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[ 177 Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [ 177 Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [ 177 Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [ 177 Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer-associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [ 177 Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0-6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3-16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer-associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [ 177 Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence-based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To compare the diagnostic performance of [ 68 Ga]DOTATATE PET/CT, [ 18 F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases., Materials and Methods: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [ 68 Ga]DOTATATE PET/CT, [ 18 F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRI spine ), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRI WB ), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CT WB ). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported., Results: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRI spine were included who also underwent [ 68 Ga]DOTATATE PET/CT (n = 43), [ 18 F]FDG PET/CT (n = 43), MRI WB (n = 24), and CT WB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [ 68 Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [ 18 F]FDG (72.0%, 275/382, p < 0.001), MRI spine (80.6%, 308/382, p < 0.001), MRI WB (55.3%, 136/246, p < 0.001), and CT WB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [ 68 Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [ 18 F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRI spine (97.6%, 40/41, p = 1.00), MRI WB (95.7%, 22/23, p = 1.00), and CT WB (81.8%, 27/33, p = 0.03)., Conclusions: [ 68 Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate., Clinical Relevance Statement: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [ 68 Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [ 18 F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001)., Key Points: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [ 68 Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [ 18 ]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [ 68 Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objective: Primary hepatocellular carcinoma (HCC) poses a significant threat to human health. The mean overall survival (OS) of HCC is approximately 15.8 months whereas the 6-month and 1-year OS rates are only 71.6% and 49.7%, respectively. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the management of several solid cancers; however, HCC frequently displays low 18 F-FDG uptake; approximately 50% of HCC cases do not take up 18 F-FDG. Therefore, 18 F-FDG PET is not considered very useful for the visualization of HCC and is not currently a recommended standard imaging modality for HCC. Conversely, 18 F-FDG PET/CT has been reported to be clinically important in the management, staging, and prognosis of HCC patients. Currently, reports relating to 18 F-FDG uptake in HCC are unclear and controversial. There is an urgent need to clarify the efficacy of 18 F-FDG PET for the management of HCC., Methods: The PubMed database was searched for all articles on the application of 18 F-FDG PET/CT imaging for human HCC up to December 2021. The following search terms were used: 'Hepatocellular carcinoma', '[18F]FDG PET/CT', 'Hypoxia', '[ 11 C]Choline'., Key Content and Findings: In this review, we re-evaluate the potential hypoxia-dependent uptake mechanism of 18 F-FDG in HCC and review the usefulness of 18 F-FDG PET/CT for identifying, managing, and investigating the biological properties of HCC., Conclusions: 18 F-FDG PET/CT is very useful for HCC visualization, management, and the evaluation of biological properties. A negative test for 18 F-FDG uptake is not meaningless and may reflect a relatively better outcome. 18 F-FDG-positive lesions indicate a significantly less favorable prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1420/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Alzheimer's disease (AD) is the main cause of dementia, with its diagnosis and management remaining challenging. Amyloid positron emission tomography (PET) has become increasingly important in medical practice for patients with AD. To integrate and update previous guidelines in the field, a task group of experts of several disciplines from multiple countries was assembled, and they revised and approved the content related to the application of amyloid PET in the medical settings of cognitively impaired individuals, focusing on clinical scenarios, patient preparation, administered activities, as well as image acquisition, processing, interpretation and reporting. In addition, expert opinions, practices, and protocols of prominent research institutions performing research on amyloid PET of dementia are integrated. With the increasing availability of amyloid PET imaging, a complete and standard pipeline for the entire examination process is essential for clinical practice. This international consensus and practice guideline will help to promote proper clinical use of amyloid PET imaging in patients with AD., Competing Interests: Conflicts of InterestThe authors declare that they have no conflict of interest., (© The Author(s) 2022.)

The study identifies the importance of positron emission tomographic (PET) and anatomic imaging modalities and their individual performances in detecting succinate dehydrogenase A ( SDHA) -related metastatic pheochromocytoma and paraganglioma (PPGL). The detection rates of PET modalities- 68 Ga-DOTATATE, 18 F-FDG, and 18 F-FDOPA-along with the combination of computed tomography (CT) and magnetic resonance imaging (MRI) are compared in a cohort of 11 patients with metastatic PPGL in the setting of a germline SDHA mutation. The imaging detection performances were evaluated at three levels: overall lesions, anatomic regions, and a patient-by-patient basis. 68 Ga-DOTATATE PET demonstrated a lesion-based detection rate of 88.6% [95% confidence interval (CI), 84.3-92.5%], while 18 F-FDG, 18 F-FDOPA, and CT/MRI showed detection rates of 82.9% (CI, 78.0-87.1%), 39.8% (CI, 30.2-50.2%), and 58.2% (CI, 52.0-64.1%), respectively. The study found that 68 Ga-DOTATATE best detects lesions in a subset of patients with SDHA- related metastatic PPGL. However, 18 F-FDG did detect more lesions in the liver, mediastinum, and abdomen/pelvis anatomic regions, showing the importance of a combined approach using both PET modalities in evaluating SDHA -related PPGL.

Positron emission tomography (PET) represents molecular imaging for non-invasive phenotyping of physiological and biochemical processes in various oncological diseases. PET imaging with 18 F-fluorodeoxyglucose ( 18 F-FDG) for glucose metabolism evaluation is the standard imaging modality for the clinical management of lymphoma. One of the 18 F-FDG PET applications is the detection and pre-treatment staging of lymphoma, which is highly sensitive. 18 F-FDG PET is also applied during treatment to evaluate the individual chemo-sensitivity and accordingly guide the response-adapted therapy. At the end of the therapy regiment, a negative PET scan is indicative of a good prognosis in patients with advanced Hodgkin's lymphoma and diffuse large B-cell lymphoma. Thus, adjuvant radiotherapy may be alleviated. Future PET studies using non- 18 F-FDG radiotracers, such as 68 Ga-labeled pentixafor (a cyclic pentapeptide that enables sensitive and high-contrast imaging of C-X-C motif chemokine receptor 4), 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) that reflects the tumor microenvironment, and 89 Zr-labeled atezolizumab that targets the programmed cell death-ligand 1 (PD-L1), may complement 18 F-FDG and offer essential tools to decode lymphoma phenotypes further and identify the mechanisms of lymphoma therapy., Competing Interests: Conflicts of InterestThe authors declare that they have no conflicts of interest., (© International Human Phenome Institutes (Shanghai) 2022.)

Purpose: Positron emission tomography (PET) with the first and only tau targeting radiotracer of 18 F-flortaucipir approved by FDA has been increasingly used in depicting tau pathology deposition and distribution in patients with cognitive impairment. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform 18 F-flortaucipir PET imaging., Method: A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for 18 F-flortaucipir PET imaging in Alzheimer's disease (AD), focusing on clinical scenarios, patient preparation, and administered activities, as well as image acquisition, processing, interpretation, and reporting., Conclusion: This international consensus and practice guideline will help to promote the standardized use of 18 F-flortaucipir PET in patients with AD. It will become an international standard for this purpose in clinical practice., (© 2022. The Author(s).)

BACKGROUND . Recent professional society guidelines for radionuclide imaging of sporadic pheochromocytoma (PHEO) recommend 18 F-fluorodihydroxyphenylala-nine ( 18 F-FDOPA) as the radiotracer of choice, deeming 68 Ga-DOTATATE and FDG to be second- and third-line agents, respectively. An additional agent, 18 F-fluorodopamine ( 18 F-FDA), remains experimental for PHEO detection. A paucity of research has performed head-to-head comparison among these agents. OBJECTIVE . The purpose of this study was to perform an intraindividual comparison of 68 Ga-DOTATATE PET/CT, FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, CT, and MRI in visualization of sporadic primary PHEO. METHODS . This prospective study enrolled patients referred with clinical suspicion for sporadic PHEO. Patients were scheduled for 68 Ga-DOTATATE PET/CT, FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, whole-body staging CT (portal venous phase), and MRI within a 3-month period. PET/CT examinations were reviewed by two nuclear medicine physicians, and CT and MRI were reviewed by two radiologists; differences were resolved by consensus. Readers scored lesions in terms of confidence in diagnosis of PHEO (1-5 scale; 4-5 considered positive for PHEO). Lesion-to-liver SUV max was computed using both readers' measurements. Interreader agreement was assessed using intraclass correlation coefficients (ICCs) for SUV max . Analysis included only patients with histologically confirmed PHEO on resection. RESULTS . The analysis included 14 patients (eight women, six men; mean age, 52.4 ± 16.8 [SD] years) with PHEO. Both 68 Ga-DOTATATE PET/CT and FDG PET/CT were completed in all 14 patients, 18 F-FDOPA PET/CT in 11, 18 F-FDA PET/CT in 7, CT in 12, and MRI in 12. Mean conspicuity score for PHEO was 5.0 ± 0.0 for 18 F-FDOPA PET/CT, 4.7 ± 0.5 for MRI, 4.6 ± 0.8 for 18 F-FDA PET/CT, 4.4 ± 1.0 for 68 Ga-DOTATATE PET/CT, 4.3 ± 1.0 for CT, and 4.1 ± 1.5 for FDG PET/CT. The positivity rate for PHEO was 100.0% (11/11) for 18 F-FDOPA PET/CT, 100.0% (12/12) for MRI, 85.7% (6/7) for 18 F-FDA PET/CT, 78.6% (11/14) for FDG PET/CT, 78.6% (11/14) for 68 Ga-DOTATATE PET/CT, and 66.7% (8/12) for CT. Lesion-to-liver SUV max was 10.5 for 18 F-FDOPA versus 3.0-4.2 for the other tracers. Interreader agreement across modalities ranged from 85.7% to 100.0% for lesion positivity with ICCs of 0.55-1.00 for SUV max measurements. CONCLUSION . Findings from this small intraindividual comparative study support 18 F-FDOPA PET/CT as a preferred first-line imaging modality in evaluation of sporadic PHEO. CLINICAL IMPACT . This study provides data supporting current guidelines for imaging evaluation of suspected PHEO. TRIAL REGISTRATION . ClinicalTrials.gov NCT00004847.

Abstract: A 49-year-old woman from Cameroon presented with history of several months of worsening headache, lethargy, left arm weakness, and generalized lymphadenopathy. Brain MRI demonstrated multifocal signal abnormality and enhancement involving the bilateral basal ganglia and cerebral white matter. FDG PET/CT performed as part of lymphadenopathy evaluation demonstrated patchy areas of increased metabolic activity of the brain parenchyma. Human African trypanosomiasis or African sleeping sickness is a protozoan infection caused by Trypanosoma brucei gambiense transmitted by the tsetse fly in sub-Saharan Africa. It is important to recognize the signs and symptoms in nonendemic countries to facilitate early diagnosis and treatment., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Metastatic bladder cancer is an aggressive disease that can often be difficult to diagnose and stage with conventional cross-sectional imaging. The primary objective of this study was to determine the clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/MRI for surveillance and restaging of patients with muscle-invasive, locally advanced, and metastatic bladder cancer compared to conventional imaging methods., Materials and Methods: This retrospective study enrolled patients with muscle-invasive, locally advanced and metastatic bladder cancer in a single institute evaluated with 18 F-FDG PET/MRI. All patients also underwent conventional imaging with CT. Additional imaging may also have included 18 F-FDG PET/CT ( 18 F-FDG PET), or sodium fluoride (NaF) PET/CT in some patients. Images were reviewed by a diagnostic radiologist/nuclear medicine physician. Number of lesions and sites of disease were captured and compared between 18 F-FDG PET/MRI and conventional imaging. Lesions were confirmed by sequential imaging or lesion biopsy. All patients were followed for survival., Results: Fifteen patients (4 for surveillance; 11 for restaging) underwent 34 18 F-FDG PET/MRI scans. Each patient received a corresponding conventional CT around the time of the 18 F-FDG PET/MRI (median 6 days). The 15 patients (11 male; 4 female) had a median age of 61.5 years (range 37-73) and histologies of urothelial carcinoma (n = 13) and small-cell carcinoma of the bladder (n = 2) diagnosed as stage 4 (n = 13), stage 3 (n = 1), or stage 2 (n = 1). 18 F-FDG PET/MRI detected 82 metastatic malignant lesions involving lymph nodes (n = 22), liver (n = 10), lung (n = 34), soft tissue (n = 12), adrenal glands (n = 1), prostate (n = 1), and bone (n = 2) with a resultant advantage of 36% for lesion visibility in comparison with CT. Serial imaging or biopsy confirmed these lesions as malignant., Conclusion: 18 F-FDG PET/MRI can detect metastatic lesions which cannot be identified on conventional CT, and this can allow for better treatment planning and improved disease monitoring during therapy., (Published by Elsevier Inc.)

Purpose: Positron emission tomography (PET) with 18 F-fluorodeoxyglucose ([ 18 F]-FDG) has been increasingly applied in precise localization of epileptogenic focus in epilepsy patients, including pediatric patients. The aim of this international consensus is to provide the guideline and specific considerations for [ 18 F]-FDG PET in pediatric patients affected by epilepsy., Methods: An international, multidisciplinary task group is formed, and the guideline for brain [ 18 F]-FDG PET/CT in pediatric epilepsy patients has been discussed and approved, which include but not limited to the clinical indications, patient preparation, radiopharmaceuticals and administered activities, image acquisition, image processing, image interpretation, documentation and reporting, etc. CONCLUSION: This is the first international consensus and practice guideline for brain [ 18 F]-FDG PET/CT in pediatric epilepsy patients. It will be an international standard for this purpose in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

First introduced in 1976, 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) has become an indispensable tool for diagnosis and prognostic evaluation of tumors, heart disease, as well as other conditions, including inflammation and infection. Because 18 F-FDG can accurately reflect the glucose metabolism level of organs and tissues, it is known as a "century molecule" and is currently the main agent for PET imaging. The degree of 18 F-FDG uptake by cells is related to both the rate of glucose metabolism and glucose transporter expression. These, in turn, are strongly influenced by hypoxia, in which cells meet their energy needs through glycolysis, and 18 F-FDG uptake increased due to hypoxia. 18 F-FDG uptake is a complex process, and hypoxia may be one of the fundamental driving forces. The correct interpretation of 18 F-FDG uptake in PET imaging can help clinics make treatment decisions more accurately and effectively. In this article, we review the application of 18 F-FDG PET in tumors, myocardium, and inflammation. We discuss the relationship between 18 F-FDG uptake and hypoxia, the possible mechanism of 18 F-FDG uptake caused by hypoxia, and the associated clinical implications.

Purpose: To assess differences in FDG-PET/CT uptake among four subtypes of renal tumors: clear cell RCC (ccRCC), papillary type I and II RCC (pRCC), and oncocytoma., Methods: This retrospective study investigated 33 patients with 98 hereditary renal tumors. Lesions greater than 1 cm and patients with a timeframe of less than 18 months between preoperative imaging and surgery were considered. FDG-PET/CT images were independently reviewed by two nuclear medicine physicians, blinded to clinical information. Volumetric lesion SUV mean was measured and used to calculate a target-to-background ratio respective to liver (TBR). The Shrout-Fleiss intra-class correlation coefficient was used to assess reliability between readers. A linear mixed effects model, accounting for within-patient correlations, was used to compare TBR values of primary renal lesions with and without distant metastasis., Results: The time interval between imaging and surgery for all tumors had a median of 77 (Mean: 139; Range: 1-512) days. Intra-class reliability of mean TBR resulted in a mean κ score of 0.93, indicating strong agreement between the readers. The mixed model showed a significant difference in mean TBR among the subtypes (p < 0.0001). Pairwise comparison showed significant differences between pRCC type II and ccRCC (p < 0.0001), pRCC type II and pRCC type I (p = 0.0001), and pRCC type II and oncocytoma (p = 0.0016). Furthermore, a significant difference in FDG uptake was present between primary pRCC type II renal lesions with and without distant metastasis (p = 0.023)., Conclusion: pRCC type II lesions demonstrated significantly higher FDG activity than ccRCC, pRCC type I, or oncocytoma. These findings indicate that FDG may prove useful in studying the metabolic activity of renal neoplasms, identifying lesions of highest clinical concern, and ultimately optimizing active surveillance, and personalizing management plans.

Targeted radionuclide therapies (TRT) using 131 I-metaiodobenzylguanidine ( 131 I-MIBG) and peptide receptor radionuclide therapy ( 177 Lu or 90 Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity- 131 I-MIBG therapy was approved by the FDA and both 177 Lu-DOTATATE and 131 I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs., (©2021 American Association for Cancer Research.)

Context: Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumors that can secrete norepinephrine (NE). Brown adipose tissue (BAT) activation is mediated through the action of NE on β-adrenoceptors (β-ARs). In some malignancies, BAT activation is associated with higher cancer activity., Objective: To study the relationship between BAT activation and PPGL clinical outcomes., Design: A retrospective case-control study that included 342 patients with PPGLs who underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET/CT) imaging at the National Institutes of Health (NIH). We excluded all patients with parasympathetic tumors and those who underwent 18F-FDG PET/CT after PPGL resection. Scans of 205 patients were reviewed by 2 blinded nuclear medicine physicians; 16 patients had BAT activation on 18F-FDG PET/CT [7.80%; age 27.50 (15.00-45.50) years; 10 female/6 male; body mass index [BMI] 24.90 [19.60-25.35] kg/m2). From the remaining 189 patients, we selected 36 matched controls (age 34.4 [25.4-45.5] years; 21 female/15 male; BMI 25.0 [22.0-26.0] kg/m2)., Primary Outcome Measure: Overall survival., Results: The presence of active BAT on 18F-FDG PET/CT was associated with decreased overall survival when compared with the control group (HRz 5.80; 95% CI, 1.05-32.05; P = 0.02). This association remained significant after adjusting for the SDHB mutation. Median plasma NE in the BAT group was higher than the control group [4.65 vs 0.55 times above the upper limit of normal; P < 0.01]. There was a significant association between higher plasma NE levels and mortality in PPGLs in both groups., Conclusions: Our findings suggest that the detection of BAT activity in PPGL patients is associated with higher mortality. We suggest that BAT activation could either be reflecting or contributing to a state of increased host stress that may predict poor outcome in metastatic PPGL., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Objective: Disease activity in large-vessel vasculitis (LVV) is traditionally assessed by clinical and serological variables rather than vascular imaging. This study determined the effect of treatment on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) vascular activity in relation to clinical- and serologic-based assessments., Methods: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TA) were prospectively evaluated at 6-month intervals in an observational cohort. Treatment changes were made at least 3 months before the followup visit and categorized as increased, decreased, or unchanged. Imaging (FDG-PET qualitative analysis), clinical, and serologic (erythrocyte sedimentation rate, C-reactive protein) assessments were determined at each visit and compared over interval visits., Results: Serial assessments were performed in 52 patients with LVV (GCA = 31; TA = 21) over 156 visits. Increased, decreased, or unchanged therapy was recorded for 36-, 23-, and 32-visit intervals, respectively. When treatment was increased, there was significant reduction in disease activity by imaging, clinical, and inflammatory markers (p ≤ 0.01 for each). When treatment was unchanged, all 3 assessments of disease activity remained similarly unchanged over 6-month intervals. When treatment was reduced, PET activity significantly worsened (p = 0.02) but clinical and serologic activity did not significantly change. Treatment of GCA with tocilizumab and of TA with tumor necrosis factor inhibitors resulted in significant improvement in imaging and clinical assessments of disease activity, but only rarely did the assessments both become normal., Conclusion: In addition to clinical and serologic assessments, vascular imaging has potential to monitor disease activity in LVV and should be tested as an outcome measure in randomized clinical trials.

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Pheochromocytoma and paraganglioma (PHEO/PGL) are rare neuroendocrine tumors which may cause potentially life-threatening complications, with about a third of cases found to harbor specific gene mutations. Thus, early diagnosis, treatment, and meticulous monitoring are of utmost importance. Because of low incidence of succinate dehydrogenase complex subunit A ( SDHA )-related metastatic PHEO/PGL, currently there exists insufficient clinical information, especially with regards to its diagnostic and treatment characteristics. Methods: Ten patients with SDHA -related metastatic PHEO/PGL were followed-up prospectively and/or retrospectively between January 2010-July 2018. They underwent biochemical tests ( n = 10), 123 I-MIBG ( n = 9) scintigraphy, and multiple whole-body positron emission tomography/computed tomography (PET/CT) scans with 68 Ga-DOTATATE ( n = 10), 18 F-FDG ( n = 10), and 18 F-FDOPA ( n = 6). Results: Our findings suggest that these tumors can occur early and at extra-adrenal locations, behave aggressively, and have a tendency to develop metastatic disease within a short period of time. None of our patients had a family history of PHEO/PGL, making them appear sporadic. Nine out of 10 patients showed abnormal PHEO/PGL-specific biochemical markers with predominantly noradrenergic and/or dopaminergic phenotype, suggesting their utility in diagnosing and monitoring the disease. Per patient detection rates of 68 Ga-DOTATATE ( n = 10/10), 18 F-FDG ( n = 10/10), 18 F-FDOPA ( n = 5/6) PET/CT, and 123 I-MIBG ( n = 7/9) scintigraphy were 100, 100, 83.33, and 77.77%, respectively. Five out of 7 123 I-MIBG positive patients had minimal 123 I-MIBG avidity or detected very few lesions compared to widespread metastatic disease on 18 F-FDG PET/CT, implying that diagnosis and treatment with 123/131 I-MIBG is not a good option. 68 Ga-DOTATATE PET/CT was found to be superior or equal to 18 F-FDG PET/CT in 7 out of 10 patients and hence, is recommended for evaluation and follow-up of these patients. All 7 out of 7 patients who received conventional therapies (chemotherapy, somatostatin analog therapy, radiation therapy, 131 I-MIBG, peptide receptor radionuclide therapy) in addition to surgery showed disease progression. Conclusion: In our cohort of patients, SDHA -related metastatic PHEO/PGL followed a disease-course similar to that of SDHB -related metastatic PHEO/PGL, showing highly aggressive behavior, similar imaging and biochemical phenotypes, and suboptimal response to conventional therapies. Therefore, we recommend careful surveillance of the affected patients and a search for effective therapies.

Objectives: To assess agreement between interpretation of magnetic resonance angiography (MRA) and 18 F-fluorodeoxyglucose positron emission tomography (PET) for disease extent and disease activity in large-vessel vasculitis (LVV) and determine associations between imaging and clinical assessments., Methods: Patients with giant cell arteritis (GCA), Takayasu's arteritis (TAK) and comparators were recruited into a prospective, observational cohort. Imaging and clinical assessments were performed concurrently, blinded to each other. Agreement was assessed by per cent agreement, Cohen's kappa and McNemar's test. Multivariable logistic regression identified MRA features associated with PET scan activity., Results: Eighty-four patients (GCA=35; TAK=30; comparator=19) contributed 133 paired studies. Agreement for disease extent between MRA and PET was 580 out of 966 (60%) arterial territories with Cohen's kappa=0.22. Of 386 territories with disagreement, MRA demonstrated disease in more territories than PET (304vs82, p<0.01). Agreement for disease activity between MRA and PET was 90 studies (68%) with Cohen's kappa=0.30. In studies with disagreement, MRA demonstrated activity in 23 studies and PET in 20 studies (p=0.76). Oedema and wall thickness on MRA were independently associated with PET scan activity. Clinical status was associated with disease activity by PET (p<0.01) but not MRA (p=0.70), yet 35/69 (51%) patients with LVV in clinical remission had active disease by both MRA and PET., Conclusions: In assessment of LVV, MRA and PET contribute unique and complementary information. MRA better captures disease extent, and PET scan is better suited to assess vascular activity. Clinical and imaging-based assessments often do not correlate over the disease course in LVV., Trial Registration Number: NCT02257866., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To evaluate and compare diagnostic performance of 68 Ga-DOTA(0)-Tyr(3)-octreotate ( 68 Ga-DOTATATE) with 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography-computed tomography (PET/CT) and anatomic imaging using computed tomography and/or magnetic resonance (CT/MR) imaging in detection of SDHx-related pheochromocytomas and paragangliomas (PPGLs) in pediatric patients., Methods: Nine pediatric patients (5:4, girls:boys; 14.6 ± 2.0 years) with an SDHx-related mutation (SDHB:SDHA:SDHD, n = 7:1:1) were included in this retrospective study. At the time of initial diagnosis, 7/9 patients had metastatic disease. They underwent CT/MR imaging along with PET/CT using 68 Ga-DOTATATE (n = 9), 18 F-FDG (n = 8), and positron emission tomography-magnetic resonance imaging (PET/MR) using 18 F-FDG (n = 1). In this manuscript, 18 F-FDG PET/CT refers to both 18 F-FDG PET/CT and 18 F-FDG PET/MR. The per-lesion, per-region, and per-patient detection rates were compared and calculated for each of the imaging modalities. A composite of all functional and anatomic imaging studies served as the imaging comparator., Results: Eight out of nine patients were positive for PPGLs on the imaging studies that demonstrated 107 lesions in 22 anatomic regions on the imaging comparator. The per-lesion detection rates for 68 Ga-DOTATATE PET/CT, 18 F-FDG PET/CT, and CT/MR imaging were 93.5% (95%CI, 87.0% to 97.3%); 79.4% (95%CI, 70.5% to 86.6%); and 73.8% (95%CI, 64.5% to 81.9%), respectively. The per-lesion detection rate for 68 Ga-DOTATATE PET/CT was significantly higher than that of 18 F-FDG PET/CT (p = 0.001) or CT/MR imaging (p < 0.001). In all of the anatomic regions except abdomen, the per-lesion detection rates for 68 Ga-DOTATATE PET/CT was found to be equal or superior to 18 F-FDG PET/CT, and CT/MR imaging. The per-region detection rate was 100% (95%CI, 84.6% to 100%) for 68 Ga-DOTATATE PET/CT and 90.9% (95%CI, 70.8% to 98.9%) for both 18 F-FDG PET/CT and CT/MR imaging. The per-patient detection rates for 68 Ga-DOTATATE PET/CT, 18 FDG PET/CT, and CT/MR imaging were all 100% (95%CI, 63.1% to 100%)., Conclusion: Our preliminary study demonstrates the superiority of 68 Ga-DOTATATE PET/CT in localization of SDHx-related PPGLs in pediatric population compared to 18 F-FDG PET/CT and CT/MR imaging with the exception of abdominal (excluding adrenal and liver) lesions, and suggests that it might be considered as a first-line imaging modality in pediatric patients with SDHx-related PPGLs.

Objective: To assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects., Methods: Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse., Results: A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months., Conclusion: FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse., (© 2017, American College of Rheumatology.)

Objectives: To quantify gross tumor volume (GTV) change during stereotactic body radiotherapy (SBRT) and on first follow-up, as well as to evaluate for any predictive prognostic risk factors related to GTV decrease. An attempt was also made to identify the potential timing for adaptive SBRT., Methods: Twenty-five tumors in 24 consecutive patients were treated with SBRT to total dose of 50 Gy in 5 fractions. Median age was 72.5 years. Tumor stage was T1, 68%; T2, 20%; and other, 12%. The GTVs of on the 5 cone-beam computed tomographies (CBCT1-5) obtained before each fraction and the first follow-up CT (CTPOST) were analyzed., Results: Median time from diagnosis to initiation of radiotherapy was 64 days. GTV on CBCT1 was the baseline for comparison. GTV decreased by a mean of 7% on CBCT2 (P=0.148), 11% on CBCT3 (P=0.364), 19% on CBCT4 (P=0.0021), and 32% on CBCT5 (P=0.0004). Univariate analyses of GTV shrinkage was significantly associated with "time from CBCT5 to CTPOST" (P=0.027) and "T-stage" (P=0.002). In multivariate analyses, "T-stage" remained significant with T1 tumors showing greater GTV shrinkage than T2 tumors., Conclusions: Significant decrease in GTV volume based on daily CBCT was demonstrated during SBRT treatment. Adaptive SBRT has the potential to minimize integral dose to the surrounding normal tissues without compromising GTV coverage.

Following tremendous economic progress, society in China is also undergoing fundamental changes, as is the healthcare system. Currently the training of Chinese young doctors and their future work placement are all undergoing re-structuring. We compiled some thoughts and opinions on the topic of 'should clinicians in China engage in research?', and publish them as a special report in this issue of Quantitative Imaging in Medicine and Surgery (QIMS). The contributors included some editorial members of this journal, and a few personal friends. Besides a few minor linguistic corrections, opinions from the contributors have not been edited, as we want authors' to write their own independent views. However, it is possible there is a selection bias of the contributors of this paper; more likely those who are interested in the medical research are selected and therefore the views of the contributors may not be generalizable. To compare the structure and funding of China with other countries, authors from UK, The Netherlands, France, and USA are also invited.

Unlabelled: This study revisited (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and its relationship to hypoxia in various tumor models., Methods: We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non-small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO2) of ascites fluid was measured. (18)F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections., Results: Ascites pO2 was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high (18)F-FDG uptake. In contrast, (18)F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver., Conclusions: Glucose demand ((18)F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of (18)F-FDG PET in oncology application., (Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.)

Osteonecrosis of the jaw is usually a potential complication of bisphosphonate therapy. In a cancer patient, this disease entity can be misdiagnosed as a metastatic lesion. Our aim is to make clinicians aware of bisphosphonate associated osteonecrosis of the jaw to prevent misdiagnosis and initiate proper treatment at the earliest. We present the case of a breast cancer patient with multiple bony metastases and a jaw lesion presumed to be metastases. After no response to palliative radiation, repeat radiological imaging studies revealed osteonecrosis of the jaw. Correlating a patient's clinical information with findings on diagnostic imaging studies, such as SPECT bone and CT scans, can help identify this potential complication of bisphosphonate treatment. Early diagnosis helps minimize unnecessary biopsies and allows for the proper treatment to be instituted.

Purpose: The objective is to validate the combination of 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) and (18)F-fluorodeoxyglucose ((18)F-FDG) as a "novel" positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical., Methods: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of (18)F-FDG, (18)F-FLT, and the cocktail of (18)F-FDG and (18)F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, (18)F-FDG PET and (18)F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, (18)F-FDG and (18)F-FLT cocktail PET scan was also performed in the mouse., Results: When injected individually, (18)F-FDG highly accumulated in hypoxic zones and high (18)F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlated with hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of (18)F-FDG and (18)F-FLT was generally mismatched in both rodents and patients. Combination of (18)F-FLT and (18)F-FDG appeared to map more cancer tissue than single-tracer PET., Conclusions: Combination of (18)F-FDG and (18)F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.

Focal increased lower thoracic spinal cord (18)F FDG uptake is not infrequently observed as a normal physiological finding and may be confused for spinal cord metastases. This study was conducted to evaluate a possible correlation between the lower thoracic (T11-T12) spinal uptake and lower limb movements/ambulatory status of the patients as a surrogate. The primary endpoint was to identify the possible cause(s) of the normal variant focal increased thoracic spinal cord (T11-T12) (18)F FDG activity and correlate it with the lower limb movements/ambulatory status of the patients. This was a retrospective analysis of PET-CT scans of 200 patients with solid and hematological malignancies. The focal relatively increased (18)F FDG activity in the lower thoracic spinal cord correlated strongly with the (18)F FDG intensity of the liver, bowel, C3-C5 cervical cord activity, weight of the patient and injected dose of (18)F FDG. With regard to the primary endpoint, no significant correlation was found between the ambulatory status of patients in any of the groups and thoracic spine SUVmax. This could be further assessed by performing dual studies in the same patient with and without moderate to excessive leg motion. Identifying this variant focal increased (18)F FDG activity can minimize errors of misdiagnosis and unnecessary further investigation.

The objective of this study was to determine whether (18)F-misonidazole could detect hypoxia in macroscopic and microscopic tumors in mice. In nude mice, subcutaneous xenografts and peritoneal metastases were generated utilizing human non-small cell lung cancer A549 and HTB177 cells. Animals were co-injected with (18)F-misonidazole, pimonidazole and bromodeoxyuridine, and tumor perfusion was assessed by Hoechst 33342 injection. The intratumoral distribution of (18)F-misonidazole was determined by micro-PET scan and autoradiography. Pimonidazole, bromodeoxyuridine and Hoechst 33342 were detected by immunohistochemistry on the autoradiography sections. Submillimeter micrometastases found to be severely hypoxic. In both peritoneal metastases and subcutaneous xenografts models, PET images displayed significant (18)F-misonidazole uptake, and its distribution was non-uniform in these macroscopic subcutaneous tumors. In frozen sections, digital autoradiography and immunohistochemistry revealed similar distributions of (18)F-misonidazole, pimonidazole and glucose transporter-1, in both microscopic and macroscopic tumors. Bromodeoxyuridine stained-positive proliferative regions were well perfused, as judged by Hoechst 33342, and displayed low (18)F-misonidazole accumulation. (18)F-misonidazole uptake was low in tumor stroma and necrotic zones as well. Microscopic non-small cell lung cancer metastases are severely hypoxic. (18)F-misonidazole PET is capable to image hypoxia noninvasively not only in macroscopic tumors but also in micrometastases growing in mice. Accordingly, (18)F-misonidazole may be a promising agent to detect the burden of micrometastatic diseases.

The incidence of osteonecrosis of the jaw (ONJ) among patients with cancer and metastatic bone disease being treated with bisphosphonates is as high as 10%, which dictates that an understanding of the risk factors, preventative measures, means of early diagnosis, and treatment is critical. Despite ONJ occurring in the clinical setting of intravenous bisphosphonates, there are other causes associated with higher risk of ONJ, such as multiple dental extractions. Overall, it is important for imaging health care professionals to recognize, describe, and understand ONJ to help minimize biopsies and allow proper treatment to begin as soon as possible.

Unlabelled: (18)F-FDG, (18)F-fluorothymidine, and (18)F-misonidazole PET scans have emerged as important clinical tools in the management of cancer; however, none of them have demonstrated conclusive superiority. The aim of this study was to compare the intratumoral accumulation of (18)F-FDG, (18)F-fluorothymidine, and (18)F-misonidazole and relate this to specific components of the tumor microenvironment in mouse models of human non-small cell lung cancer (NSCLC)., Methods: We used NSCLC A549 and HTB177 cells to generate subcutaneous and peritoneal xenografts in nude mice. Animals were coinjected with a PET radiotracer, pimonidazole (hypoxia marker), and bromodeoxyuridine (proliferation marker) intravenously 1 h before animal euthanasia. Tumor perfusion was assessed by Hoechst 33342 injection, given 1 min before sacrifice. The intratumoral distribution of PET radiotracers was visualized by digital autoradiography and related to microscopic visualization of proliferation, hypoxia, perfusion, stroma, and necrosis., Results: NSCLC xenografts had complex structures with intermingled regions of viable cancer cells, stroma, and necrosis. Cancer cells were either well oxygenated (staining negatively for pimonidazole) and highly proliferative (staining positively for bromodeoxyuridine) or hypoxic (pimonidazole-positive) and noncycling (little bromodeoxyuridine). Hypoxic cancer cells with a low proliferation rate had high(18)F-FDG and (18)F-misonidazole uptake but low (18)F-fluorothymidine accumulation. Well-oxygenated cancer cells with a high proliferation rate accumulated a high level of (18)F-fluorothymidine but low (18)F-FDG and(18)F-misonidazole. Tumor stroma and necrotic zones were always associated with low (18)F-FDG, (18)F-misonidazole, and (18)F-fluorothymidine activity., Conclusion: In NSCLC A549 and HTB177 subcutaneously or intraperitoneally growing xenografts, (18)F-fluorothymidine accumulates in well-oxygenated and proliferative cancer cells, whereas (18)F-misonidazole and (18)F-FDG accumulate mostly in poorly proliferative and hypoxic cancer cells. (18)F-FDG and (18)F-misonidazole display similar intratumoral distribution patterns, and both mutually exclude (18)F-fluorothymidine.

Objective: To evaluate the utility of (99m)Tc-fanolesomab (a (99m)Tc-labeled murine monoclonal immunoglobulin M antibody that specifically binds cluster designation 15 antigens on human neutrophillic leukocytes with high sensitivity and specificity) in diagnosing localized infections., Methods: Five patients with renal allografts were imaged using (99m)Tc-fanolesomab to look for a source of infection. Images were obtained between 2 and 4 h after injection of fanolesomab labeled with 15-20 mCi (99m)Tc. Imaging results were correlated with patients' culture results and clinical outcome., Results: Two patients showed a significant increase in renal allograft uptake and were found to have allograft pyelonephritis. One patient who developed a severe acute renal failure secondary to humoral rejection (antidonor human leukocyte antigen antibody-mediated rejection with polymorphonuclear capillaritis and glomerulitis) showed uptake similar to the lower lumbar spine. One patient with normal allograft function showed a significantly increased uptake, especially in the pelvis of the allograft, indicating normal excretion of the free (99m)Tc-pertechnetate by the allograft. The fifth patient who had been off immunosuppressive therapy and on maintenance hemodialysis for 4 months showed tracer uptake similar to the lumbar spine, suggestive of chronic allograft rejection., Conclusion: This preliminary study describes different patterns of (99m)Tc-fanolesomab scan in renal allografts during episodes of kidney infection, rejection, or normal function. It suggests that (99m)Tc-fanolesomab can be used to evaluate renal allograft complications.

Intracranial artery angioplasty and stenting are generally performed for ipsi-territory stroke prevention in stenotic disease; however, few options exist for chronic occlusion of a proximal feeding vessel. In such circumstances intracranial angioplasty and stenting of a neighboring vascular field may improve collateral flow to the territory of the occluded vessel. A case of basilar artery (BA) stenting is presented, performed to improve collateral flow in a man experiencing recurrent middle cerebral artery (MCA) strokes, despite superior temporal artery (STA)-MCA bypass for internal carotid artery occlusion. Following BA stenting, the patient had complete cessation of MCA ischemia and improved cerebrovascular reserve by single photon emission CT. BA stenting was found to be a safe and effective means of improving collateral flow to mitigate recurrent MCA infarctions. Far field interventions should be considered in selected patients who fail other treatments.