Evaluation of PET quantification accuracy in vivo

2014 ◽  
Vol 53 (03) ◽  
pp. 67-77 ◽  
Author(s):  
F. Hofheinz ◽  
G. Schramm ◽  
L. Oehme ◽  
B. Beuthien-Baumann ◽  
M. Lukas ◽  
...  
Keyword(s):  
Activity Concentration ◽  
Urine Samples ◽  
Whole Body ◽  
In Vivo Evaluation ◽  
Positron Emission ◽  
Quantitative Accuracy ◽  
Pet Ct ◽  
Quantification Accuracy ◽  
Well Counter

SummaryQuantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. Aim: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. Patients, methods: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: n = 19). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined. Results: Activity concentration in the bladder (PET) was systematically lower than in the urine samples (well The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. Conclusions: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.

scholarly journals 89Zr-Labeled AR20.5: A MUC1-Targeting ImmunoPET Probe

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2315 ◽  
Author(s):  
Kimberly Fung ◽  
Delphine Vivier ◽  
Outi Keinänen ◽  
Elaheh Khozeimeh Sarbisheh ◽  
Eric W. Price ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Tissue ◽  
Activity Concentration ◽  
Poor Response ◽  
Response To Therapy ◽  
In Vivo Evaluation ◽  
In Vivo Experiments ◽  
Positron Emission ◽  
Tumor Types

High expression levels of the tumor-associated antigen MUC1 have been correlated with tumor aggressiveness, poor response to therapy, and poor survival in several tumor types, including breast, pancreatic, and epithelial ovarian cancer. Herein, we report the synthesis, characterization, and in vivo evaluation of a novel radioimmunoconjugate for the immuno-positron emission tomography (immunoPET) imaging of MUC1 expression based on the AR20.5 antibody. To this end, we modified AR20.5 with the chelator desferrioxamine (DFO) and labeled it with the positron-emitting radiometal zirconium-89 (t1/2 ~3.3 d) to produce [89Zr]Zr-DFO-AR20.5. In subsequent in vivo experiments in athymic nude mice bearing subcutaneous MUC1-expressing ovarian cancer xenografts, [89Zr]Zr-DFO-AR20.5 clearly delineated tumor tissue, producing a tumoral activity concentration of 19.1 ± 6.4 percent injected dose per gram (%ID/g) at 120 h post-injection and a tumor-to-muscle activity concentration ratio of 42.4 ± 10.6 at the same time point. Additional PET imaging experiments in mice bearing orthotopic MUC1-expressing ovarian cancer xenografts likewise demonstrated that [89Zr]Zr-DFO-AR20.5 enables the visualization of tumor tissue—including metastatic lesions—with promising tumor-to-background contrast.

scholarly journals Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64–labeled daratumumab

2020 ◽  
Vol 4 (20) ◽  
pp. 5194-5202
Author(s):  
Amrita Krishnan ◽  
Vikram Adhikarla ◽  
Erasmus K. Poku ◽  
Joycelynne Palmer ◽  
Ammar Chaudhry ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity And Specificity ◽  
Imaging Techniques ◽  
Phase 1 ◽  
Whole Body ◽  
Human Antibody ◽  
Whole Body Imaging ◽  
Positron Emission ◽  
Pet Ct

Abstract 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.

scholarly journals Development of [18F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide

2019 ◽  
Vol 18 ◽  
pp. 153601211985218 ◽  
Author(s):  
Wojciech G. Lesniak ◽  
Ronnie C. Mease ◽  
Samit Chatterjee ◽  
Dhiraj Kumar ◽  
Ala Lisok ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Whole Body ◽  
In Vivo Evaluation ◽  
Positron Emission ◽  
Comprehensive Picture ◽  
Specific Uptake ◽  
Ex Vivo Biodistribution

Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with [18F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, 19FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC50], 26-32 nM). The radiotracer, [18F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[18F]fluoronicotinate ([18F]FPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of [18F]FPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of [18F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [18F]FPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer.

scholarly journals Influence of patient motion on quantitative accuracy in cardiac 15O-water positron emission tomography

2021 ◽  
Author(s):  
Jonny Nordström ◽  
Hendrik J. Harms ◽  
Tanja Kero ◽  
Jens Sörensen ◽  
Mark Lubberink
Keyword(s):  
Motion Detection ◽  
Detection Algorithm ◽  
Clinical Effects ◽  
Average Deviation ◽  
Patient Motion ◽  
Motion Data ◽  
Positron Emission ◽  
Quantitative Accuracy ◽  
Pet Ct ◽  
Using Data

Abstract Background Patient motion is a common problem during cardiac PET. The purpose of the present study was to investigate to what extent motions influence the quantitative accuracy of cardiac 15O-water PET/CT and to develop a method for automated motion detection. Method Frequency and magnitude of motion was assessed visually using data from 50 clinical 15O-water PET/CT scans. Simulations of 4 types of motions with amplitude of 5 to 20 mm were performed based on data from 10 scans. An automated motion detection algorithm was evaluated on clinical and simulated motion data. MBF and PTF of all simulated scans were compared to the original scan used as reference. Results Patient motion was detected in 68% of clinical cases by visual inspection. All observed motions were small with amplitudes less than half the LV wall thickness. A clear pattern of motion influence was seen in the simulations with a decrease of myocardial blood flow (MBF) in the region of myocardium to where the motion was directed. The perfusable tissue fraction (PTF) trended in the opposite direction. Global absolute average deviation of MBF was 3.1% ± 1.8% and 7.3% ± 6.3% for motions with maximum amplitudes of 5 and 20 mm, respectively. Automated motion detection showed a sensitivity of 90% for simulated motions ≥ 10 mm but struggled with the smaller (≤ 5 mm) simulated (sensitivity 45%) and clinical motions (accuracy 48%). Conclusion Patient motion can impair the quantitative accuracy of MBF. However, at typically occurring levels of patient motion, effects are similar to or only slightly larger than inter-observer variability, and downstream clinical effects are likely negligible.

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.

scholarly journals Development of [11C]erlotinib Positron Emission Tomography for In Vivo Evaluation of EGF Receptor Mutational Status

2012 ◽  
Vol 19 (1) ◽  
pp. 183-193 ◽  
Author(s):  
Idris Bahce ◽  
Egbert F. Smit ◽  
Mark Lubberink ◽  
Astrid A. M. van der Veldt ◽  
Maqsood Yaqub ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Egf Receptor ◽  
Emission Tomography ◽  
In Vivo Evaluation ◽  
Mutational Status ◽  
Positron Emission

Imaging Enterobacterales infections in patients using pathogen-specific positron emission tomography

2021 ◽  
Vol 13 (589) ◽  
pp. eabe9805
Author(s):  
Alvaro A. Ordonez ◽  
Luz M. Wintaco ◽  
Filipa Mota ◽  
Andres F. Restrepo ◽  
Camilo A. Ruiz-Bedoya ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Solid Phase ◽  
Multidrug Resistant ◽  
Sterile Inflammation ◽  
Emission Tomography ◽  
Whole Body ◽  
Hamster Model ◽  
Positron Emission ◽  
Pet Ct

Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use 18F-FDS from commercially available 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) at room temperature. In a hamster model, 18F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary Klebsiella pneumoniae pneumonia—a leading cause of complications in hospitalized patients with COVID-19. These data support 18F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.

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.

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