F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [ 18 F]FDG mTBR max differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [ 18 F]FDG spillover rendered coronary [ 18 F]FDG scans uninterpretable in 27 patients (64%). Coronary 68 Ga-DOTATATE PET scans were readable in all patients., Conclusions: We validated 68 Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68 Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [ 18 F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal 'incidentalomas' detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing's syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11 C-metomidate PET-CT in primary aldosteronism., Competing Interests: The authors declare no conflict of interest.

Background: Abdominal aortic aneurysm (AAA) wall inflammation and mechanical structural stress may influence AAA expansion and lead to rupture. We hypothesized a positive correlation between structural stress and fluorine-18-labeled 2-deoxy-2-fluoro-d-glucose ( 18 F-FDG) positron emission tomography-defined inflammation. We also explored the influence of computed tomography-derived aneurysm morphology and composition, including intraluminal thrombus, on both variables., Methods and Results: Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent 18 F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm 18 F-FDG standardized uptake value within aortic wall and wall structural stress, patient clinical characteristics, aneurysm morphology, and compositions was explored using a hierarchical linear mixed-effects model. On univariate analysis, local aneurysm diameter, thrombus burden, extent of calcification, and structural stress were all associated with 18 F-FDG uptake (P<0.05). AAA structural stress correlated with 18 F-FDG maximum standardized uptake value (slope estimate, 0.552; P<0.0001). Multivariate linear mixed-effects analysis revealed an important interaction between structural stress and intraluminal thrombus in relation to maximum standardized uptake value (fixed effect coefficient, 1.68 [SE, 0.10]; P<0.0001). Compared with other factors, structural stress was the best predictor of inflammation (receiver-operating characteristic curve area under the curve =0.59), with higher accuracy seen in regions with high thrombus burden (area under the curve =0.80). Regions with both high thrombus burden and high structural stress had higher 18 F-FDG maximum standardized uptake value compared with regions with high thrombus burdens but low stress (median [interquartile range], 1.93 [1.60-2.14] versus 1.14 [0.90-1.53]; P<0.0001)., Conclusions: Increased aortic wall inflammation, demonstrated by 18 F-FDG positron emission tomography, was observed in AAA regions with thick intraluminal thrombus subjected to high mechanical stress, suggesting a potential mechanistic link underlying aneurysm inflammation., (© 2016 The Authors.)

Aim: To determine the efficacy of (90)Y [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) in 67 patients with pancreatic and small bowel neuroendocrine tumors (NETs)., Patients & Methods: The primary efficacy end point was overall survival (OS) and secondary end points were progression-free survival (PFS) and tumor response., Results: Median PFS in pancreatic and small bowel NETs was 25 and 28 months, respectively, and median OS was 42 and 38.5 months, respectively. No intergroup differences in median OS (p = 0.945) or PFS (p = 0.174) were found, also after adjustment for tumor origin, secretory status and grade, and patient's gender., Conclusion: (90)Y-DOTATATE may have similar efficacy in pancreatic and small bowel NETs. Better WHO performance status at baseline seems to be associated with more favorable outcomes.

To assess the added value of single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with end-stage renal failure (ESRF) or renal transplant recipients in whom focal infection was suspected. Gallium-67 (Ga-67) citrate scintigrams of 18 patients (10 in ESRF and eight with renal transplants) were reviewed. Sites of abnormal uptake seen on the whole body and SPECT were noted. A SPECT/CT was also reviewed to see if additional information could be obtained. Imaging results were compared with the final diagnosis. Overall, 14 out of 18 (78%) patients had a proven cause to explain symptoms while four patients did not have a final cause identified. Infection was proven in the final diagnosis in 12 out of 14 (86%) patients. Of the 10 patients with ESRF, six had confirmed infection with the Ga-67 citrate study correctly identifying five out of six (83%) patients, and SPECT/CT providing additional information in four out of five (80%) patients. In the eight renal transplant recipients, six had a confirmed source of infection (all identified by the Ga-67 citrate study). SPECT/CT provided additional information in two out of six (33%) patients. Ga-67 citrate imaging had an overall sensitivity of 13/14 (93%), with one false negative. SPECT/CT provided an additional contribution in eight out of 18 (44%) patients by better defining the location/extent of infection and differentiating the physiological from the pathological uptake.

Positron emission tomography (PET) has become widely established in oncology. Subsequently, a whole new “toolbox” of tracers have become available to look at different aspects of cancer cell function and dysfunction, including cell protein production, DNA synthesis, hypoxia and angiogenesis. In the past 5 years, these tools have been used increasingly to look at the other great killer of the developed world: cardiovascular disease. For example, inflammation of the unstable plaque can be imaged with 18-fludeoxyglucose (18F-FDG), and this uptake can be quantified to show the effect that statins have in reducing inflammation and explains how these drugs can reduce the risk of stroke. 18F-FDG has also become established in diagnosing and monitoring large-vessel vasculitis and has now entered routine practice. Other agents such as gallium-68 (68Ga) octreotide have been shown to identify vascular inflammation possibly more specifically than 18FFDG.Hypoxia within the plaque can be imaged with 18F-fluoromisonidazole and resulting angiogenesis with 18F-RGD peptides. Active calcification such as that found in unstable atheromatous plaques can be imaged with 18F-NaF. PET imaging enables us to understand the mechanisms by which cardiovascular disease, including atheroma, leads tomorbidity and death and thus increases the chance of finding new and effective treatments.

Aims: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers., Methods: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis., Results: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively)., Conclusion: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Radiosynovectomy is a safe and repeatable treatment method of chronic synovitis with synovial overgrowth and refractory chronic or acute inflammatory joint effusion. It consist in the intraarticular administration of a radioactive isotope in the form of a colloid causing the extinguishing of active synovitis. The radiocolloid causes permanent irradiation of the synovium with beta ray electron beams, which ultimately leads to its fibrosis and extinguishes the inflammatory process destroying the joint. The main indications for radiosynovectomy include chronic and acute arthritis in the course of systemic diseases, intraarticular bleeding in hemorrhagic diatheses (hemophilia), selected cases of osteoarthritis, recurrent effusions following surgery, e.g. arthroplasty, or other iatrogenic post-surgery complications causing arthritis. Radiosynovectomy is also performed in pigmented villonodular synovitis and crystal synovitis. The most common method used to determine the eligibility for radiosynovectomy is an ultrasound, which shows the location and activity of the thickened synovium. The administration of a radiocolloid into the joint, sheath or bursa should also be performed under the control of the ultrasound image, as this ensures a precise location of the puncture needle and full control of the isotope administration process. Clinical efficacy of radiosynovectomy depends on the proper qualification of patients for the procedure. The success rate of radiosynovectomy in common indications is 65-80%. It is confirmed by the visualization of avascular (fibrotic) synovium in follow-up ultrasound tests. The aim of this article is to present techniques and indications for the radiosynovectomy treatment.

Background: The aim of this initial study was to evaluate the clinical and radiological effectiveness of radioembolization (RE) using 188Re-Human Serum Albumin (HSA) microspheres in patients with advanced, progressive, unresectable primary or secondary liver cancers, not suitable to any other form of therapy., Material/methods: Overall, we included 13 patients with 20 therapy sessions. Clinical and radiological responses were assessed at 6 weeks after therapy, and then every 3 months. The objective radiological response was classified according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 by sequential MRI. Adverse events were evaluated using NCI CTCAE v.4.03., Results: There were 4 patients with hepatocellular carcinoma (HCC), 6 with metastatic colorectal cancer (mCRC), 2 with neuroendocrine carcinoma (NEC), and 1 patient with ovarian carcinoma. Mean administered activity of 188Re HSA was 7.24 GBq (range 3.8-12.4) A high microspheres labeling efficacy of over 97±2.1% and low urinary excretion of 188Re (6.5±2.3%) during first 48-h follow-up. Median overall survival (OS) for all patients was 7.1 months (CI 6.2-13.3) and progression-free survival (PFS) was 5.1 months (CI 2.4-9.9). In those patients who had a clinical partial response (PR), stable disease (SD), and disease progression (DP) as assessed 6 weeks after therapy, the median OS was 9/5/4 months, respectively, and PFS was 5/2/0 months, respectively. The treatment adverse events (toxicity) were at an acceptable level. Initially and after 6 weeks, the CTC AE was grade 2, while after 3 months it increased to grade 3 in 4 subjects. This effect was mostly related to rapid cancer progression in this patient subgroup., Conclusions: The results of this preliminary study indicate that RE using 188Re HSA is feasible and a viable option for palliative therapy in patients with extensive progressive liver cancer. It was well tolerated by most patients, with a low level of toxicity during the 3 months of follow-up.

This review focuses on the current evidence available on the use of single-photon emission computed tomography-computed tomography (SPECT-CT) in infection imaging. The single-photon functional agents commonly used to image infection include In-111-labelled or Tc-99m-labelled leucocytes, Ga-67 citrate, Tc-99m-biphosphonates and radiolabelled antigranulocyte antibodies. Although many of these agents have been available for a long time, the development of hybrid SPECT-CT technology has led to a wider use of these agents. This review shows that the application of CT to single-photon imaging techniques for imaging infection can significantly improve the accuracy of the technique by increasing the specificity and better defining the location and extent of suspected disease. Hybrid fusion images also increase the confidence of the individual in reporting and seem to be applicable to a wide range of clinical situations. We believe that, overall, SPECT-CT, by providing a clearer assessment of whether infection is present and an accurate localization of the disease so that optimum treatment can be initiated, has a role in infection imaging.

Introduction and Background: Positron emission tomography (PET) has started to develop beyond its roots in glucose imaging, expanding to study other parameters of the tumour and its microenvironment., Sources of Data: A review of imaging literature over the past 5 years has shown that functional imaging with PET is starting to exploit our increasing knowledge of genomics and the phenotypic expression of cells and how they interact with their microenvironment., Areas of Agreement: For most of those working in this field, there is agreement that therapeutic outcomes for patients can only be obtained by the assessment and continued reassessment not only of the tumour microenvironment, but also how it is changed by treatment., Areas of Controversy: Although PET offers a tool by which the tumour and its microenvironment can be assessed in vivo without the need for multiple interventions, the cost of PET is high and there is a cumulative radiation burden with repeated studies. As the quantity and quality of PET scans increase, we are able to assess tumour cell turn over, metabolism, hypoxia, angiogenesis and a variety of other factors that might affect tumour survival and response to treatment., Areas Timely for Developing Research: As it is impossible to do everything for every patient, we need to know what are the critical factors in the tumour cell microenvironment in each patient and need to have the tools to assess that factor.

Objectives: To assess whether an association exists between drainage to multiple basins and lymphatic metastasis in patients with truncal melanoma., Methods: We retrospectively reviewed 227 patients with primary malignant melanoma between January 2006 and December 2009. All patients received an intradermal injection of (99m)Tc-nanocolloid and lymphoscintigraphy followed by sentinel node biopsy. Pre-staging histology with Breslow thickness from excision biopsy was also obtained., Results: 82/227 (36%) patients with primary truncal melanoma were identified. Nodal histology was positive for metastatic disease in 27/82 (32.9%) patients. Of these 27, 15 had 1 basin of drainage, 7 had 2 basins of drainage and 5 had 3 basins of drainage. Of the 55 node-negative patients, 35 had 1 basin, 18 had 2 basins and 2 had 3 basins of drainage. We found no significant correlation with sentinel node positivity and those that had ≥2 drainage basins. Breslow thickness was available in 65/82(79.2%) patients. Sentinel node biopsy was positive in 6/28 patients who had <1.5 mm thickness, 8/14 who had a 1.5-3.9 mm thickness and 9/23 who had ≥4 mm thickness. There was a significant correlation between Breslow thickness of ≥4 mm and nodal positivity (P = 0.03)., Conclusion: This study demonstrates no association between multiple drainage basins and sentinel node histology. Sentinel lymph node status did correlate with Breslow thickness.

Aim: The goal of the study is to correlate serum calcium levels with the results of dual-phase (99m)Tc-sestamibi parathyroid scintigraphy to find the best cut-off level of the serum calcium that correlates with a positive presurgery., Methods: In 111 patients, serum calcium and plasma parathormone (PTH) levels were compared with the results of the (99m)Tc-MIBI scintigraphy and with this data determined the level of calcium above which the (99m)Tc-MIBI scintigraphy was likely to be positive and below which the study was likely to be negative., Results: In total, 11 men (18%) and 50 women (82%) had a positive (99m)Tc-MIBI study. Overall 67% of those patients with a positive (99m)Tc-MIBI study had a PTH >200 ng l(-1) compared to only 9% of those with a negative (99m)Tc-MIBI scintigraphy; however, for those with a positive study on an early (99m)Tc-MIBI scintigraphy, this rose to 85%. Overall a serum calcium of >2·70 mmol l(-1) was found in 82% of patients with a positive (99m)Tc-MIBI study but only 14% of those with a negative (99m)Tc-MIBI study, this is rose to 97% of patients with a parathyroid adenoma identified on early images. It is also shown that patients whose serum total calcium <2·51 mmol l(-1) rarely have positive (99m)Tc-MIBI scintigraphy., Conclusion: (99m)Tc-MIBI parathyroid scintigraphy is most likely to yield identification and localization of a parathyroid adenoma when both PTH and calcium are elevated; however, although there is no lower limit of PTH which can predict a negative study, we cannot recommend (99m)Tc-MIBI parathyroid scintigraphy if the serum calcium is <2·51 mmol l(-1)., (© 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Purpose: The aim of this analysis was to evaluate the response to standard activity of (131)I-meta-iodobenzylguanidine (MIBG) in patients with disseminated neuroendocrine tumours (NETs), comparing overall survival of patients with symptomatic response, tumour size (as assessed by CT) and relevant plasma tumour markers., Methods: A retrospective review of patients who had undergone (131)I-MIBG treatment between March 2001 and December 2006 was carried out. The administered activity of (131)I-MIBG was 5.5 GBq (NETs) and 7 GBq (phaeochromocytoma). Three cycles of treatment were planned with an interval of 10-12 weeks. A pre-therapy scan with (123)I-MIBG was performed to ascertain appropriate biodistribution., Results: Thirty-eight patients were identified. Only two patients developed significant bone marrow suppression. Symptomatic response: data were available in 37 of 38 patients: 15 patients had improved symptoms, 19 had no improvement in symptoms and 3 were asymptomatic. In those with a symptomatic response, the median overall survival was 58 months vs no response of 20.0 months (p = 0.001). CT response: in those with stable disease, the median overall survival was 58 months compared with progressive disease of 16.0 months. The difference between these groups was significant (p = 0.006). Hormonal response: this was available in only 20 of 38 patients. The median overall survival was the same for patients that had increased hormone levels and patients that had stable/decreased hormone levels (48 months)., Conclusion: Standard activity (131)I-MIBG is well tolerated. Symptomatic response to treatment is a significant predictor of overall survival. Whilst CT response also appears to predict survival, hormonal levels do not appear to correlate with survival.

Background: To evaluate the clinical and radiological effectiveness of [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) Y-90 in patients with extensive progressive gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs)., Materials and Methods: Sixty patients with histologically proven GEP-NETs were treated with DOTATATE Y-90. Clinical responses were assessed 6 weeks after completing therapy and then after each of the 3- to 6-month intervals. The radiological response was classified according to RECIST criteria., Results: At 6 months after final treatment, radiological partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was observed in 13 patients (23%), and the remaining patients had stable disease (SD; less than 30% decrease in the sum of the longest diameter of target lesions or less than 20% increase in the sum of the longest diameter of target lesions) (77%). Clinical PR at 6 months was in 43 patients (72%), nine patients had SD and progressive disease (PD) was noted in eight patients. Median progression-free survival (PFS) was 17 months, while the median overall survival (OS) was 22 months. In eight patients with early PD, the PFS was 4.5 and OS 9.5 months, while in those with SD or PR, PFS and OS were 19.5 and 23.5 months, respectively. After 12 months of follow-up, five patients had World Health Organization (WHO) grade 2 or 3 renal toxicity. Haematological toxicity (WHO grade 3 and 4) was noted during therapy in 10% of patients and persisted in 5%., Conclusions: DOTATATE Y-90 therapy is effective and relatively safe in patients with GEP-NET. Standard doses of DOTATATE Y-90 result in a relatively low risk of myelotoxicity. However, due to ongoing risk of renal toxicity, careful monitoring of the kidney is recommended.