Imaging biomarkers of oedema and fibrosis in a rat

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Imaging biomarkers of oedema and fibrosis in a rat model of Drug-Induced Interstitial Lung Disease (DIILD) (Conference Abstract)

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Conference Abstract: Imaging of DIILD in rats

Imaging biomarkers of oedema and fibrosis in a rat model of Drug-Induced Interstitial Lung Disease (DIILD) (Conference Abstract)

Irma Mahmutovic Persson, Anders Örbom, Per-Ola Önnervik, Karin von Wachenfeldt and Lars E. Olsson- on behalf of the TRISTAN Consortium


European Respiratory Society, International Congress 2018, 15-19 Septembr 2018, Paris, France

 

Background

Drugs used to treat various diseases may induce lung injury known as drug induced interstitial lung disease (DIILD). Clinical and pre-clinical studies within the TRISTAN-consortium are aimed at finding translational Imaging Biomarkers (IB) that can indicate progression of DIILD at an early stage. In the present in vivo study, magnetic resonance imaging (MRI) was applied along with analyses of lavage and lung tissue.

CONFERENCE ABSTRACT: IMAGING OF DIILD IN RATS
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Slow infusion improves precision of liver function

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Slow infusion improves precision of liver function measurements by DCE-MRI (Conference Abstract)

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Conference Abstract: Slow infusion dce-mri

Slow infusion improves precision of liver function measurements by DCE-MRI (Conference Abstract)

Sirisha Tadimalla and Steven Sourbron


The British Chapter of ISMRM Annual Meeting, 24-26 September 2018, Somerville College, Oxford

 

Background

Quantitative dynamic contrast-enhanced (DCE) MRI with a rapidly injected bolus of gadoxetate can be used to quantify liver perfusion and transporter function [1,2]. Measuring these rapid changes requires high temporal resolution, and this involves compromises in spatial resolution, coverage or SNR. However, when the aim is to measure hepatocellular function (a slow process), rather than perfusion (a fast process), there is no rationale for a rapid injection.

CONFERENCE ABSTRACT: SLOW INFUSION DCE-MRI
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Accuracy, repeatability, and reproducibility of R1

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Accuracy, repeatability, and reproducibility of R1 in 12 small-animal MRI systems (Conference Abstract)

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Conference Abstract: Phantom R1 Repeabililty

Accuracy, repeatability, and reproducibility of R1 in 12 small-animal MRI systems (Conference Abstract)

JC Waterton, CDG Hines, PD Hockings, I Laitinen, S Ziemian, S Campbell, M Gottschalk, C Green, M Haase, K Hoffmann, H-P Juretschke, S Koehler, W Lloyd, Y Luo, I Mahmutovic Persson, JPB O Connor, LE Olsson, GJM Parker, K Pindoriah, JE Schneider, D Steinmann, K Strobel, I Teh, A Veltien, X Zhang, G Schuetz


British Chapter ISMRM Annual Meeting 24th-26th September 2018, Oxford, UK Poster Abstract PO-19


Background:  Many translational MR biomarkers derive from measurements of the longitudinal relaxation rate R1, but evidence for between-site reproducibility of R1 in small-animal MRI is lacking.  Objective: To assess R1 repeatability and multi-site reproducibility in phantoms for preclinical MRI. Methods: R1 was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1-13 days.  R1 was analysed in three different regions of interest, giving 360 measurements in total.  Root-mean-square repeatability and reproducibility coefficients of variation were calculated.  Relaxivities were calculated.  Results: Day-to-day repeatability (N=180 regions of interest) was 2.3%.  Between-centre reproducibility (N=9 centres) was 1.4%.  The relaxivity of aqueous Ni2+ in 2% agarose varied between 0.66 s-1mM-1 at 3T and 0.94 s-1mM-1 at 11.7T.

CONFERENCE ABSTRACT: PHANTOM R1 REPEABILILTY
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In vitro and in vivo evaluation of novel 89Zr-chelators

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In vitro and in vivo evaluation of novel 89Zr-chelators (Conference Abstract)

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Conference Abstract: 89Zr chelate evaluation

In vitro and in vivo evaluation of novel 89Zr-chelators (Conference Abstract)

Rene Raave, Gerwin Sandker, Sandra Heskamp, Otto Boerman, Mark Rijpkema, Floriane Mangin, Michel Meyer, Jean-Claude Chambron, Mathieu Moreau, Claire Bernhard, Adrien Dubois, Laurene Da Costa, Victor Goncalves, Franck Denat


Third international edition of the symposium on Technetium and Other Radiometals in Chemistry and Medicine (TERACHEM 2018), September 26-29, 2018, Bressanone (BZ), Italy

Abstract

The current “gold standard” chelator to label antibodies with 89Zr for immunoPET is desferrioxamine (DFO).1 Preclinical studies have shown that the 89Zr-DFO complex is partly unstable in vivo, resulting in release of 89Zr and subsequent accumulation in mineral bone. This bone uptake may prevent the detection of bone metastases, and hampers accurate estimation of the radiation dose to the bone marrow in dose planning for radioimmunotherapy. Therefore, there is a need for more stable 89Zr chelators.

CONFERENCE ABSTRACT: 89ZR CHELATE EVALUATION
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Development and evaluation of a new Interleukin

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Development and evaluation of a new Interleukin-2 PET radioligand Al[18F]RESCA-IL2: comparison with [18F]FB-IL2 (Conference Abstract)

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Conference Abstract: IL-2 PET

Development and evaluation of a new Interleukin-2 PET radioligand Al[18F]RESCA-IL2: comparison with [18F]FB-IL2 (Conference Abstract)

I.F. Antunes, E.L. van der Veen, E.E.M. Deneer, F. Cleeren, G. Bormans, P.H Elsinga, R.A.J.O. Dierckx, E.G.E de Vries, E.F.J. de Vries


31st Annual Congress of the European Association of Nuclear Medicine, 13-17 October 2018, Düsseldorf

 

Aim

Interleukin-2 is a 15.5 kDa glycoprotein that binds with high affinity to IL2 receptors (IL2R) that are overexpressed on activated T-cells, which are involved in various pathological diseases, such as autoimmune diseases, but also play a major role in the tumor immune response. We have developed 18F-FB-IL2 which has been successfully used for detecting activated T-cells in rodents [1]. Recently, a GMP-compliant production of 18F-FB-IL2 for clinical use was implemented, but the production method proved to be complex and time-consuming. Therefore, we now developed a simplified method to label IL2 with 18F. Here we present the synthesis of Al 18F-RESCA-IL2 and its comparison to 18F-FB-IL2.

CONFERENCE ABSTRACT: IL-2 PET
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Evaluation of the in vitro and in vivo characteristics

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Evaluation of the in vitro and in vivo characteristics of the novel89Zr-octacoordinated chelator DFO-cyclo* compared to the hexacoordinated DFO (Conference Abstract)

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Conference Abstract: Novel 89Zr chelator

Evaluation of the in vitro and in vivo characteristics of the novel89Zr-octacoordinated chelator DFO-cyclo* compared to the hexacoordinated DFO (Conference Abstract)

Rene Raave, Gerwin Sandker, Sandra Heskamp, Otto Boerman, Mark Rijpkema, Floriane Mangin, Michel Meyer, Jean-Claude Chambron, Mathieu Moreau, Claire Bernhard, Victor Goncalves, Franck Denat


31st Annual Congress of the European Association of Nuclear Medicine, 13-17 October 2018, Duesseldorf

Abstract

The current “gold standard” chelator to label antibodies with 89Zr for immunoPET is desferrioxamine (DFO). Preclinical studies have shown that the 89Zr-DFO complex is partly unstable in vivo, resulting in release of 89Zr and subsequent accumulation in mineral bone tissue. This bone uptake may prevent the detection of bone metastases, and hampers accurate estimation of the radiation dose to the bone marrow in dose planning for radioimmunotherapy. Therefore, there is a need for a more stable 89Zr chelator. Here we report DFO-cyclo*, a preorganized extended DFO derivative introducing an octacoordination, and investigate the stability of its 89Zrr complex over the unsaturated hexacoordinated 89Zr-DFO complex in vitro and in vivo.

CONFERENCE ABSTRACT: NOVEL 89ZR CHELATOR
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Drug-Induced Interstitial Lung Disease: A Systematic Review

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Drug-Induced Interstitial Lung Disease: A Systematic Review

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DIILD Review

Drug-Induced Interstitial Lung Disease: A Systematic Review

Sarah Skeoch, Nicholas Weatherley , Andrew J. Swift, Alexander Oldroyd, Christopher Johns, Conal Hayton, Alessandro Giollo, James M. Wild, John C. Waterton, Maya Buch, Kim Linton, Ian N. Bruce, Colm Leonard, Stephen Bianchi and Nazia Chaudhuri


J. Clin. Med. 2018, 7(10), 356 doi: 10.3390/jcm7100356.

 

Background

Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents. Methods: In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on DIILD. Results: Following a quality assessment, 156 full-text papers describing more than 6000 DIILD cases were included in the review. However, the majority of the papers were of low or very low quality in relation to the review question (78%). Thus, it was not possible to perform a meta-analysis, and descriptive review was undertaken instead. DIILD incidence rates varied between 4.1 and 12.4 cases/million/year. DIILD accounted for 3–5% of prevalent ILD cases. Cancer drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The radiopathological phenotype of DIILD varied between and within agents, and no typical radiological pattern specific to DIILD was identified. Mortality rates of over 50% were reported in some studies. Severity at presentation was the most reliable predictor of mortality. Glucocorticoids (GCs) were commonly used to treat DIILD, but no prospective studies examined their effect on outcome. Conclusions: Overall high-quality evidence in DIILD is lacking, and the current review will inform larger prospective studies to investigate the diagnosis and management of DIILD.

DIILD REVIEW
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Feasibility of PET/CT system performance harmonisation

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Feasibility of PET/CT system performance harmonisation for quantitative multicentre 89Zr studies

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PET/CT Harmonization for Multicenter Studies

Feasibility of PET/CT system performance harmonisation for quantitative multicentre 89Zr studies

Andres Kaalep, Marc Huisman, Terez Sera, Danielle Vugts, Ronald Boellaard, on behalf of EARL, EATRIS and the TRISTAN Consortium


EJNMMI Physics 2018 (5):26 doi: 10.1186/s40658-018-0226-7.

 

Purpose

The aim of this study was to investigate the variability in quantitative performance and feasibility of quantitative harmonisation in 89Zr PET/CT imaging.

Methods

Eight EANM EARL-accredited (Kaalep A et al., Eur J Nucl Med Mol Imaging 45:412-22, 2018) PET/CT systems were investigated using phantom acquisitions of uniform and NEMA NU2-2007 body phantoms. The phantoms were filled according to EANM EARL guidelines for 18F-FDG, but 18F-FDG solution was replaced by a 89Zr calibration mixture. For each system, standard uptake value (SUV) accuracy and recovery coefficients (RC) using SUVmean, SUVmax and SUVpeak metrics were determined.

Results

All eight investigated systems demonstrated similarly shaped RC curves, and five of them exhibited closely aligning recoveries when SUV bias correction was applied. From the evaluated metrics, SUVpeak was found to be least sensitive to noise and reconstruction differences among different systems.

Conclusions

Harmonisation of PET/CT scanners for quantitative 89Zr studies is feasible when proper scanner-dose calibrator cross-calibration and harmonised image reconstruction procedures are followed. An accreditation programme for PET/CT scanners would facilitate multicentre 89Zr quantitative studies.

PET/CT HARMONIZATION FOR MULTICENTER STUDIES
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Integrating molecular nuclear imaging in clinical research

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Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

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Review: PET to improve anti-cancer therapy

Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

Elisabeth G. E. de Vries, Laura Kist de Ruijter, Marjolijn N. Lub-de Hooge, Rudi A. Dierckx, Sjoerd G. Elias & Sjoukje F. Oosting


Nature Reviews Clinical Oncology (2018); doi: 10.1038/s41571-018-0123-y.

Abstract

Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug–target engagement and responses to treatment. This integrative approach could therefore streamline biomarker and drug development, although a range of issues need to be overcome in order to enable a broader use of molecular imaging in clinical trials. In this Perspective article, we outline the multistage process of developing novel molecular imaging biomarkers. We discuss the challenges that have restricted the use of molecular imaging in clinical oncology research to date and outline future opportunities in this area.

REVIEW: PET TO IMPROVE ANTI-CANCER THERAPY
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Accuracy, repeatability, and reproducibility of R1 in 12

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Accuracy, repeatability, and reproducibility of R1 in 12 small-animal MRI systems (Conference Abstract)

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Conference Abstract: Accuracy of R1 determination

Accuracy, repeatability, and reproducibility of R1 in 12 small-animal MRI systems (Conference Abstract)

Waterton JC, Hines CDG, Hockings PD, Laitinen I, Ziemian S, Campbell S, Gottschalk M, Green C, Haase M, Hoffmann K, Juretschke H-P, Koehler S, Lloyd W, Y Luo Y, Mahmutovic Persson I, O’Connor JPB, Olsson LE, Parker GJM, Pindoria K, Schneider JE, Steinmann D, Strobel K, Teh I, Veltien A, Zhang X, Schütz G


Proceedings of the International Society of Magnetic Resonance in Medicine 27th Scientific Meeting and Exhibition, Montréal, Canada 11th-16th May 2019

 

CONFERENCE ABSTRACT: ACCURACY OF R1 DETERMINATION
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