ABSTRACT
The main aim of this study was to evaluate the current state of bibliometric and altmetric research output of [225Ac]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 [225Ac]Ac-PSMA therapy. Moreover, much scholarly inquiry has been devoted to examining the [225Ac]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 [225Ac]Ac-PSMA signifies a shift in emphasis towards embracing alpha targeted therapy in PC.
Subject(s)
Bibliometrics , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/radiotherapy , Glutamate Carboxypeptidase II/metabolism , Antigens, Surface/metabolismABSTRACT
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.
Subject(s)
Neoplasms , Radiometry , Humans , Radiotherapy Dosage , Radiometry/methods , Radiation Dosage , Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Radiopharmaceuticals/therapeutic use , RadiotherapyABSTRACT
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 18F-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 18F-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 18F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy.
ABSTRACT
This study was performed to determine if intra-arterial (i.a.) administration of 90Y 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 90Y 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. 90Y DOTATATE. The use of i.a. 90Y DOTATATE PRRT appears to be safe and effective in treating patients with liver-dominant NEN.
ABSTRACT
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.
Subject(s)
Evidence-Based Medicine , Radiotherapy/methods , Receptors, Peptide/metabolism , Humans , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/radiotherapyABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Radium/therapeutic use , Combined Modality Therapy , Humans , Radioisotopes/therapeutic useABSTRACT
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.
Subject(s)
Coronavirus Infections/diagnosis , Nuclear Medicine , Pneumonia, Viral/diagnosis , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Diagnostic Imaging , Hand Hygiene , Hospital Departments , Humans , National Health Programs , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Radiopharmaceuticals/therapeutic use , United KingdomABSTRACT
OBJECTIVES: This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-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 18F-FDG and 18F-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 (18F-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 (18F-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 18F-FDG (cut-off TBRmax value of 1.98) and 18F-NaF (cut-off TBRmax 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.
Subject(s)
Angioplasty, Balloon/adverse effects , Femoral Artery/diagnostic imaging , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/therapy , Positron-Emission Tomography , Aged , Aged, 80 and over , Female , Femoral Artery/physiopathology , Fluorodeoxyglucose F18/administration & dosage , Humans , Male , Middle Aged , Peripheral Arterial Disease/physiopathology , Plaque, Atherosclerotic , Predictive Value of Tests , Prospective Studies , Radiopharmaceuticals/administration & dosage , Recurrence , Risk Factors , Sodium Fluoride/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/metabolism , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/metabolism , Receptors, Somatostatin/metabolism , Single Photon Emission Computed Tomography Computed Tomography , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Retrospective Studies , Young AdultABSTRACT
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 (131I basiliximab) seems promising, but assessment of response has been difficult. 18F-fluorodeoxyglucose-positron emission tomography (18F-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 18F-FDG-PET can be used to assess response to RIT. Pre- and post-treatment 18F-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 131I basiliximab. The 131I basiliximab was given at an activity of 1200MBq/m2 with one patient receiving 2 cycles and the rest a single cycle. The 18F-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 18F-FDG-PET-computed tomography scan at 4 weeks after their 131I 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. 18F-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 18F-FDG-PET uptake did not predict sustained response and by 8 weeks all but one patient had recurrent disease.
ABSTRACT
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 68Ga-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 IQR25%-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.
ABSTRACT
This corrects the article DOI: 10.1038/nrneurol.2017.129.
ABSTRACT
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, ²°¹Tl, 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.
Subject(s)
Gallium Radioisotopes , Radionuclide Imaging/methods , Sarcoidosis/diagnostic imaging , Humans , Organ SpecificityABSTRACT
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.
Subject(s)
Brachytherapy , Liver Neoplasms/radiotherapy , England , Humans , State MedicineABSTRACT
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-ß 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.
Subject(s)
Cerebrovascular Circulation , Cerebrovascular Disorders/diagnostic imaging , Neuroimaging/methods , Positron-Emission Tomography/methods , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Calcinosis/diagnostic imaging , Cerebral Amyloid Angiopathy/diagnostic imaging , Cerebral Amyloid Angiopathy/pathology , Humans , Hypoxia, Brain/diagnostic imaging , Inflammation , Magnetic Resonance Imaging , Plaque, Atherosclerotic/diagnostic imaging , Radioactive Tracers , Rupture, SpontaneousABSTRACT
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 177Lu-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.
ABSTRACT
BACKGROUND: Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. OBJECTIVES: This study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. METHODS: We confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis. RESULTS: Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) 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). 68Ga-DOTATATE mTBRmax 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 [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax 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 [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients. CONCLUSIONS: We validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).
Subject(s)
Atherosclerosis/diagnostic imaging , Fluorodeoxyglucose F18 , Inflammation/diagnostic imaging , Organometallic Compounds , Positron Emission Tomography Computed Tomography , Aged , Carotid Arteries/diagnostic imaging , Coronary Vessels/diagnostic imaging , Female , Humans , Macrophages/metabolism , Male , Middle Aged , Receptors, Somatostatin/analysis , Receptors, Somatostatin/metabolismABSTRACT
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 (18F-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 18F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm 18F-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 18F-FDG uptake (P<0.05). AAA structural stress correlated with 18F-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 18F-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 18F-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.