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Updated: Nov 24, 2025

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Targeted Radiotherapeutics from 'Bench-to-Bedside'
Cristina Müller1, Martin Béhé1, Susanne Geistlich1
1Center for Radiopharmaceutical Sciences, Forschungsstrasse 111, Paul Scherrer Institute, CH-5232 Villigen-PSI, Switzerland.
Abstract:
The concept of targeted radionuclide therapy (TRT) is the accurate and efficient delivery of radiation to disseminated cancer lesions while minimizing damage to healthy tissue and organs. Critical aspects for successful development of novel radiopharmaceuticals for TRT are: i) the identification and characterization of suitable targets expressed on cancer cells; ii) the selection of chemical or biological molecules which exhibit high affinity and selectivity for the cancer cell-associated target; iii) the selection of a radionuclide with decay properties that suit the properties of the targeting molecule and the clinical purpose. The Center for Radiopharmaceutical Sciences (CRS) at the Paul Scherrer Institute in Switzerland is privileged to be situated close to unique infrastructure for radionuclide production (high energy accelerators and a neutron source) and access to C/B-type laboratories including preclinical, nuclear imaging equipment and Swissmedic-certified laboratories for the preparation of drug samples for human use. These favorable circumstances allow production of non-standard radionuclides, exploring their biochemical and pharmacological features and effects for tumor therapy and diagnosis, while investigating and characterizing new targeting structures and optimizing these aspects for translational research on radiopharmaceuticals. In close collaboration with various clinical partners in Switzerland, the most promising candidates are translated to clinics for 'first-in-human' studies. This article gives an overview of the research activities at CRS in the field of TRT by the presentation of a few selected projects.
Insights
Targeted radionuclide therapy (TRT) precisely delivers radiation to cancer cells. Research focuses on identifying cancer targets, developing selective targeting molecules, and utilizing optimal radionuclides for effective tumor treatment.
Area of Science:
- Nuclear medicine
- Radiopharmaceutical sciences
- Oncology
Background:
- Targeted radionuclide therapy (TRT) aims to deliver radiation effectively to cancer lesions while sparing healthy tissues.
- Successful TRT relies on identifying cancer-specific targets, developing high-affinity targeting molecules, and selecting appropriate radionuclides.
- The Center for Radiopharmaceutical Sciences (CRS) possesses unique infrastructure for radionuclide production and certified laboratories for radiopharmaceutical development.
Purpose of the Study:
- To provide an overview of research activities at CRS in the field of TRT.
- To highlight the development of novel radiopharmaceuticals for cancer therapy and diagnosis.
- To showcase the translation of promising radiopharmaceutical candidates into clinical studies.
Main Methods:
- Identification and characterization of cancer cell-specific targets.
- Selection and optimization of targeting molecules (chemical or biological) with high affinity and selectivity.
- Selection of radionuclides with suitable decay properties for therapeutic and diagnostic applications.
- Preclinical evaluation using nuclear imaging equipment.
- Preparation of drug samples in Swissmedic-certified laboratories for human use.
Main Results:
- Exploration of non-standard radionuclides for tumor therapy and diagnosis.
- Investigation and characterization of novel targeting structures.
- Optimization of radiopharmaceutical properties for translational research.
- Successful translation of promising candidates to 'first-in-human' studies through clinical collaborations.
Conclusions:
- CRS is well-positioned to advance TRT due to its integrated infrastructure and expertise.
- The research encompasses the full spectrum from target identification to clinical translation.
- Collaborative efforts are crucial for bringing innovative radiopharmaceuticals to patients.
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