Research at the Institute of Radiopharmaceutical Cancer Research
Research field: Health
Within the research field Health of the Helmholtz association, scientists work towards elucidating the causes and pathogenesis of complex human diseases such as cancer. On this basis, strategies for early detection, prevention, diagnosis and therapy are developed. HZDR is participating with three institutes within the programme cancer research. Due to the importance of radioactive substances in life sciences – especially in medical diagnostics and therapy – our institute’s research is focussed on the development and application of radioactive drugs, particularly “Radiopharmaceutical Tumour Research”, under the mission statement “Molecular Imaging and Therapy of Tumours”.
Multimodal imaging and radionuclide-based therapeutics
Molecular imaging as based on the application of radiopharmaceuticals (radiotracers) represents an established method of routine diagnostics, which has been used in nuclear medicine for long time. However, development of positron emission tomography (PET) has enabled to visualise and quantify selected processes inside the body by means of in vivo biochemistry. In turn, this will allow individualised diagnostics of patients, provided that the methodology is consistently used. All that is critically dependent on the development of both highly specific radioactive molecular probes as well as computational methods of image reconstruction and data evaluation.
The institute collaborates with the Clinic and Policlinic for Nuclear Medicine and the Clinic and Policlinic for Radiation Therapy and Radiooncology within the shared PET centre Dresden-Rossendorf at the site of University Hospital Dresden. Interdisciplinary research that involves the application of the above-mentioned probes for medical research and to patients is followed in that centre.
Prerequisite for these translational research projects is the daily production of radiopharmaceutical according to the German Pharmaceutical Act and to the standards of GMP as well as the radiochemical, radiopharmaceutical and radiopharmacological development and evaluation of substances. Radiopharmaceutical production and preclinical radiochemical and radiopharmaceutical research is based on HZDR sites at Dresden-Rossendorf and Leipzig, respectively. The followed research projects include investigations towards the development, biological characterisation and production of substances labelled with short-lived radiotracers such as 18F and 11C based on a broad spectrum of compounds. Research interests with regards to tumour biochemistry are focussed towards the PET-supported elucidation of processes involving transport, metabolism and signal transduction in normal, injured and cancerous tissues. Searching for biological targets that are amenable to radiopharmaceutical development is an important task in that context. Closely connected to these projects is the development of radionuclide therapeuticals for endoradionuclide-based therapy. This includes basic research towards production and application of alternative radionuclides, radiolytically and metabolically stable chelators as well as investigations towards labelling of therapeutically relevant compound classes such as peptides, antibodies, building blocks for nucleic acids and nanoscaled compounds. A dedicated department is dealing with the development of suitable antibodies.
The above-mentioned investigations include the development of radioactive building blocks, methods for labelling, techniques for obtaining antibodies and their fragments as well as research into unravelling the relationships between the chemical properties of molecules and their behaviour in biological systems such as cells, laboratory animals and – consequently – humans. Furthermore, this includes the production of the positron emitters mentioned above and non-standard radionuclides at the cyclotron. Equally important, quantitative imaging with regards to PET and PET combined with MRI has to be ensured. Therefore, the quality of quantitative tomographic information needs to be improved, which is concerning both the time-dependent tracer concentration as primary parameter as well as parameters derived thereof. These parameters are of utmost importance for medical applications and drug research. Hence, investigations towards the development of computer-based methods are performed, which will account for an optimal evaluation of the calculated parameters and pave the way to new procedures for the pharmacokinetic characterisation of radiopharmaceuticals.
Consequently, the institute’s staff is performing research in the three following comprehensive fields:
- Radionuclide-based theragnostics
- Positron emission tomography / Multimodal Imaging
Translation of research findings into commercial institutions of industry and medicine inside and outside of HZDR are very important for the profile of the institute.
Active collaborations with numerous commercial partners exist, which range from medium-sized companies to large-scale industry. Shared interests overarch the entire portfolio of radiopharmaceutical techniques ranging from classical industrial mandates over collaborative research until product marketing, which includes radiopharmaceuticals and software.
High potential is attributed to collaborations within industrial drug research. Due to the capability of visualising and measuring interactions between drugs and biological systems rapidly and non-invasively, PET is considered as a seminal technique for pharmaceutical research and development. Therefore, important contributions to the cost-efficient development of safe and efficacious drugs can be expected. The development of specialised radiochemical and pharmacological methodology and data analysis can lead to mutual benefit, as cooperative research between the pharmaceutical industry and the PET centre has demonstrated.
A view into the human body
The following cartoon movie shows, how metabolic information on the human body can be obtained by using radioactively labelled compounds in combination with positron emission tomography.