scholarly journals Positron Emission Tomography (PET) and Pharmacokinetics: Classical Blood Sampling Versus Image-Derived Analysis of [18F]FAZA and [18F]FDG in a Murine Tumor Bearing Model

2018 ◽  
Vol 21 (1s) ◽  
pp. 32s-47s ◽  
Author(s):  
Hans-Soenke Jans ◽  
Xiao-Hong Yang ◽  
Dion R Brocks ◽  
Piyush Kumar ◽  
Melinda Wuest ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Vena Cava ◽  
Blood Sampling ◽  
Tumor Uptake ◽  
Blood Samples ◽  
Non Invasive ◽  
Tumor Bearing ◽  
Positron Emission ◽  
18F Fdg ◽  
Derived Data

Purpose: Pharmacokinetic (PK) data are generally derived from blood samples withdrawn serially over a defined period after dosing. In small animals, blood sampling after dosing presents technical difficulties, particularly when short time intervals and frequent sampling are required. Positron emission tomography (PET) is a non-invasive functional imaging technique that can provide semi-quantitative temporal data for defined volume regions of interest (vROI), to support kinetic analyses in blood and other tissues. The application of preclinical small-animal PET to determine and compare PK parameters for [18F]FDG and [18F]FAZA, radiopharmaceuticals used clinically for assessing glucose metabolism and hypoxic fractions, respectively, in the same mammary EMT6 tumor-bearing mouse model, is reported here. Methods: Two study groups were used: normal BALB/c mice under isoflurane anesthesia were intravenously injected with either [18F]FDG or [18F]FAZA. For the first group, blood-sampling by tail artery puncture was used to collect blood samples which were then analyzed with Radio-microTLC. Dynamic PET experiments were performed with the second group of mice and analyzed for blood input function and tumor uptake utilizing a modified two compartment kinetic model. Heart and inferior vena cava vROIs were sampled to obtain image-derived data. PK parameters were calculated from blood samples and image-derived data. Time-activity curves (TACs) were also generated over regions of liver, kidney and urinary bladder to depict clearance profiles for each radiotracer. Results: PK values generated by classical blood sampling and PET image-derived analysis were comparable to each other for both radiotracers. Heart vROI data were suitable for analysis of [18F]FAZA kinetics, but metabolic uptake of radioactivity mandated the use of inferior vena cava vROIs for [18F]FDG analysis. While clearance (CL) and blood half-life (t½) were similar for both [18F]FDG and [18F]FAZA for both sampling methods, volume of distribution yielded larger differences, indicative of limitations such as partial volume effects within quantitative image-derived data. [18F]FDG underwent faster blood clearance and had a shorter blood half-life than [18F]FAZA. Kinetic analysis of tumor uptake from PET image data showed higher uptake and longer tumor tissue retention of [18F]FDG, indicative of the tumor’s glucose metabolism rate, versus lower tumor uptake and retention of [18F]FAZA. While [18F]FAZA possesses a somewhat greater hepatobiliary clearance , [18F]FDG clears faster through the renal system which results in faster radioactivity accumulation in the urinary bladder. Conclusions: The present study provides a working example of the applicability of functional PET imaging as a suitable tool to determine PK parameters in small animals. The comparative analysis in the current study demonstrates that it is feasible to use [18F]FDG PET and [18F]FAZA PET in the same model to analyze their blood PK parameters, and to estimate kinetic parameters for these tracers in tumor. This non-invasive imaging-based determination of tissue kinetic parameters facilitates translation from pre-clinical to clinical phases of drug development. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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.

Influence of feeding regimens on non-invasive inferior vena cava and hepatic vein velocity measurements in infants

2007 ◽  
Vol 89 (8) ◽  
pp. 929-932
Author(s):  
Z Kurugöl ◽  
R Özyürek ◽  
C Dorak ◽  
E Levent ◽  
A Egemen ◽  
...  
Keyword(s):  
Inferior Vena Cava ◽  
Hepatic Vein ◽  
Inferior Vena ◽  
Vena Cava ◽  
Velocity Measurements ◽  
Non Invasive

scholarly journals Inferior Vena Cava Collapsibility Index: A Precise Non-invasive Tool for Evaluation of Edema in Children with Nephrotic Syndrome.

2021 ◽  
Author(s):  
Hanan El-Halaby ◽  
Ashraf Bakr ◽  
Mohamed El-Assmy ◽  
Hussein Abdelaziz Abdalla ◽  
Marwa Salem ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Inferior Vena Cava ◽  
Inferior Vena ◽  
Vena Cava ◽  
Fractional Excretion ◽  
Volume Status ◽  
Non Invasive ◽  
Collapsibility Index ◽  
Fractional Excretion Of Sodium ◽  
Status Assessment

Abstract Evaluating the volume status in children with Idiopathic nephrotic syndrome (INS) is mandatory to guide treatment and avoid unnecessary possibly hazardous albumin use. This study aimed to evaluate and compare the available tools used for volume status assessment and differentiating type of edema in children with INS. Sixty children with active INS were included and subdivided into hypovolemic and non-hypovolemic groups based on fractional excretion of sodium (FeNa%) and clinical assessment. All patients were studied for Inferior vena cava collapsibility index (IVCCI), plasma atrial natriuretic peptide (ANP) concentration and Body composition monitor (BCM). Forty-four patients (77.3%) had non-hypovolemic and 16 (26.7%) had hypovolemic states. Plasma ANP levels didn’t differ between hypovolemic and non-hypovolemic subgroups. IVCCI was higher in hypovolemic group (p<0.001) with sensitivity 87.5% and specificity 81.8% for hypovolemia detection while BCM-over hydration (BCM-OH) values were higher in non-hypovolemic group (p=0.04) with sensitivity= 68.2% and specificity =75% for detection of hypervolemia. FeNa% showed negative significant correlation with IVCCI (r= -0.578, p <0.001) and positive significant correlation with BCM-OH (r= 0.33, p=0.018), while FeNa% showed non-significant correlation to plasma ANP concentration (p=0.25). Conclusion: Non-hypovolemic edema is more frequent in edematous INS children than hypovolemic states. IVCCI is a reliable non-invasive bedside tool for evaluating volume status in INS children and is superior to BCM while plasma ANP levels can’t discriminate type of edema in INS.

Complexing of Low Mr-Weight Human Urokinase In Rat Serum And Its Degradation Into Fragments Of Very Small Molecular Weight In Vivo But Not In Vitro

1981 ◽  
Author(s):  
Ph Schneider ◽  
M Ruegg ◽  
F Bachmann
Keyword(s):  
Molecular Weight ◽  
Inferior Vena ◽  
Vena Cava ◽  
Albino Rats ◽  
Small Molecular Weight ◽  
Rat Serum ◽  
Blood Samples ◽  
Sds Page

Highly purified lew molecular weight urokinase (LMR-UK), moving on SDS-PAGE (reduced and nan-reduced) as a single band of 32 kdalton, was labelled with 125I by the chlora- mine-T method. 106 cpn of this 125I-LMr-UK (94% TCA preci- pitable) were injected into the inferior vena cava of la- par atomized albino rats, which were maintained at 37°C. Blood samples were collected by cardiac puncture 5, 30 and 90 min respectively after the injection. Serun, obtained from these samples, was fractionated on a Sephadex G-100 column, calibrated with proteins of known Mr. Radioactivity was measured in the collected fractions.In the 5 min sample, the radioactivity was distributed in 2 peaks, corresponding to 32 kdalton and to < 70 kdalton respectively. In the 30 min sample, the distribution was characterized by a diminution of the 32 kdalton peak and the appearance of a third peak corresponding to a Mr of < 4 kdalton. In the 90 min sample, the LMr-UK peak had disappeared almost completely. About 40% of the 125I-activity was present in a skewed high Mr peak with a broad maximum in the 85-100 kdalton region; ≥ 60% of the 125I-activity was recovered in late fractions corresponding to < 4 kdalton. In control experiments, pooled rat serum was incubated in vitro with 125I-LMr-UK for 5, 30 and 90 min respectively and samples were fractionated on the same column. The radioactivity distribution shewed only the 32 and > 70 kdalton peaks, but no < 4 kdalton peak.These results suggest that LMr-UK is complexed to a carrier protein, both in vivo and in vitro, but that it is degraded into small fragments in vivo only. Attempts to characterize the nature of these complexes are in progress.

Utility of Molecular Imaging with 2-Deoxy-2-[Fluorine-18] Fluoro-D-Glucose Positron Emission Tomography (18F-FDG PET) for Small Cell Lung Cancer (SCLC): A Radiation Oncology Perspective

2019 ◽  
Vol 12 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Omer Sager ◽  
Ferrat Dincoglan ◽  
Selcuk Demiral ◽  
Bora Uysal ◽  
Hakan Gamsiz ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Radiation Oncology ◽  
Imaging Modality ◽  
Small Cell ◽  
Emission Tomography ◽  
Small Cell Lung ◽  
Non Invasive ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg

Background and Objective: Although accounting for a relatively small proportion of all lung cancers, small cell lung cancer (SCLC) remains to be a global health concern with grim prognosis. Radiotherapy (RT) plays a central role in SCLC management either as a curative or palliative therapeutic strategy. There has been considerable progress in RT of SCLC, thanks to improved imaging techniques leading to accurate target localization for precise delivery of RT. Positron emission tomography (PET) is increasingly used in oncology practice as a non-invasive molecular imaging modality. Methods: Herein, we review the utility of molecular imaging with 2-deoxy-2-[fluorine-18] fluoro-Dglucose PET (18F-FDG PET) for SCLC from a radiation oncology perspective. Results: There has been extensive research on the utility of PET for SCLC in terms of improved staging, restaging, treatment designation, patient selection for curative/palliative intent, target localization, response assessment, detection of residual/recurrent disease, and prediction of treatment outcomes. Conclusion: PET provides useful functional information as a non-invasive molecular imaging modality and may be exploited to improve the management of patients with SCLC. Incorporation of PET/CT in staging of patients with SCLC may aid in optimal treatment allocation for an improved therapeutic ratio. From a radiation oncology perspective, combination of functional and anatomical data provided by integrated PET/CT improves discrimination between atelectasis and tumor, and assists in the designation of RT portals with its high accuracy to detect intrathoracic tumor and nodal disease. Utility of molecular imaging for SCLC should be further investigated in prospective randomized trials to acquire a higher level of evidence for future potential applications of PET.

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