scholarly journals Implementing Systems Modelling and Molecular Imaging to Predict the Efficacy of BCL-2 Inhibition in Colorectal Cancer Patient-Derived Xenograft Models

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2978
Author(s):  
Alice C. O’Farrell ◽  
Monika A. Jarzabek ◽  
Andreas U. Lindner ◽  
Steven Carberry ◽  
Emer Conroy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fdg Pet ◽  
Colorectal Cancer Patient ◽  
Standard Uptake Value ◽  
Systems Model ◽  
Patient Derived Xenograft ◽  
Positron Emission ◽  
Systems Modelling ◽  
18F Fdg ◽  
Pdx Models

Resistance to chemotherapy often results from dysfunctional apoptosis, however multiple proteins with overlapping functions regulate this pathway. We sought to determine whether an extensively validated, deterministic apoptosis systems model, ‘DR_MOMP’, could be used as a stratification tool for the apoptosis sensitiser and BCL-2 antagonist, ABT-199 in patient-derived xenograft (PDX) models of colorectal cancer (CRC). Through quantitative profiling of BCL-2 family proteins, we identified two PDX models which were predicted by DR_MOMP to be sufficiently sensitive to 5-fluorouracil (5-FU)-based chemotherapy (CRC0344), or less responsive to chemotherapy but sensitised by ABT-199 (CRC0076). Treatment with ABT-199 significantly improved responses of CRC0076 PDXs to 5-FU-based chemotherapy, but showed no sensitisation in CRC0344 PDXs, as predicted from systems modelling. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were performed to investigate possible early biomarkers of response. In CRC0076, a significant post-treatment decrease in mean standard uptake value was indeed evident only in the combination treatment group. Radiomic CT feature analysis of pre-treatment images in CRC0076 and CRC0344 PDXs identified features which could phenotypically discriminate between models, but were not predictive of treatment responses. Collectively our data indicate that systems modelling may identify metastatic (m)CRC patients benefitting from ABT-199, and that 18F-FDG-PET could independently support such predictions.

Abstract 35: DVT Inflammation Assessed by 18F-FDG-PET/CT Predicts Subsequent Vein Wall Scarring

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chase W Kessinger ◽  
Ahmed Tawakol ◽  
Gregory R Wojtkiewicz ◽  
Peter K Henke ◽  
Ralph Weissleder ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Vena Cava ◽  
Standard Uptake Value ◽  
Vein Wall ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg ◽  
The Right ◽  
Fdg Pet Ct

Objective: While venous thrombosis (VT)-induced inflammation facilitates thrombus resolution, inflammation causes vein wall scarring (VWS). Recently, statins have shown to improve VT resolution and reduce VT inflammatory components. In this study, we hypothesized that early VT inflammation detected by 18F-FDG positron emission tomography/computed tomography (PET/CT) could predict subsequent late stage VWS, and would be attenuated by statin therapy. Methods: Stasis VT was induced in 8-12 week old male C57BL/6 mice (n=31) in either the right jugular vein (n=13) or inferior vena cava (IVC,n=18). Animals in the IVC VT cohort were randomized to statin (n=8) or control (n=10) treatment. Statin, rosuvastatin (5mg/kg), was administered by oral gavage, daily starting 24 hours prior to VT induction; control mice received saline. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG inflammation signals (standard uptake value=SUV) were measured in the thrombosed vein and compared to the sham-operated venous segments or treatment control. On day 14, mice were sacrificed and VT tissue was resected. Picrosirius red staining allowed measurement of collagen and vein wall thickness in VT sections. Results: FDG-PET/CT at day 2 revealed increased inflammation signal activity in jugular VT (SUV 1.43 ± 0.3 VT vs. 0.81 ± 0.3 contralateral vein, p<0.0001). Statin-treated mice showed a trend of decreased inflammation signal at day 2 in the IVC VT models (SUV 1.02 ± 0.1 statin VT vs. 1.42 ± 0.2 control VT, p=0.07). Day 14 histological analysis revealed significantly reduced vein wall injury in statin-treated animals (thickness, 32±9.4 μm statin; vs. 56.2±14.7 μm control, p=0.02). Day 2 FDG-PET inflammation in VT correlated positively with the magnitude of day 14 VWS (jugular VT, Spearman r=0.62, p=0.02; IVC VT r=0.74, p<0.001, respectively). Conclusions: Quantitative FDG-PET/CT imaging demonstrates that early in vivo VT inflammation predicts subsequent VWS, a driver of post-thrombotic syndrome (PTS). The overall findings strengthen: (i) the link between inflammation and PTS; (ii) the translational potential of FDG-PET inflammation to predict VWS and PTS; and (iii) the concept that statins and other anti-inflammatory therapies could reduce VWS and PTS.

scholarly journals Radiomics Features of 18F-Fluorodeoxyglucose Positron-Emission Tomography as a Novel Prognostic Signature in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 392
Author(s):  
Jeonghyun Kang ◽  
Jae-Hoon Lee ◽  
Hye Sun Lee ◽  
Eun-Suk Cho ◽  
Eun Jung Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Positron Emission Tomography ◽  
Fdg Pet ◽  
Emission Tomography ◽  
Gray Level ◽  
Prognostic Signature ◽  
Training Set ◽  
Positron Emission ◽  
18F Fdg ◽  
Validation Set

The aim of this study was to investigate the prognostic value of radiomics signatures derived from 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) in patients with colorectal cancer (CRC). From April 2008 to Jan 2014, we identified CRC patients who underwent 18F-FDG-PET before starting any neoadjuvant treatments and surgery. Radiomics features were extracted from the primary lesions identified on 18F-FDG-PET. Patients were divided into a training and validation set by random sampling. A least absolute shrinkage and selection operator Cox regression model was applied for prognostic signature building with progression-free survival (PFS) using the training set. Using the calculated radiomics score, a nomogram was developed, and its clinical utility was assessed in the validation set. A total of 381 patients with surgically resected CRC patients (training set: 228 vs. validation set: 153) were included. In the training set, a radiomics signature labeled as a rad_score was generated using two PET-derived features, such as gray-level run length matrix long-run emphasis (GLRLM_LRE) and gray-level zone length matrix short-zone low-gray-level emphasis (GLZLM_SZLGE). Patients with a high rad_score in the training and validation set had a shorter PFS. Multivariable analysis revealed that the rad_score was an independent prognostic factor in both training and validation sets. A radiomics nomogram, developed using rad_score, nodal stage, and lymphovascular invasion, showed good performance in the calibration curve and comparable predictive power with the staging system in the validation set. Textural features derived from 18F-FDG-PET images may enable detailed stratification of prognosis in patients with CRC.

scholarly journals Improved Quantification of 18F-FDG PET during 131I-Rituximab Therapy on Mouse Lymphoma Models after 131I Prompt Emission Correction

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 144
Author(s):  
Lee ◽  
Kim ◽  
Kim
Keyword(s):  
Mouse Model ◽  
Fdg Pet ◽  
Standard Uptake Value ◽  
Correction Method ◽  
Positron Emission ◽  
Emission Effect ◽  
18F Fdg ◽  
The Difference ◽  
Prompt Emission

18F-FDG Positron Emission Tomography (PET) is used to monitor tumor response to 131I-therapy, but is confounded by prompt emissions (284, 364, 637, and 723 keV) from 131I, particularly in animal PET imaging. We propose a method for correcting this emission in 18F-FDG PET. The 131I prompt emission effect was assessed within various energy windows and various activities. We applied a single gamma correction method to a phantom and in vivo mouse model. The 131I prompt emission fraction was 12% when 300 µCi of 131I and 100 µCi of FDG were administered, and increased exponentially with escalating 131I activity for all energy windows. The difference in spill-over ratio was reduced to <5% after 131I prompt emission correction. In the mouse model, the standard uptake value (SUV) did not differ significantly between FDG PET only (gold standard) and FDG PET after 131I prompt emission-correction, whereas it was overestimated by 38% before correction. Contrast was improved by 18% after 131I prompt emission correction. We first found that count contamination on 18F-FDG follow-up scans due to 131I spilled-over count after 131I rituximab tumor targeted therapy. Our developed 131I prompt emission-correction method increased accuracy during measurement of standard uptake values on 18F-FDG PET.

Comparison of 18F-FDG and 67Ga-citrate in sarcoidosis imaging

2008 ◽  
Vol 47 (01) ◽  
pp. 18-23 ◽  
Author(s):  
M. Wehrschuetz ◽  
B. Bisail ◽  
M. Woltsche ◽  
T. Schwarz ◽  
H. Lanz ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Complete Agreement ◽  
Pet Tracer ◽  
Positron Emission ◽  
Significant Difference ◽  
Kappa Value ◽  
18F Fdg ◽  
Primary Assessment ◽  
67Ga Citrate

SummaryAim: 67Ga citrate has been used long and successfully to diagnose and stage sarcoidosis. 18F-fluorodeoxyglucose (18F-FDG) has been suggested as a positron emission tomography (PET) tracer for sarcoidosis imaging. This study aimed to analyze possible advantages of 18F-FDG-PET over 67Ga citrate scintigraphy during the primary assessment of patients with sarcoidosis. Patients and methods: Twentyfour patients (11 men, 13 women, aged 52 years ±12.4) with histologically proven sarcoidosis were investigated with 18F-FDG and 67Ga citrate. Equipment included a fullring PET scanner (ECAT EXACT HR+, Siemens/CTI, Knoxville TN, USA) and a double-headed gamma camera (ECAM, Siemens, Illinois, USA) for scintigraphy. The mean time difference between the two studies was 6.5 days (range: 5–8 days). Results: There was a significant difference in the detection of pulmonary and nonpulmonary sarcoidosis lesions between planar 67Ga citrate scans and 18F-FDG-PET images (<0.0021). A total of 64 lesions were detected with 67Ga citrate scans in the thorax and elsewhere with a mean of 2.6 lesions (4%) per patient, while 85 lesions were found with 18F-FDG-PET, with a mean of 3.5 lesions (4.1%) per patient. There was complete agreement between 18F-FDG and 67Ga citrate in thoracic manifestations in four (16.6%) patients, and in non-thoracic manifestations in five (20.8%) patients. The interobserver variability showed a kappa value of 0.79. Conclusion: 67Ga citrate and 18F-FDG are useful tracers for diagnostic evaluation of thoracic sarcoidosis. 18F-FDG seems to be more suitable for imaging the mediastinum, the bi-hilar lymph nodes, the posterior regions of the lungs and non-thoracic lesions. Further prospective studies are needed to clarify the role of both tracers in early diagnosis and staging of sarcoidosis, and to resolve questions concerning medical treatment and follow-up.

Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Karoline Spaepen ◽  
Sigrid Stroobants ◽  
Patrick Dupont ◽  
Peter Vandenberghe ◽  
Johan Maertens ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Prognostic Value ◽  
High Dose Chemotherapy ◽  
Emission Tomography ◽  
High Dose ◽  
Conventional Imaging ◽  
Positron Emission ◽  
Fdg Pet Scan ◽  
18F Fdg ◽  
Fluorine 18 Fluorodeoxyglucose

Abstract The study assessed the prognostic value of fluorine 18-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) after salvage chemotherapy before high-dose chemotherapy with stem cell transplantation (HDT/SCT) in patients with induction failure or relapsing chemosensitive lymphoma. Retrospective analysis of the clinical and conventional imaging data of 60 patients scheduled for HDT/SCT was performed in parallel with the analysis of the [18F]FDG-PET results. To determine the ability of [18F]FDG-PET to predict clinical outcome, PET images were reread without knowledge of conventional imaging and clinical history. Presence or absence of abnormal [18F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Thirty patients showed a negative [18F]FDG-PET scan before HDT/SCT; 25 of those remained in complete remission, with a median follow-up of 1510 days. Two patients died due to a treatment-related mortality but without evidence of recurrent disease at that time (228-462 days). Only 3 patients had a relapse (median PFS, 1083 days) after a negative [18F]FDG-PET scan. Persistent abnormal [18F]FDG uptake was seen in 30 patients and 26 progressed (median PFS, 402 days); of these 26, 16 died from progressive disease (median OS, 408 days). Four patients are still in complete remission after a positive scan. Comparison between groups indicated a statistically significant association between [18F]FDG-PET findings and PFS (P &lt; .000001) and OS (P &lt; .00002). [18F]FDG-PET has an important prognostic role in the pretransplantation evaluation of patients with lymphoma and enlarges the concept of chemosensitivity used to select patients for HDT/SCT. (Blood. 2003;102:53-59)

scholarly journals Pulmonary Findings of [18F]FDG PET/CT Images on Asymptomatic COVID-19 Patients

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 839
Author(s):  
Tzu-Chuan Ho ◽  
Chin-Chuan Chang ◽  
Hung-Pin Chan ◽  
Ying-Fong Huang ◽  
Yi-Ming Arthur Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Fdg Pet ◽  
Standardized Uptake Value ◽  
Fdg Uptake ◽  
Asymptomatic Patients ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg ◽  
Maximal Standardized Uptake Value ◽  
Fdg Pet Ct

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: “asymptomatic”, “COVID-19”, “[18F]FDG PET/CT”, and “nuclear medicine” were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.

scholarly journals Coronary, aortic and carotid artery inflammation by 18F-fluorodeoxyglucose positron emission tomography in acute and chronic coronary artery disease

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
W Nammas ◽  
S Uotila ◽  
J Teuho ◽  
M Pietila ◽  
J Airaksinen ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Fdg Pet ◽  
Carotid Arteries ◽  
Standardized Uptake Value ◽  
Chronic Coronary Artery Disease ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Arterial Inflammation ◽  
18F Fdg ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. Background 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can detect arterial inflammation in individuals with atherosclerosis, but the associations among different vascular territories for 18F-FDG uptake are not known. Purpose We explored any possible correlation between arterial inflammation quantified by 18F-FDG PET in the aorta, carotid arteries, and coronary arteries in patients presenting with acute coronary syndrome (ACS), or chronic coronary artery disease (CAD). Methods Prospectively, we performed hybrid computed tomography angiography and 18F-FDG PET in 43 patients (26 ACS and 17 chronic CAD) at 6.6 ± 5.7 days following invasive coronary angiography. 18F-FDG PET was performed 90 minutes after injection of 302.2 ± 28.4 MBq 18F-FDG. Arterial 18F-FDG uptake was measured in the thoracic aorta, carotid arteries, and coronary arteries, and expressed as the target-to-background ratio (TBR; the ratio between arterial maximal standardized uptake value normalized to blood pool mean standardized uptake value) in the whole artery, and in the most diseased segment (MDS). Results Mean age was 64.9 ± 9.1 years, 90.7% males. The whole artery 18F-FDG uptake was higher in the aorta than in the carotid arteries (median TBR 2.23, interquartile range [0.36] vs. 1.88 [0.42], p &lt; 0.001); whereas uptake in the coronary arteries was lower than in the aorta or carotid arteries (1.13 [0.23], p &lt; 0.001 both). Similarly, 18F-FDG uptake in the aortic MDS was higher than in the carotid MDS (2.75 [0.62] vs. 2.25 [0.63], p &lt; 0.001); whereas 18F-FDG uptake in the coronary MDS was the lowest (1.40 [0.33], p &lt; 0.001 both). These findings were consistent in both ACS and chronic CAD patients. The whole artery 18F-FDG uptake of the aorta and carotid arteries correlated in patients with ACS (r = 0.58, p = 0.002), but not in patients with chronic CAD (r = 0.21, p = 0.3). There was no correlation between the whole artery 18F-FDG uptake in the coronary arteries and either the aorta or carotid arteries in the whole cohort (r=-0.16, p = 0.2, r = 0.01, p = 0.9, respectively), in patients with ACS (r = 0.06, p = 0.7, r=-0.01, p = 0.9, respectively), or in those with chronic CAD (r=-0.4, p = 0.1, r=-0.09, p = 0.7, respectively). Conclusions In patients with ACS or chronic CAD, large arteries had higher 18F-FDG uptake than the coronary arteries. The intensity of 18F-FDG uptake in the coronary arteries did not correlate with that in the carotid arteries or the aorta, indicating that disease activity differs between large arteries and coronary arteries.

POSITRON EMISSION TOMOGRAPHY WITH 18F -FDG IN THE DIAGNOSIS OF PROSTHETIC HEART VALVE ENDOCARDITIS

2021 ◽  
Vol 5 (1) ◽  
pp. 1151-1160
Author(s):  
A.S. Lukashevich ◽  
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
Fdg Pet ◽  
Prosthetic Heart Valve ◽  
Emission Tomography ◽  
Whole Body ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Purpose. The purpose of the article is to evaluate the diagnostic significance of positron emission tomography / computed tomography with 18F -fluorodeoxyglucose (18F -FDG PET/CT) for the diagnosis of prosthetic endocarditis. Methods of research. The study included 82 patients with suspected prosthetic endocarditis in accordance with the criteria proposed by Duke University [1-5]. The patients received hospital treatment at the State Institution RSPC "Cardiology" from January 2016 to March 2021. The study was of a prospective, non-randomized, single-center cohort design. The duration of the monitor period was 12 months from the moment of patients’ inclusion in the study. Whole-body positron emission tomography / computed tomography (PET/CT) examinations were performed in 82 patients. 27 patients were selected for surgical treatment. Conservative treatment group included 16 patients. 27 patients were selected into the observation group, they were suspected to have prosthetic heart valve infection in the primary referral and underwent PET/CT scanning, according to which the diagnosis of prosthetic endocarditis was excluded. The event under the study did not develop in this group during the year of observation. Results and conclusion. The history of infective endocarditis was not statistically significant and did not increase the risk of developing prosthetic endocarditis in the sample presented. The Duke criteria are less reliable in establishing the diagnosis of prosthetic endocarditis. The median number of days from the date of the first prosthesis implantation to the onset of prosthetic endocarditis was about 4 years. This study revealed that the development of the infectious process in the area of the prosthesis was noted in a more distant postoperative period compared to literature data. Histological confirmation of infection was noted in 100% (27 patients) of cases in reoperated patients. The presence of a more formidable complication such as valve ring abscess located mainly in the projection of the aortic valve ring was quite common in both groups. Presepsin and Interleukin-6 have a statistically significant (U = 394,50 p = 0,01 and U = 94,50 p = 0.004) value in the prognosis of prosthetic endocarditis. Considering the data obtained from ROC analysis, it can be said that the cut-off point at which it is possible to diagnose prosthetic endocarditis based on PETCT is 2.85. The presented methods for the interpretation of whole-body FDG-PET/CT images of patients with suspected infectious complications after cardiac surgery, as well as with the presence of prosthetic endocarditis, show high sensitivity and specificity.

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