Scientific Highlights

European Society for Molecular Imaging - ESMI

The ESMI represents and advocates IMAGING SCIENCE

The ESMI is providing an international, interdisciplinary platform for knowledge exchange in the field covering basic sciences, translational aspects as well as clinical applications.

The ESMI is an academic, science-driven, independent, non-profit, and apolitical society, which promotes innovation, development, and applications of Imaging Sciences.

The ESMI is committed to scientific and technical excellence, to innovation and scientific quality, to the promotion of knowledge and understanding, and to interdisciplinary co-operation.

 


Figure: PET images of inflamed (A) and healthy (B) lungs of mice injected with 18F-AzaFol, which accumulates in folate receptor expressing macrophages.

The Center for Radiopharmaceutical Sciences (CRS) focuses on the development of new radiopharmaceuticals for positron emission tomography (PET) and other applications in nuclear medicine. Researchers at CRS have previously developed an 18F-based PET tracer (18F-AzaFol) for targeting the folate receptor, which is expressed on tumor cells, but also on activated macrophages involved in inflammatory processes. In a recent clinical study, 18F-AzaFol was investigated regarding its in vivo properties for folate-receptor targeting and assessed with respect to its safety profile in patients (NCT03242993).

In an interdisciplinary project of PSI and the University Hospital Zurich, preclinical studies were performed to demonstrate the potential of 18F-AzaFol for imaging macrophages in lung inflammation. 18F-AzaFol was shown to accumulate specifically in diseased lung tissue but not in lungs of healthy mice. The increased abundance of folate receptor-expressing macrophages was confirmed on diseased murine and human lung tissue using several in vitro methods (Schniering et al, 2019 Front Immunol).

Alveolar macrophages play an important role during coronavirus infections and replication and are involved in antiviral response and defense mechanisms. Most importantly, acute respiratory distress syndrome, a complication that develops in approximately 20% of patients, results from exuberant host inflammatory responses with macrophages as key players. 18F-AzaFol/PET based macrophage imaging may thus, be useful to investigate the complex immune response to COVID-19 infection and possibly enable the development of personalized treatment regimens in the future.

In this context, also other targets may be of interest for nuclear imaging. Recently, it was suggested that integrin may act as an alternative receptor for SARS-CoV-2 and could be implicated in its transmission and pathology. Clinically used RGD radiopharmaceuticals for integrin targeting may, therefore, be considered as effective imaging tools. In a proof-of-concept study, increased accumulation of an RGD radiopharmaceutical was demonstrated in a preclinical setting of lung inflammation by the same research team (Schniering et al. 2018 Ann Rheum Dis).


Schniering J., Benešová M., Brunner M., Haller S., Cohrs S., Frauenfelder T., Vrugt B., Feghali-Bostwick C.A., Schibli R., Distler O., Müller C., Maurer B. F-AzaFol for detection of folate receptor-β positive macrophages in experimental interstitial lung disease—A proof-of-concept study. Front Immunol (2019).
https://doi.org/10.3389/fimmu.2019.02724

 

Schniering J., Benešová M., Brunner M., Haller S., Cohrs S., Frauenfelder T., Vrugt B., Feghali-Bostwick C.A., Schibli R., Distler O., Müller C., Maurer B. Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2 Ann Rheum Dis (2018).
https://doi.org/10.1136/annrheumdis-2018-214322

 

 


PD Dr. Cristina Müller gibt Auskunft über neue Behandlungsmöglichkeiten für Patienten mit metastasiertem Prostatakrebs

 

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PD Dr. Cristina Müller won the lecture award for the presentation of her work entitled "161Tb-based Prostate Cancer Therapy: Investigating the "177Lu-PLUS Effect"


PSI and araris: So far, the active substances of certain cancer medications have been chemically attached to antibodies in order to eradicate the tumor cells. However, efficiency and tolerability were often rather poor. With a biological catalyst, the active ingredients can now be coupled site-specific and stoichiometric to an antibody. The in vivo characteristics of such immune conjugates are better than those of chemically manufactured analogues. If a radioactive molecule is attached at the same time, the antibody drug conjugate can be monitored in the body.


Dr. Janine Schniering performed her thesis (entitled “Towards Precision Medicine in Systemic Sclerosis - Exploration of Novel Imaging Tools for Interstitial Lung Disease”) at the Paul Scherrer Institute (PSI) under the supervision of Prof. Dr. Roger Schibli and at the University Hospital Zurich (USZ) under the supervision of PD. Dr. Britta Maurer and Prof. Oliver Distler. Her work describes a multi-​modal imaging approach across the scale (from cell to mouse to human) to exploit potential biomarkers and targets for the treatment and management of interstitial lung disease (ILD). ILD comprises a group of heterogeneous parenchymal lung disorders with high mortality, hard to specify diagnosis and difficult to manage treatment.


The Third International Symposium on Technesium and Other Radiometals in Chemistry and Medicine.

You are invited to attend the third international edition of the symposium on Technetium and Other Radiometals in Chemistry and Medicine (TERACHEM 2018), September 26-29, 2018 in Bressanone, Italy, which continues the long tradition of the previous symposia on Technetium and Rhenium in Chemistry and Nuclear Medicine. As a unique trait, the TERACHEM Symposium focuses on recent advances in radiometal coordination chemistry, and on new applications of radiometal-containing molecules in pre-clinical and clinical imaging and radiotherapy.
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For outstanding scientific work presented at the 31st Annual Congress of the European Association of Nuclear Medicine the Marie Curie Fund of the EANM herewith bestows the MARIE CURIE AWARD to Cristina Müller.
Ms. Müller received the award for the best research paper presented at the EANM Congress in 2018. The presentation was entitled:
"Terbium-161 for PMSA Targeted-Radionuclide Therapy of Prostate Cancer"
C. Mueller, C.A. Umbricht, N. Gracheva, V.J. Tschan, G. Pellegrini, P. Bernhardt, J.R. Zeevart, U. Koester, R. Schibli, N.P. van der Meulen


BEST PAPER 2018 - EJNMMI RESEARCH: "44Sc-PSMA-617 for radiotheragnostics in tandem with 177Lu-PSMA-617—preclinical investigations in comparison with 68Ga-PSMA-11 and 68Ga-PSMA-617"

A preclinical investigation of 44Sc-PSMA-617 for its use as a diagnostic match to 177Lu-PSMA-617. Findings demonstrated greater similarities for the in vitro characteristics and in vivo kinetics of 44Sc-PSMA-617 to 177Lu-PSMA-617 than 68Ga-PSMA-617 and 68Ga-PSMA-11.

Congratulations to the authors: Christoph A. Umbricht, Martina Benešová, Raffaella M. Schmid, Andreas Türler, Roger Schibli, Nicholas P. van der Meulen and Cristina Müller!
https://doi.org/10.1186/s13550-017-0257-4

and

BEST PAPER 2018 - EJNMMI RADIOPHARMACY AND CHEMISTRY:
"47Sc as useful β–-emitter for the radiotheragnostic paradigm: a comparative study of feasible production routes"

A comparison between two methods of 47Sc production, based on the neutron irradiation of enriched 46Ca and 47Ti targets. The 46Ca(n,γ)47Ca nuclear reaction provided higher quantities of a radionuclidically pure product, demonstrating a significant advantage over the 47Ti production method.

Congratulations to the authors: Katharina A. Domnanich, Cristina Müller, Martina Benešová, Rugard Dressler, Stephanie Haller, Ulli Köster, Bernard Ponsard, Roger Schibli, Andreas Türler and Nicholas P. van der Meulen!
https://doi.org/10.1186/s41181-017-0024-x


The Doktorandentag gives second- or third-year PhD students of the Institute of Pharmaceutical Sciences or associated institutions the opportunity to present their research projects. Mr. Umbricht presented his work entitled "Preclinical development of novel PSMA-targeting radioligands - modulation of albumin-binding properties to improve prostate cancer therapy".
 


Araris Biotech which is currently in foundation from the Center for Radiopharmaceutical Sciences (CRS, Prof. Roger Schibli) of BIO at PSI, has been ranked TOP 5 in the business plan competition of venture. The spin-off will be focused on the development of antibody-drug conjugates (ADCs) having a well-defined and optimal antibody-to-drug ratio. The technology will be used to establish a drug development platform for targeted therapies and diagnostic applications.
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Video presentation of Araris Biotech
 


The award has been attributed for an excellent oral presentation entitled "Albumin-binding PSMA radioligands – optimization of the tissue distribution profile".

 


The Neuroendocrine Tumor Research Foundation (NETRF) is committed to funding the most promising research in order to discover cures and more effective treatments for carcinoid, pancreatic, and related neuroendocrine cancers. In January 2018 the Board of Directors has awarded a Petersen Investigator award to Professor Roger Schibli and his team for the research proposal entitled, “Simultaneous Auger-Electron and β--Particle Therapy of Metastasized NET Using 161Tb-DOTATOC”. The proposal emphasizes the multidisciplinary talents of the Center of Radiopharmaceutical Sciences, from radionuclide development (Dr. Nick van der Meulen) via preclinical research (PD Dr. Cristina Müller) to Good Manufacturing Practice (Susanne Geistlich). The final goal of this research project is to make 161Tb-DOTATOC available for clinical application.
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The Doktorandentag gives second- or third-year PhD students of the Institute of Pharmaceutical Sciences or associated institutions the opportunity to present their research projects. Mr. Käppeli presented his work entitled "Targeting the GLP-1 receptor on pancreatic beta-cells: signaling and radiopharmaceutical application".
 




Forschung mit radioaktiv markierten Folsäure-Verbindungen
Täglich nehmen wir mit unserer Nahrung Folsäure auf. Dieses Vitamin ist wichtig für die Zellteilung und somit für das Wachstum. Doch in Zukunft könnte dem Vitamin noch eine weitere Rolle zukommen. Denn am PSI werden Therapien gegen Krebs entwickelt, die Folsäure nutzen.
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The Center Radiopharmaceuticals Sciences is a member of the FP7 consortium “BetaCure”, a collaboration between 17 research institutions and companies throughout whole Europe. The aim of the project “Personalized diagnosis and treatment of hyperinsulinemic hypoglycaemia caused by beta-cell pathology” is to develop new treatment modalities for rare beta-cell derived hyperinsulinemic diseases like Nesidioblastosis or Insulinoma. Nesidioblastosis is a hyperplasia of the beta-cells which lead to a hyperproduction of insulin in newborns. Insulinomas are tumors derived from beta-cells. These diseases are potential life threatening because of its hypoglycemic pattern and have only limited therapeutic modalities. The consortium is clinical oriented with a strong part of preclinical research and has a close collaboration with patient organizations related to these diseases. The project started on 1st of April 2014.
 


The Center for Radiopharmaceutical Sciences is a research partner in the project entitled “New Molecular-Functional Imaging Technologies and Therapeutic Strategies for Theranostic of Invasive Aspergillosis” (MATHIAS) funded by the European Union in the 7th Framework Programme. The main goal of this collaborative project is the development of radiolabeled antibodies for clinical diagnosis of invasive Aspergillosis by PET imaging. The preclinical evaluation of different antibody fragments for imaging and radioimmunotherapy are additional goals of MATHIAS. The project started on 1st October 2013 and the duration of the project is five years.
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Cancer Network Zurich-Cancer Biology Ph.D. Program Travel Grant:
The Cancer Biology Ph.D. Program awarded a travel grant to NASTASSJA TERRANEO to visit the 25th Annual Meeting of AGRR 2017 in Munich.

SIMON KÄPPELI also received a travel grant in 2017 to work with Professor Martin Gotthardt at the Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen, Netherlands on a BetaCure project