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Development of Novel Exotic Radionuclides Towards Preclinical and Clinical Medical Applications

Applicant van der Meulen Nicholas
Number 188495
Funding scheme Project funding
Research institution Laboratorium für Radiochemie Paul Scherrer Institut
Institution of higher education Paul Scherrer Institute - PSI
Main discipline Inorganic Chemistry
Start/End 01.02.2020 - 31.01.2024
Approved amount 543'764.00
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All Disciplines (5)

Discipline
Inorganic Chemistry
Other disciplines of Engineering Sciences
Nuclear Physics
Chemical Engineering
Material Sciences

Keywords (3)

radionuclide development; cyclotron; exotic radionuclides

Lay Summary (German)

Lead
Produktion von therapeutischen und diagnostischen Radionukliden
Lay summary

In der Klinik gehört die nicht-invasive Bildgebung mit Radiopharmaka, die sogenannte Positronen Emissionstomographie (PET) respektive Einzelphotonen Emissionscomputertomographie (SPECT), heutzutage zu den Standarduntersuchungen bei Krebspatienten. In den letzten Jahren wurde auch die Radionuklidtherapie vermehrt eingesetzt, da diese für die Behandlung von metastasiertem Krebs besonders vielversprechend ist.

Ein theragnostisches Konzept, bei welchem dasselbe Zielmittel für die Bildgebung und die Behandlung verwendet wird, jedoch das Radionuklid entsprechend der Strahlungseigenschaften ausgetauscht wird, findet mehr und mehr Anklang. Die Idee, 44Sc als diagnostisches Gegenstück für PET zum therapeutischen Goldstandard 177Lu einzusetzen, ist wünschenswert, da beide Radionuklide ähnliche chemische Eigenschaften aufweisen. Die resultierenden Radiopharmaka sind sich deshalb sehr ähnlich.

Das Ziel des vorliegenden Projektes ist es, verlässliche Verfahren für die Produktion von therapeutischen und diagnostischen Radionukliden wie z.B. 165Er und 155Tb in grösseren Mengen und bester Qualität zu entwickeln. Die Eigenschaften der Zielscheiben für die Bestrahlung sowie die Bestrahlungsparameter müssen für alle Produktionsrouten bestimmt werden. Geeignete Trennungsverfahren sollen im Rahmen unserer Forschungstätigkeit entwickelt werden. Bei dieser technologischen Entwicklung, soll die IP2 Bestrahlungslinie am PSI eine Schlüsselrolle einnehmen, da sie Europaweit einzigartige Möglichkeiten bietet, solche Radionuklide herzustellen. Die neuen Radionuklide sollen dann in erster Linie für präklinische Versuche zur Verfügung gestellt werden, so dass ihre Eigenschaften untersucht werden können.

Es wird erwartet, dass die Ergebnisse unserer Forschung für die medizinische Anwendung relevant und potentiell für kommerzielle Zwecke interessant sind. Es ist wichtig, dass die Schweiz ihre Eigenständigkeit gegenüber anderen Forschungsanlagen weltweit mit ihrer bahnbrechenden Forschung beweisen kann.

Direct link to Lay Summary Last update: 06.12.2019

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Abstract

Radionuclides represent a powerful tool for cancer diagnostics and treatment. Depending on the purpose of the intended application, radionuclides that decay by means of a-, ß--, ?-emission are used for therapy, while radionuclides that decay by ß+- and ?-emission are used for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) diagnosis, respectively. The most popular radionuclides currently used for radionuclide therapy include 177Lu, 131I and 90Y. More recently, our laboratory has provided evidence that a combination of ß--emission and low energy <100 keV Auger electron emission (as e.g. found for 161Tb) show superior therapeutic efficacy. Actinides such as 223Ra (223RaCl3 - also known as Zofigo®) and 225Ac are gaining in popularity in nuclear medicine due to the fact that they are a-emitters, which can cause devastating damage to tumours or tissue over a short range. A concept that is gaining in popularity is that of “theragnostics”, where the same targeting agent is used for the imaging and treating of the tumour in question. Currently, the concept of theragnostics is applied using radiometals which are not identical. The idea of using 44Sc as a diagnostic counterpart to the therapeutic “gold standard” 177Lu is desirable due to the fact that both elements exhibit lanthanide-like properties, thereby, allowing both to be similarly labelled to a specific target (such as PSMA-617). Ideally, the concept should be applied using the same chemical element, as part of the so-called “matched pair” principle, to ensure identical target labelling and to ensure accurate imaging of the radionuclide therapy being conducted.Working Hypothesis and Goals: The current rate of change in the world of radiotherapy and diagnosis emphasizes the need of increasing the number of radionuclides to be made available to the clinicians, to assist them in the quest of finding the perfect target for therapy. While 161Tb is currently being prepared for the clinic, another radiolanthanide with Auger therapy potential is that of 165Er. While the radionuclide can be produced with a cyclotron via two separate nuclear reactions, no production of this radionuclide in high activities has been performed to date.Another radionuclide that can be introduced as part of the theragnostic concept is that of 155Tb. 155Tb (T1/2 = 5.3 d) is a radionuclide which can be used for tumour diagnosis via Single Photon Emission Computed Tomography (SPECT). The longer half-life of this nuclide can assist with the determination of the tumour dose when applied with its therapeutic counterpart, 161Tb. While this radionuclide has been produced using the ISOL facility at CERN, Switzerland, there is the possibility of using a cyclotron to produce it in high quantity using enriched Gd target material.The goal of the present project is, therefore, to establish and develop reproducible irradiation and separation methods to produce 165Er and 155Tb in high quantity and quality and prepare these products for preclinical study and, later, into a Good Manufacturing Practice (GMP) environment. It is envisaged to apply for a single PhD student towards this application. Targetry and irradiation parameters need to be determined for all production route possibilities, along with the development of chemical separation methods. The IP2 beam line at PSI will play an integral role towards the technology development of these radionuclides.Expected value of the proposal: the result ought to have a future medical impact on the community, along with a potential commercial impact. It is important that Switzerland can demonstrate independence from other facilities around the world with its groundbreaking research.
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