Median Standardized Uptake Value Research Articles

Ten-Year Experience in Implementing Single-Fraction Lung SBRT for Medically Inoperable Early-Stage Lung Cancer.

To review 10 years of using single-fraction lung stereotactic body radiation therapy (SF-SBRT) for medically inoperable peripheral early-stage lung cancer. An institutional review board-approved prospective lung SBRT data registry was surveyed until the end of December 2019 for all patients receiving SF-SBRT with minimum 6-month follow-up. Doses used were either 34 Gy or 30 Gy. Outcomes of interest included rates of local failure and overall survival (OS), as well as treatment-related toxicity graded per Common Terminology Criteria for Adverse Events version 3.0. A total of 229 patients met the study criteria. Patient characteristics included female sex (55%); median age, 74.6 years (range, 47-94); and median Karnofsky Performance Status 80 (range, 50-100). Tumor characteristics included median diameter, 1.6 cm (range, 0.7-4.1); median positron emission tomography standardized uptake value maximum 6.1 (range, 0.8-24.3); and 63.6% of patients biopsied. SF-SBRT dose was 34 Gy in 72.1% cases and 30 Gy in 27.9%, with patient and tumor characteristics balanced between cohorts. Overall median follow-up times for 30 Gy and 34 Gy were 36.7 and 17.2 months, respectively (P < .0001). At analysis, 55.9% patients were alive. Two (0.9%) patients developed grade 3 toxicities, and none had grade 4/5 toxicities. Grades 1 to 2 pneumonitis and chest wall toxicity were seen in 7% and 12.7% patients, respectively. Median overall survival was 44.1 months. Rates of 2-year local, nodal, and distant failure were 7.3%, 9.4%, and 12.2%, respectively. There were no significant differences in outcomes by dose. This is the largest institutional series to date reporting on SF-SBRT outcomes for medically inoperable peripheral early-stage lung cancer and the first to report on a decade's experience in implementing this schedule. Outcomes from this analysis are comparable to published results from 2 randomized trials and validate the use of this schedule in routine practice. In the absence of phase 3 trials, this study should encourage increased use of SF-SBRT for inoperable tumors.

Abstract P103: Molecular Imaging Analysis Of Integrin αvβ3 Expression With Gallium-68-labeled Arg-gly-asp In A Murine Model Of Thoracic Aortic Aneurysms

Background/Objective: Angiogenesis is a complex process. Studies in aneurysmal aortic wall in human tissue and animal models have demonstrated an increased mural neovascularization, and Integrin αVβ3 is a molecular indicator of angiogenesis. We aim to study and characterize Integrin αVβ3 expression with Gallium-68(68Ga)-labeled Arg-Gly-Asp (RGD) as a potential radiotracer using micro Positron Emission Tomography (PET) in a Murine model of Thoracic Aortic Aneurysms (TAA). Methods: Eight specimens of Wistar rat with Calcium Chloride (CaCl) TAA-induced were evaluated. The equipment utilized was an Albira microPET/CT unit (Bruker, Spain), access was obtained in one of the caudal veins for the radiolabeled 68Ga-RGD infusion. The PET uptake and activity were expressed as median value with interquartile range and the Mann-Whitney U test was employed to analyze and compare the chemically induced-site (Aneurysm) and intact aortic tissue (Control) in the same specimens. Statistical analysis was performed with GraphPad Prism 8.0 software. Results: All specimens tolerated well the procedures through a left thoracotomy (Upper panel figure A, B), and underwent imaging studies. A focal increased uptake was observed in the thoracic aortic lesions compared to control regions. The median standard uptake value (SUV) of 68Ga-RGD in the chemically induced-injury site (aneurysm) was 0.0125, while the uptake in the intact site (control) was 0.0003 (P value=0.0117) during a mean follow up period of 32 days (Lower panel figure A-C). Conclusion: We found significant differences of Integrin αVβ3 expression uptake with microPET imaging in chemically induced aneurysms and the intact aortic tissue within 5 weeks of vessel injury. Longitudinal studies with this imaging modality may assist in the molecular characterization of angiogenesis and aneurysmal progression in animal models, and its potential translation in clinical research studies in human patients with aortic aneurysm.

68Ga-DOTATOC-PET/MRI-A Secure One-Stop Shop Imaging Tool for Robotic Radiosurgery Treatment Planning in Patients with Optic Nerve Sheath Meningioma.

Simple SummaryThrough combined information about spatial spread in magnetic resonance imaging (MRI) and positron emission tomography (PET), gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) PET/MRI before radiosurgery allows safe treatment planning for optic nerve sheath meningiomas (ONSM). Moreover, because of specific receptor stocking, diagnostic accuracy is improved without the need for biopsy. Thus, Ga68-DOTATOC-PET/MRI can be considered a safe “one-stop shop” image tool prior to radiosurgery for ONSM.Optic nerve sheath meningiomas (ONSM) are rare but can lead to irreversible blindness. Hybrid imaging may enhance tumor delineation and diagnostic accuracy via receptor binding. However, relevant clinical data for ONSM are lacking. We evaluated the feasibility of receptor-based hybrid imaging prior to robotic radiosurgery (RRS). We retrospectively analyzed all of our institution’s patients with suspected ONSM who underwent combined positron emission tomography and magnetic resonance imaging (PET/MRI) with gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) before RRS between 2018 and 2019. Eight patients with ten suspected ONSM (female = 7; median age, 51.2 years; IQR, 43.0–66.0) were included. Nine out of ten ONSM were deemed PET-positive with a median standard uptake value (SUV) max of 5.6 (IQR, 2.6–7.8). For all nine ONSM that presented 68Ga-DOTATOC uptake, hybrid PET/MRI was used for target volume contouring prior to RSS. At a median follow-up of 11.7 months (IQR, 9.4–16.4), tumor control was achieved in all patients. Radiosurgery resulted in the improvement of visual acuity in two of eight patients, whereas six showed stable vision. Ga68-DOTATOC-PET/MRI can be used for target volume contouring prior to RRS for ONSM as it enables safe treatment planning and improves diagnostic accuracy.

PET/CT Guided Biopsy for the Diagnosis of Lymphoma

Introduction. Biopsy of affected tissue is required for lymphoma diagnosis at onset and relapse and to plan an adequate treatment. Open incisional biopsy is traditionally the method of choice, with an accuracy of approximately 100%. Nevertheless, it requires hospitalization, availability of an operating room and sometimes general anesthesia and is associated with several drawbacks (morbidity, surgical complications, tumor contamination of surrounding tissues). The development of ultrasound and computed tomography (CT)-guided fine-needle biopsies has almost overcome these disadvantages. However, a variable proportion of non-diagnostic procedures is reported, leading to an accuracy that ranges between 50% and 80%. Functional imaging, such as fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is a procedure which can potentially be used to drive biopsy to the most metabolically active area within a lymph node or to extranodal masses which sometimes show no morphologically detectable changes on CT scan.Methods. This trial started at the beginning of 2016 and is still ongoing. One hundred patients with suspect lymphoma at onset or relapse are expected to be enrolled in 3 years, provided they show FDG-avid findings. Patients are excluded if pregnant, breastfeeding or in case a fine-needle PET/CT-guided biopsy is contraindicated. Patients are also excluded if a superficial and easily accessible lymph node is appreciated. Primary objective of the trial is to assess the diagnostic accuracy of the combined PET and CT-guided approach in driving a fine-needle biopsy. Diagnostic accuracy will be compared to published data concerning conventional imaging. Specimen adequacy (length of the specimen, amount of neoplastic infiltration, amount of fibrous or bony tissue) will also be evaluated. The trial is supported by the Italian Association for Cancer Research (Associazione Italiana per la Ricerca sul Cancro, Progetto AIRC IG 2015 Id 17781).Results. Data are available for the first 32 patients enrolled (15 patients with a suspect of relapsed lymphoma and 17 with the suspect of newly onset of disease). Thirty-four procedures have been performed, 29 of them on an outpatient basis. Three procedures (8.8%) were interrupted because of unbearable pain, but could be successfully repeated in 2 cases without any complications. Pain was however always transient and never required pharmacological interventions. Biopsy target was a lymph node in 19 cases and an extranodal site in 13 (bone tissue in 8 cases, soft tissue in 3, liver and kidney in 1 each). Median standard uptake value (SUVmax) of target lesions was 11.5 (range 4.9-37.7). Insufficient samples were obtained in 9.7% of cases (3 patients), whereas in all other instances the tissue was considered adequate to formulate a diagnosis (table), including fluorescence in situ hybridization and molecular analyses, where appropriate. Mean sample length was 10 (± 1) mm (range 3-30 mm, standard deviation ± 6 mm). The mean amount of affected tissue in collected samples was 56 (standard deviation ± 33%) and the mean proportion of fibrosis or bone was 37% (standard deviation ± 32%). No severe adverse events were reported during or after each procedure and no patients required intensive monitoring after the intervention.Conclusions. Patients can benefit from a minimally invasive procedure which allows a timely and accurate diagnosis of lymphoma at onset or relapse. Cost and time savings will be evaluated once enrolment is fully completed. [Display omitted] DisclosuresZinzani:Celgene, Roche, Janssen, Gilead, Takeda, BMS, MSD, Servier, Sandoz, Mundipharma: Honoraria; Merck: Consultancy, Other: Advisory board; Celgene, Janssen, Gilead, Roche, Takeda, BMS, MSD, Sandoz, Servier, Mundipharma: Speakers Bureau.

OP0272 68GA-FAPI-04 PET/CT STUDY EXTENSION FOR THE ASSESSMENT OF FIBROBLAST ACTIVATION AND RISK EVALUATION IN SYSTEMIC SCLEROSIS-RELATED INTERSTITIAL LUNG DISEASE

Background:Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis (SSc). To date, the progression of SSc-ILD is judged by the accrual of lung damage on computed tomography (CT) and functional decline (forced vital capacity). However, this approach does not directly assess the activity of tissue remodeling. Moreover, prediction of the course of ILD in individual SSc patients remains challenging. Fibroblast Activation Protein (FAP) is a specific, ex vivo validated marker for activated fibroblasts.Objectives:The aims of this study were: 1. To assess differences in the uptake of 68GA-FAPI 04 in SSc-ILD patients compared to controls, to analyze 2. whether 68GA-FAPI 04 uptake at baseline correlates with other risk factors of disease progression and 3. Whether 68GA-FAPI 04 uptake is associated with the course of SSc-ILD.Methods:Between September 2018 and April 2020, 21 patients with SSc-ILD confirmed by HRCT and onset of SSc-ILD within ≤ 5 years or signs of progressive ILD and 21 controls without ILD were consecutively enrolled. All participants underwent 68Ga-FAPI-04 PET/CT imaging and standard-of-care procedures including HRCT and lung function testing (PFT) at baseline. Patients with SSc-ILD patients were followed-up for 6 months with HRCT and PFT. Follow-up 68Ga-FAPI-04 PET/CT scans were obtained in a subset of patients treated with nintedanib. We compared baseline 68Ga-FAPI-04 PET/CT uptake to standard diagnostic tools and currently used predictors of ILD progression. The association of 68Ga-FAPI-04 uptake with changes in FVC was analyzed using mixed-effects models.Results:68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in SSc-ILD compared to controls with a median (q1-q3 interval) wlSUVmean of 0.8 (0.6 to 2.1) in the SSc-ILD group and 0.5 (0.4 to 0.5) in the control group (p&lt;0.0001 with Mann-Whitney test) and a median whole lung maximal standardized uptake value (wlSUVmax) of 4.4 (3.05 to 5.2) in the SSc-ILD group compared to 0.7 (0.65 to 0.7) in the control group (p&lt;0.0001). wlFAPI-MAV and wlTL-FAPI were not measurable in control subjects, as no 68Ga-FAPI-04 uptake above background level was observed. In the SSc-ILD group the median wlFAPI-MAV was 254cm3 (163.4 to 442.3) and the median wlTL-FAPI was 183.6 cm3 (98.04 to 960.7). 68Ga-FAPI-04 uptake was higher in patients with extensive disease, with previous ILD progression or high EUSTAR activity scores. Increased 68Ga-FAPI-04 uptake at baseline was associated with progression of ILD independently of extent of involvement on HRCT scan and the forced vital capacity at baseline. In consecutive 68Ga-FAPI-04-PET/CTs, changes in 68Ga-FAPI-04 uptake was concordant with the observed response to the fibroblast-targeting antifibrotic agent nintedanib.Conclusion:Our study presents first in human evidence that 68Ga-FAPI-04-fibroblast uptake correlates with fibrotic activity and disease progression in the lungs of SSc-ILD patients and that 68Ga-FAPI-04-PET/CT may be of potential to improve risk assessment of SSc-ILD.Figure 1.A and B:68Ga-FAPI-04 PET/CT scan from a patient with SSc-ILD with selective 68Ga-FAPI-04 uptake in fibrotic areas of the left- and right lower lung lobes (red arrows), but not in non-fibrotic areas such as the middle lobe (green arrow). B Corresponding CT component.Acknowledgements:We gratefully acknowledge Prof. Uwe Haberkorn (University Hospital Heidelberg and DKFZ, Heidelberg, Germany) and iTheranostics Inc. (Dulles, VA, USA) for providing the precursor FAPI-04.Disclosure of Interests:Christina Bergmann: None declared, Jörg H.W. Distler Speakers bureau: Actelion, Anamar, ARXX, Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, and UCB, Grant/research support from: Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Christoph Treutlein: None declared, Koray Tascilar Speakers bureau: Gilead sciences GmbH, Pfizer Turkey, UCB Turkey, Anna-Theresa Mueller: None declared, Armin Atzinger: None declared, Alexandru-Emil Matei: None declared, Johannes Knitza: None declared, Andrea-Hermina Györfi: None declared, Anja Lueck: None declared, Clara Dees: None declared, Alina Soare: None declared, Andreas Ramming: None declared, Verena Schönau: None declared, Oliver Distler Speakers bureau: Arxx Therapeutics, Baecon Discovery, Blade Therapeutics,Bayer, Böhringer Ingelheim, Catenion,Competitive Drug Development International Ltd, Corbuspharma, CSL Behring, ChemomAb, Horizon Pharmaceuticals, Ergonex, Galaapagos NV, Glenmark Pharmaceuticals,GSK, Inventiva, Italfarmaco, IQvia, Kymera, Lilly, Medac, Medscape, MSD, Novartis, Pfizer, Roche, Sanofi, Taget Bio Sciencec, UCB, Grant/research support from: Bayer,Böhringer Ingelheim, Mitsubishi Tanabe Pharma, Olaf Prante: None declared, Philipp Ritt: None declared, Theresa Ida Goetz: None declared, Markus Koehner: None declared, Michael Cordes: None declared, Tobias Baeuerle: None declared, Torsten Kuwert Speakers bureau: Honoraria for occasional lectures by Siemens Healthineers, Grant/research support from: Research grant to the Clinic of Nuclear Medicine by this entity covering projects in the field of SPECT/CT, Georg Schett: None declared, Christian Schmidkonz: None declared

Is positron emission tomography/magnetic resonance imaging a reliable tool for detecting vascular activity in treated childhood-onset Takayasu's arteritis? A multicentre study.

Toassess whether 18F-fluordeoxiglucose (18F-FDG) PET/MRI) with angiographic sequences can contribute to detecting vessel wall inflammation in patients with childhood-onset Takayasu's arteritis (c-TA) under immunosuppressive therapy. A three-centre cross-sectional study was conducted. 18F-FDG PET/MRI scans were performed in c-TA patients and in oncologic patients, who served as the control group. Clinical and laboratory characteristics were also analysed. Seventeen c-TA patients (65% females) between the ages of 6 and 21 years with a mean disease duration of 9.4 years were recruited. Only one patient presented clinical disease activity and six (35.6%) had increased ESR and/or CRP levels. The most frequent magnetic resonance angiography (MRA) findings were stenosis and thickening, observed in 82.4 and 70.6% of c-TA patients, respectively. 18F-FDG PET revealed 18F-FDG uptake greater than the liver in at least one arterial segment in 15 (88.2%) patients in a qualitative analysis and a median maximum standardized uptake value (SUVmax) of 3.22 (interquartile range 2.76-3.69) in a semi-quantitative analysis. c-TA patients presented significantly higher SUVmax values than oncologic patients (P < 0.001). A positive correlation between SUVmax and CRP levels (ρ = 0.528, P = 0.029) was seen. A state-of-the-art imaging modality was used in c-TA patients and revealed a strong arterial FDG uptake even in patients in apparent remission. We suppose that this finding may represent silent activity in the vessel wall; however, we cannot exclude the possibility of arterial remodelling. Importantly, a negative imaging scan may help in immunosuppression withdrawal in daily clinical practice.

68Ga-DOTATOC PET/CT Follow Up after Single or Hypofractionated Gamma Knife ICON Radiosurgery for Meningioma Patients.

68Ga-DOTATOC represents a useful tool in tumor contouring for radiosurgery planning. We present a case series of patients affected by meningiomas on who we performed 68Ga-DOTATOC positron emission tomography (PET)/CT pre-operatively, a subgroup of which also underwent a post-operative 68Ga-DOTATOC PET/CT to evaluate the standardized uptake value (SUV) modification after Gamma Knife ICON treatment in single or hypofractionated fractions. Twenty patients were enrolled/included in this study: ten females and ten males. The median age was 52 years (range 33–80). The median tumor diameter was 3.68 cm (range 0.12–22.26 cm), and the median pre-radiotherapy maximum SUV value was 11 (range 2.3–92). The average of the relative percentage changes between SUVs at baseline and follow up was −6%, ranging from −41% to 56%. The SUV was reduced in seven out of 12 patients (58%), stable in two out of 12 (17%), and increased in three out of 12 (25%), suggesting a biological response of the tumor to the Gamma Knife treatment in most of the cases. 68Ga-DOTATOC-PET represents a valuable tool in assessing the meningioma diagnosis for primary radiosurgery; it is also promising for follow-up assessment.

18F-FDG-PET/CT Evaluation of Indeterminate Adrenal Masses in Noncancer Patients.

Adrenal tumors in noncancer patients are common. Evaluate performance of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) in distinguishing between benign and malignant adrenal tumors. Retrospective chart review 2010-2019. Academic institution. One hundred and seventeen noncancer patients, defined as having no history of cancer or with cancer in remission for ≥5 years, completed 18F-FDG-PET/CT to evaluate adrenal masses, with pathologic diagnoses or imaging follow-up (≥12 months). 18F-FDG-PET/CT of 117 indeterminate adrenal masses. Receiver operator characteristic curve of the ratios of adrenal lesion standardized uptake value (SUV)max to liver SUVmean and of adrenal lesion SUVmax to aortic arch blood pool SUVmean were constructed. Seventy benign and 47 malignant masses (35 adrenocortical carcinomas [ACCs], 12 adrenal metastases) were identified. Malignant masses had higher median liver SUV and blood pool SUV ratios than benign masses (6.2 and 7.4 vs 1.4 and 2.0, P < .001). Median liver and blood pool SUV ratios of ACC (6.1 and 7.3, respectively) and metastases (6.7 and 7.7, respectively) were higher than those of than adenomas (1.4 and 2.2, P < .05 for all comparisons). Optimal liver SUV ratio to discern between benign and malignant masses was 2.5, yielding 85% sensitivity, 90% specificity, and 7 false negative results (including 3 ACCs). Optimal blood pool SUV ratio was 3.4, yielding 83% sensitivity, 90% specificity, and 8 false negative results (including 4 ACCs). When used in conjunction with other clinical assessments, 18F-FDG-PET/CT can be a valuable tool in evaluating adrenal masses in noncancer patients.

FDG-PET assessment of the locus coeruleus in Alzheimer’s disease

Sensitive and reliable in vivo imaging of the locus coeruleus (LC) is important to develop and evaluate its potential as a biomarker in neurodegenerative diseases such as Alzheimer’s disease (AD). It is not known whether AD-related alterations in LC integrity can be detected using 18F-labelled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET). Mean FDG-PET images from AD patients (N ​= ​193) and controls (N ​= ​256) from the ADNI database were co-registered to a study-wise anatomical template. Regional LC median standardized uptake value ratio (SUVR) values were obtained using four previously published LC masks and normalized to values from pons and cerebellar vermis reference regions. To support the validity of our methods, other regions previously reported to be most and least affected metabolically in AD were also compared to controls. The LC did not show between-group differences in FDG-PET signal, whereas the mammillary bodies did, despite these regions having comparable volumes and SUVR ranges. Brain regions previously reported to be most and least affected metabolically in AD compared to controls showed medium-to-large and small effect sizes for SUVR differences respectively. The results do not support the current application of LC FDG-PET signal as an in vivo biomarker for AD. Methodological and demographic factors potentially contributing to these findings are discussed. Future research may investigate age-related differences in LC FDG-PET signal and higher resolution images to fully explore its biomarker potential.

68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study.

Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis. To date, the progression of systemic sclerosis-associated ILD is judged by the accrual of lung damage on CT and pulmonary function tests. However, diagnostic tools to assess disease activity are not available. Here, we tested the hypothesis that quantification of fibroblast activation by PET-CT using a 68Ga-labelled selective inhibitor of prolyl endopeptidase FAP (68Ga-FAPI-04) would correlate with ILD activity and disease progression in patients with systemic sclerosis-associated ILD. Between Sept 10, 2018, and April 8, 2020, 21 patients with systemic sclerosis-associated ILD confirmed by high-resolution CT (HRCT) within 12 months of inclusion and with onset of systemic sclerosis-associated ILD within 5 years or signs of progressive ILD and 21 controls without ILD were consecutively enrolled. All participants underwent 68Ga-FAPI-04 PET-CT imaging and standard-of-care procedures, including HRCT and pulmonary function tests at baseline. Patients with systemic sclerosis-associated ILD were followed for 6 months with HRCT and pulmonary function tests. We compared baseline 68Ga-FAPI-04 PET-CT uptake with standard diagnostic tools and predictors of ILD progression. The association of 68Ga-FAPI-04 uptake with changes in forced vital capacity was analysed using mixed-effects models. Follow-up 68Ga-FAPI-04 PET-CT scans were obtained in a subset of patients treated with nintedanib (follow-up between 6-10 months) to assess change over time. 68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in patients with systemic sclerosis-associated ILD compared with controls, with a median standardised uptake value (SUV) mean over the whole lung of 0·80 (IQR 0·60-2·10) in the systemic sclerosis-ILD group and 0·50 (0·40-0·50) in the control group (p<0·0001) and a mean whole lung maximal SUV of 4·40 (range 3·05-5·20) in the systemic sclerosis-ILD group compared with 0·70 (0·65-0·70) in the control group (p<0·0001). Whole-lung FAPI metabolic active volume (wlFAPI-MAV) and whole-lung total lesion FAPI (wlTL-FAPI) were not measurable in control participants, because no 68Ga-FAPI-04 uptake above background level was observed. In the systemic sclerosis-ILD group the median wlFAPI-MAV was 254·00 cm3 (IQR 163·40-442·30), and the median wlTL-FAPI was 183·60 cm3 (98·04-960·70). 68Ga-FAPI-04 uptake was higher in patients with extensive disease, with previous ILD progression, or high EUSTAR activity scores than in those with with limited disease, previously stable ILD, or low EUSTAR activity scores. Increased 68Ga-FAPI-04 uptake at baseline was associated with progression of ILD independently of extent of involvement on HRCT scan and the forced vital capacity at baseline. In consecutive 68Ga-FAPI-04 PET-CTs, changes in 68Ga-FAPI-04 uptake was concordant with the observed response to the fibroblast-targeting antifibrotic drug nintedanib. Our study presents the first in-human evidence that fibroblast activation correlates with fibrotic activity and disease progression in the lungs of patients with systemic sclerosis-associated ILD and that 68Ga-FAPI-04 PET-CT might improve risk assessment of systemic sclerosis-associated ILD. German Research Foundation, Erlangen Anschubs-und Nachwuchsfinanzierung, Interdisziplinäres Zentrum für Klinische Forschung Erlangen, Bundesministerium für Bildung und Forschung, Deutsche Stiftung Systemische Sklerose, Wilhelm-Sander-Foundation, Else-Kröner-Fresenius-Foundation, European Research Council, Ernst-Jung-Foundation, and Clinician Scientist Program Erlangen.

Role of [68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of peritoneal carcinomatosis and comparison with [18F]-FDG PET/CT.

The aim of this study was to explore the role of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT), compared with 18F-fluorodeoxyglucose [18F]-FDG PET/CT, for evaluating peritoneal carcinomatosis in patients with various types of cancer. Patients with suspected peritoneal malignancy, who underwent both [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT between October 2019 and August 2020, were retrospectively analysed. The radiotracer uptake, peritoneal cancer index (PCI) score, and diagnostic performance of [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were evaluated and compared. Our cohort consisted of 46 patients, including 16 patients with diffuse-type peritoneal carcinomatosis, 27 with nodular-type peritoneal carcinomatosis, and 3 true-negative patients. A significant difference in standard uptake values (SUV) of lesions between [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT examination was observed (median SUV: 3.48 vs. 9.82; P < 0.001), particularly in peritoneal carcinomatosis from gastric cancer (median SUV: 3.44 vs. 8.05; P = 0.001). Moreover, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a higher PCI score and better sensitivity than [18F]-FDG PET/CT for the detection of peritoneal carcinomatosis (6 vs. 18; P < 0.001; 72.09% vs. 97.67%; P = 0.002). [68Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated superior sensitivity over [18F]-FDG PET/CT for the detection of peritoneal carcinomatosis in patients with various types of cancer, particularly gastric cancer. Furthermore, the uptake of [68Ga]Ga-DOTA-FAPI-04 in peritoneal carcinomatosis was significantly higher than that of [18F]-FDG, demonstrating a larger extent of the lesions and yielding a higher PCI score. This could help enhance the image contrast, improve physicians' diagnostic confidence, and reduce the proportion of missed diagnoses.

Clinical and dosimetric predictors of radiation pneumonitis in early-stage lung cancer treated with Stereotactic Ablative radiotherapy (SABR) – An analysis of UK’s largest cohort of lung SABR patients

BackgroundStereotactic Ablative Radiotherapy (SABR) is the standard treatment for early-stage medically inoperable lung cancer. Predictors of radiation pneumonitis (RP) in patients treated with SABR are poorly defined. In this study, we investigate clinical and dosimetric parameters, which can predict symptomatic RP in early-stage lung cancer patients treated with SABR. Materials and methodsPatients treated with lung SABR between May 2009 and August 2018, in a single United Kingdom (UK) radiotherapy center were included. The patient's baseline characteristics, treatment details, and toxicity were retrieved from the electronic medical record. Dosimetric data was extracted from Xio and Monaco treatment planning systems. Patients were treated according to the UK SABR consortium guidelines. RP was graded retrospectively using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, based on available clinical and imaging information. Univariate and multivariate binary logistic regression was performed to determine predictive factors for grade ≥ 2 radiation pneumonitis, using Statistical Package for the Social Sciences (SPSS) statistics version 21 software. The goodness of fit was assessed using the Hosmer and Lemeshow test. The optimal diagnostic threshold was tested using the Receiver operating characteristics (ROC) curve. The chi-square test was carried out to test the different risk factors against the likelihood of developing grade ≥ 2 pneumonitis. ResultsA total of 1266 patients included in the analysis. The median age of patients was 75 years. Six hundred sixty-six patients (52.6%) were female. Median follow up was 56 months. Sixty-five percent of patients received 55 Gy in 5 fractions. Forty-three percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 and 16.2% had PS of 3. The Median Charlson comorbidity index was 6 (range 2–11). Median Standardized Uptake Value (SUV) max of the tumor was 6.5. Four hundred two patients (31.8%) had confirmed histological diagnosis; other patients were treated based on a radiological diagnosis. The median tumor size was 20 mm (range 4 mm–63 mm).Median Planning Target Volume (PTV) was 30.3 cc. Median values of R100, R50, and D2cm were 1.1, 5.6, 32.8 Gy. The median value of mean lung dose, V20, and V12.5 were 3.9 Gy, 5 %and 9.3% respectively.Eighty-five (6.7%) patients developed symptomatic RP (grade ≥ 2) with only 5(0.4%) developing grade 3 RP. Five percent of patients developed rib fractures but only 28% of these were symptomatic.On univariate analysis lower lobe tumor location, larger tumor size, PTV, mean lung dose, lung V20Gy, and V12.5 Gy were significantly associated with grade ≥ 2 RP. On multivariate analysis, only mean lung dose was associated with grade ≥ 2 pneumonitis.ROC curve analysis showed optimal diagnostic threshold for tumour size, PTV, mean lung dose, V20 and V12.5; are 22.5 mm ((Area Under Curve (AUC)-0.565)), 27.15 cc (AUC-0.58), 3.7 Gy (AUC-0.633), 4.6% (AUC-0.597), 9.5% (AUC-0.616). The incidence of ≥grade 2 RP was significantly high for values higher than the ROC threshold. ConclusionSABR treatment resulted in a very low rate of grade 3 pneumonitis. Lower lobe tumor location, larger tumor size, PTV, mean lung dose, V20, and V12.5 were found to be significant predictors of symptomatic radiation pneumonitis.

Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease

There is an urgent need for inexpensive and minimally invasive blood biomarkers for Alzheimer disease (AD) that could be used to detect early disease changes. To assess how early in the course of AD plasma levels of tau phosphorylated at threonine 217 (P-tau217) start to change compared with levels of established cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers of AD pathology. This cohort study included cognitively healthy control individuals (n = 225) and participants with subjective cognitive decline (n = 89) or mild cognitive impairment (n = 176) from the BioFINDER-2 study. Participants were enrolled at 2 different hospitals in Sweden from January 2017 to October 2019. All study participants underwent plasma P-tau217 assessments and tau- and amyloid-β (Aβ)-PET imaging. A subcohort of 111 participants had 2 or 3 tau-PET scans. Changes in plasma P-tau217 levels in preclinical and prodromal AD compared with changes in CSF P-tau217 and PET measures. Of 490 participants, 251 were women (51.2%) and the mean (SD) age was 65.9 (13.1) years. Plasma P-tau217 levels were increased in cognitively unimpaired participants with abnormal Aβ-PET but normal tau-PET in the entorhinal cortex (Aβ-PET+/ tau-PET- group vs Aβ-PET-/ tau-PET- group: median, 2.2 pg/mL [interquartile range (IQR), 1.5-2.9 pg/mL] vs 0.7 pg/mL [IQR, 0.3-1.4 pg/mL]). Most cognitively unimpaired participants who were discordant for plasma P-tau217 and tau-PET were positive for plasma P-tau217 and negative for tau-PET (P-tau217+/tau-PET-: 36 [94.7%]; P-tau217-/tau-PET+: 2 [5.3%]). Event-based modeling of cross-sectional data predicted that in cognitively unimpaired participants and in those with mild cognitive impairment, both plasma and CSF P-tau217 would change before the tau-PET signal in the entorhinal cortex, followed by more widespread cortical tau-PET changes. When testing the association with global Aβ load in nonlinear spline models, both plasma and CSF P-tau217 were increased at lower Aβ-PET values compared with tau-PET measures. Among participants with normal baseline tau-PET, the rates of longitudinal increase in tau-PET in the entorhinal cortex were higher in those with abnormal plasma P-tau217 at baseline (median standardized uptake value ratio, 0.029 [IQR, -0.006 to 0.041] vs -0.001 [IQR, -0.021 to 0.020]; Mann-Whitney U, P = .02). In this cohort study, plasma P-tau217 levels were increased during the early preclinical stages of AD when insoluble tau aggregates were not yet detectable by tau-PET. Plasma P-tau217 may hold promise as a biomarker for early AD brain pathology.

Investigation of Longitudinal Dose-weighted FDG-Positron Emission Tomography Metabolic Imaging Biomarkers (PET MIBs) of Radiation-associated Dysphagia in OPC Cohort

Head and neck cancer radiotherapy (RT) is associated with injury to dysphagia/aspiration at risk structures (DARS) with subsequent radiation-associated dysphagia (RAD). We sought to characterize the kinetics of standardized uptake values (SUV) derived from routine pre- and post-RT FDG-PET in DARS. We further sought to examine correlations between our proposed PET MIBs and Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated CTCAE-compatible modified barium swallow (MBS) grading scale of pharyngeal-stage dysphagia, in a subgroup of patients with standardly acquired MBS. Data for patients with oropharyngeal cancer (OPC) treated with RT (2005-2016) with available pre- & post-RT PET-CT scans, and DICOM-RT data, were retrospectively collected after an IRB approval. Analyzed DARS included soft palate (SP), genioglossus (GG), mylogeniohyoid complex (MGH), superior, middle and inferior constrictor muscles (SPC, MPC, and IPC) as well as ipsilateral (ipsi) and contralateral (contra) anterior bellies of digastric (DA) muscles. After CT-CT deformable image co-registration using commercial software (Velocity AI), DARS were sub segmented into smaller subvolumes based on the dose they received in 5 Gy increments, i.e. 0-5 Gy, 5-10 Gy subvolumes, etc. Volumetric as well as median dose-weighted SUV (calculated as: SUV * Planned DARS dose) were extracted from these whole and sub DARS volumes pre- & post-RT then compared using in-house algorithm. A corollary analysis was then performed on a subset of patients with prospectively collected DIGEST scores at 3-6-month post-RT (DIGEST 3-6ms) using Kruskal-Wallis tests. 904 DARS of 113 RT-treated OPC patients, were sub segmented & analyzed. DIGEST 3-6ms was reported for 39 patients as: grade 0-1, i.e. No or mild dysphagia (59%) or grade 2-3, i.e. moderate/severe (41%). Volumes and SUVmedian increased significantly after RT (p<0.0001) for all muscular DARS, including SPC, MPC, IPC, both DA, GG, and MGH complex, unlike soft palate that showed a decline in SUVmedian post-RT (p<0.0001). A Spearman rank correlation test showed a rising magnitude of delta-changes with higher DARS Dmean (p<0.05), e.g. IPC volume; ρ = 0.2, contra DA SUVmedian; ρ = 0.2, and MGH complex SUVmedian; ρ = 0.27. There was an increased likelihood of more severe dysphagia among patients with higher mean planned RT dose for all DARS (except MGH complex), more advanced cancer stage, those who received induction chemotherapy or reported some degree of dysphagia at presentation (p<0.05). Using multiple logistic regression to model DIGEST 3-6ms, SP Dmean, post-RT SP volume, post-RT, IPC SUVmedian, along with induction chemotherapy could adequately predict RAD severity; AUC = 0.86 (95% CI: 0.6-0.94; p<0.022). We sought to quantify pre- and post-RT FDG-PET metrics of DARS. Longitudinal kinetics of PET-derived metrics manifest dose-dependent changes that can potentially serve as MIBs of RAD measures using DIGEST score.

Post FDA approval analysis of 200 gallium-68 DOTATATE imaging: A retrospective analysis in neuroendocrine tumor patients.

Gallium-68 DOTATATE provides physiologic imaging and assists in disease localization for somatostatin receptor (SSTR) positive neuroendocrine tumor (NET) patients. However, questions regarding usefulness of gallium- 68 DOTATATE imaging in identifying the primary site in neuroendocrine tumors (NETS) of unknown primary, correlation of NET grade with median Standardized Uptake Value (SUV) and effects of long acting somatostatin analog on gallium-68 DOTATATE imaging quality needs to be evaluated.A single institution retrospective review of the first 200 NET patients with gallium-68 DOTATATE imaging from Dec 2016 to Dec 2017 was conducted. Questions related to NETs of unknown primary, correlation of Standardized Uptake Value (SUV) to Ki-67 (which signifies proliferation rate), the effects of long-acting systemic somatostatin analog (SSA) on SUV were part of our data analysis.From these 200 patients, 59.5% (119) were females, 40.5% (81) were males; the median age was 62 years. The following primary tumor sites were identified: small bowel-37.5%; pancreas-18.5%; bronchial-14%; colon-3.5%; rectum-2%; appendix-1.5%; adrenal-0.5%; prostate-0.5%; others-3% and unknown primary-19%. Mean hepatic SUV of the lesion with the greatest radiolabeled uptake in 96 patients was similar irrespective to exposure to long acting SSA. Patients exposed to long acting SSA had mean SUV of 31.3 vs 27.8 for SSA naïve patients. The difference was not statistically significant.Gallium-68 DOTATATE imaging seems to distinguished G3 NET from G1/G2 based on mean SUV, and also identified the primary tumor site in 17 of 38 (45%) patients with unknown primary. Systemic exposure to long acting SSA does not appear to influence mean SUV of gallium-68 DOTATATE scan.

Assessment of Brain Glucose Metabolism Following Cardiac Arrest by [18F]FDG Positron Emission Tomography.

Cardiac arrest (CA) patients who survived by cardiopulmonary resuscitation (CPR) can present different levels of neurological deficits ranging from minor cognitive impairments to persistent vegetative state and brain death. The pathophysiology of the resulting brain injury is poorly understood, and whether changes in post-CA brain metabolism contribute to the injury are unknown. Here we utilized [18F]fluorodeoxyglucose (FDG)-Positron emission tomography (PET) to study in vivo cerebral glucose metabolism 72h following CA in a murine CA model. Anesthetized and ventilated adult C57BL/6 mice underwent 12-min KCl-induced CA followed by CPR. Seventy-two hours following CA, surviving mice were intraperitoneally injected with [18F]FDG (~ 186µCi/200µL) and imaged on Molecubes preclinical micro-PET/computed tomography (CT) imaging systems after a 30-min awake uptake period. Brain [18F]FDG uptake was determined by the VivoQuant software on fused PET/CT images with the 3D brain atlas. Upon completion of Positron emission tomography (PET) imaging, remaining [18F]FDG radioactivity in the brain, heart, and liver was determined using a gamma counter. Global increases in brain [18F]FDG uptake in post-CA mice were observed compared to shams and controls. The median standardized uptake value of [18F]FDG for CA animals was 1.79 versus sham 1.25 (p < 0.05) and control animals 0.78 (p < 0.01). This increased uptake was consistent throughout the 60-min imaging period and across all brain regions reaching statistical significance in the midbrain, pons, and medulla. Biodistribution analyses of various key organs yielded similar observations that the median [18F]FDG uptake for brain was 7.04%ID/g tissue for CA mice versus 5.537%ID/g tissue for sham animals, p < 0.05). This study has successfully applied [18F]FDG-PET/CT to measure changes in brain metabolism in a murine model of asystolic CA. Our results demonstrate increased [18F]FDG uptake in the brain 72h following CA, suggesting increased metabolic demand in the case of severe neurological injury. Further study is warranted to determine the etiology of these changes.

The Role of 18F-FDG PET/MRI in the Assessment of Primary Intrahepatic Neoplasms

To evaluate the results of 18F-FDG PET/MRI in relation to the histopathologic subtypes and histologic grades of mass-forming primary intrahepatic neoplasms. We retrospectively evaluated 18F-FDG positron emission tomography/magnetic resonance imaging (PET/MRI) results for 39 patients with histopathologically confirmed primary hepatic neoplasms, 15 with mass-forming intrahepatic cholangiocarcinoma (ICC) and 24 with hepatocellular carcinoma (HCC). The apparent diffusion coefficient (ADC) and standardized uptake value (SUV) were analyzed in relation to the histopathologic diagnosis and histologic grade, including calculating the sensitivity and specificity of the imaging findings. The median SUV of ICC (6.0 [interquartile range, 5-10]) was significantly higher than that of HCC (4.0 [2.62-6.50]) (p = 0.002). An area under the curve (AUC) of 0.79 (95% confidence interval 0.649-0.932) had a sensitivity of 86.7% and a specificity of 67% at the best cut-off SUV of 4.41 to differentiate between ICC and HCC. ADC values did not differ significantly between HCCs and ICCs (p = 0.283). Both SUV and ADC values differed significantly between low-grade (well- and moderately differentiated) and high-grade (poorly differentiated) HCCs. Combining ADC and SUV further improved differentiation of low- from high-grade HCCs to a significant level (0.929). The SUV did not differ significantly between ICC histologic grades (p = 0.280), while the ADC differed significantly only between well and poorly differentiated ICCs (p = 0.004). Assessing primary hepatic neoplasms with 18F-Fluorodeoxyglucose PET/MRI may help to predict tumor grade and differentiate between types of intrahepatic neoplasms.

PET/CT in Disease Detection and Follow-up of Subcutaneous Involvement in Marginal Zone Lymphoma

BackgroundThe value of positron emission tomography/computed tomography (PET/CT) in the staging and assessment of treatment response in marginal zone lymphoma (MZL) lymphomas remains controversial. We investigated radiologic characteristics of subcutaneous MZL as imaged on PET/CT scans. Patients and MethodsFrom the records of a single medical center, for the years 2008 and 2017, we identified subcutaneous lesions in PET/CT scans of patients with histopathologically confirmed MZL in sites other than subcutaneous tissue. ResultsOf 571 scans of 178 patients, subcutaneous lesions were found in 20 (11%). Lesions were located in soft tissue structures, mainly along the lateral aspects of the buttocks, thighs and lower and upper back areas, the flank, and the shoulders. Median lengths of the long and short axes of the lesions were 2.0 (range, 1.1-6.0) cm and 0.8 (range, 0.3-2.0) cm, respectively. Median standardized maximum uptake value was 2.3 (range, 0.9-7.6). In 12 patients (60%), MZL was diagnosed at an early stage; 15 (75%) had lymph node involvement and 10 (50%) extranodal involvement. One had spleen and 2 had cutaneous involvement; none had gastric findings. ConclusionThe findings of this study support the usefulness of PET/CT in the detection of subcutaneous MZL as well as in staging and treatment decisions.

Changes in cerebral glucose metabolism caused by morphologic features of prodromal idiopathic normal pressure hydrocephalus

BackgroundDecreased cerebral glucose metabolism has been reported in idiopathic normal pressure hydrocephalus (iNPH). However, the timing of appearance in the preclinical stage of iNPH remains unknown. Herein, we evaluated the changes in regional cerebral glucose metabolism with respect to the characteristic morphologic features of iNPH.MethodsWe performed a cross-sectional study in > 2000 elderly patients who received a whole body 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning and recruited subjects with clinical and preclinical iNPH. We included 12 subjects with iNPH, 32 subjects with asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM), and 33 subjects with preclinical morphologic features of DESH (PMD). We previously reported that iNPH develops in the order of PMD (asymptomatic subjects with incomplete DESH), AVIM (asymptomatic subjects with DESH), and iNPH (symptomatic subjects with DESH). We measured the median regional standardized uptake value ratio (SUVR) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography images between the three groups and compared them with background-matched normal controls in the frontal lobes, temporal lobes, medial parietal lobes, striata, and thalami.ResultsIn the frontal and temporal lobes, the SUVR distributions of the PMD, AVIM, and PMD groups were significantly lower than for each NC (p < 0.05 for all). In the medial parietal lobes, the SUVR distributions were significantly higher in PMD and AVIM groups (p < 0.05 for all). In the thalami and striata, the SUVR distributions were significantly lower in the iNPH group (p < 0.05 for all).ConclusionsChanges in brain glucose metabolism in the cortices are observed in preclinical iNPH, while metabolic decline in the basal ganglia is only detected in clinical iNPH.

Incidence of Convexal Subarachnoid Hemorrhage in the Elderly: The Mayo Clinic Study of Aging

ObjectivesNontraumatic convexal subarachnoid hemorrhages in the elderly can be a manifestation of cerebral amyloid angiopathy associated with a high risk of future intracerebral hemorrhage. The incidence in the elderly population is unknown. Our objectives were to: 1) determine the incidence of convexal subarachnoid hemorrhage in a population-based study, and, 2) to compare apopolipoprotein-E genotype and amyloid positron emission tomographic (PET) imaging for those with versus without hemorrhage. MethodsBetween 11/29/2004 and 3/11/2017, 4462 individuals without hemorrhage at baseline participated in the population-based Mayo Clinic Study of Aging. We used the Rochester Epidemiology Project medical records-linkage system to identify intracerebral hemorrhages. Records and images were reviewed to identify convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and apopolipoprotein-E genotype were recorded. ResultsFour cases were identified. The incidence of convexal subarachnoid hemorrhage was 14.1 per 100,000 person years. Three occurred in women, median age, 79 (range: 71-84). One patient had coexisting cerebral microbleeds. Two participants developed a subsequent lobar intracerebral hemorrhage at a median of 4.75 years after convexal subarachnoid hemorrhage. The apopolipoprotein-E -allele combinations of the 4 were: 3/3, 3/3, 2/2, and 2/3. On Pittsburgh Compound B-PET imaging, median standardized uptake value ratio with convexal subarachnoid hemorrhage was 1.86 (range: 1.38-2.34). ConclusionsConvexal subarachnoid hemorrhage is rare in the older population, occurring with an incidence of about 14 per 100,000 person years. Yet, when present, it may be associated with a high risk of future intracerebral hemorrhage.