Research Program E Radiological Diagnostics and Introduction

Research Program Radiological Diagnostics and Therapy Coordinator: Prof. Dr. med. Dr. rer. nat. Wolfhard Semmler

Oncological Diagnostics and Therapy (E0100 / E010) The primary goal pursued by the Research Program ‘Ra- Prof. Dr. med. Gerhard van Kaick (until 10/02) diological Diagnostics and Therapy’ is the introduction of  06221 42-2600, FAX 06221 42-2595 new results, procedures and techniques into cancer diag- e-mail: [email protected] nostics and therapy, and to individualize the handling and treatment of each patient. Achieving these goals will lead Prof. Dr. med. Hans-Ulrich Kauczor (since 01/03) to a significant increase in local tumor control and in turn  06221 42-2563, FAX 06221 42-2567 the cure rate. The multidisciplinary research program is e-mail: [email protected] supported by four divisions and two clinical research Biophysics and Medical Physics (E0200 / groups affiliated with the Department of , E020) and the Department of Nuclear of the University Prof. Dr. med. Dr. rer. nat. Wolfhard Semmler Clinic Heidelberg. The complexity of the problem demands  06221 42-2550, FAX 06221 42-2613 the close cooperation between physicians, physicists, e-mail: wolfhard.semmler@ dkfz.de mathematicians, information scientists, engineers, radio- and Radiopharmacology (E0300 / chemists, and biologists. Radiodiagnostic procedures will E030) continue to be of great importance for early tumor detec- Prof. Dr. rer. nat. Michael Eisenhut tion , the evaluation of the stage of the , treatment planning, monitoring, and follow-up. Increasing impact can  06221 42-2443, FAX 06221 42-2572 e-mail: m.eisenhut@ dkfz.de be expected from procedures which allow us to investigate organ function and physiological pathways. With respect Medical Physics (E0400 / E040) to certain cancer , the five year survival rate de- Prof. Dr. rer. nat. Wolfgang Schlegel fined as a cure has increased only gradually during the  06221 42-2551, FAX 06221 42-2561 last decades. e-mail: w.schlegel@ dkfz.de The objectives of the Division of Oncological Clinical Cooperation Unit Radiation Oncology (E0500 / Diagnostics and Therapy (E0100 / E010) are: E050) • Early Tumor Detection • PD Dr. med. Dr. rer. nat. Jürgen Debus Tumor Staging • Prognostic Assessment  06221 42-2515, FAX 06221 42-2514 219 • Support of Therapy Planning e-mail: j.debus@ dkfz.de • Therapy Monitoring and Assessment of Clinical Cooperation Unit (E0600 / Therapy Response E060) • Follow – Up • Prof. Dr. med. Uwe Haberkorn Screening of high risk populations  06221 56-7732, FAX 06221 56-5473 As well as the improved visualization of tumors, the inves-  06221 42-2477 tigation of functional parameters of the tumor tissue (e.g. e-mail: u.haberkorn@ dkfz.de related to microcirculation or metabolism) is gaining impor- tance for the assessment of the individual disease. These parameters are also increasingly taken into account during radiation therapy and therapy monitoring. Together with related clinical / scientific projects, we are also conducting fundamental experimental studies. For these tasks, we use and devise contemporary imaging techniques such as multi-slice spiral computed tomogra- phy (CT), magnetic resonance imaging (MRI) as well as sonography and color Doppler ultrasound. Technical im- provements and innovations are achieved in close coop- eration with the Division of Biophysics and Medical Radia- tion Physics of the Research Program E (Radiological Di- agnostics and Therapy). Our methods are clinically ap- plied and critically evaluated together with our neighboring clinical cooperation units Radiooncology and Nuclear Medicine, as well as the hospitals of the Tumor Center Heidelberg / Mannheim. The research and development program of the Division of Biophysics and Medical Radiation Physics (E0200 / E020) is multidisciplinary and focuses on basic and ap- plied physical and biological research in the radiological diagnostics of cancer as well as related technical develop-

DKFZ 2003: Research Report 2001/2002 Research Program E Radiological Diagnostics and Therapy Introduction

ments and , in particular . The ultimate goals of the divis- are going to develop is called Adaptive Cone Beam ion‘s program are to assess the baseline data for individu- Therapy. It will combine conformal dose delivery with on- alized tumor therapy and improved local tumor control. line imaging of 3D anatomy and on-line monitoring of 3D This means a complete qualitative and quantitative deter- dose distributions. mination of the individual patient‘s disease with respect to Based on the experience and technology from radio- morphological, functional and biochemical characteristics therapy developments, we are also going to develop and as far as can be evaluated using biomedical imaging tech- investigate new methods in Neurosurgery, especially using niques such as emission tomography (PET), short pulsed lasers. The skills of the Division cover Com- magnetic resonance imaging (MRI), magnetic resonance puter science, Medical Radiation Physics, Mathematics, spectroscopy (MRS), ultrasound diagnostics, and X-ray- as well as Mechanical and Electronic Engineering. It is computed tomography (CT). These baseline data may one of the major advantage of our division that prototypes then be used for individualized treatment planning (e.g., of software and hardware developments can directly be with radiation, hyperthermia, , or combinations transferred within the same building into clinical applica- thereof), serving as a basis with which to assess the thera- tion in close connection and cooperation with the Clinical peutic effects during and after treatment, and if necessary, Cooperation Unit Oncological Radiotherapy (J.Debus). modify the treatment. Thus the Divison is also active in testing and evaluating The scientific program currently performed at the Division the new techniques as well as in establishing adequate of Radiochemistry and Radiopharmacology (E0300 / QA programs. E030) is summarized by the following topics: 1. Develop- The Clinical Cooperation Unit Radiation Oncology“ is act- ment and preclinical evaluation of new low molecular ing in close cooperation with the Radiological University weight imaging agents, which are applicable for positron Hospital Heidelberg and other Divisions of the Research emission tomography, PET and single emission Program. The new Heavy Ion Therapy Project at the Labo- computerized tomography, SPECT. 2. Production of radio- ratory for Heavy Ion Research (GSI) in Darmstadt is devel- pharmaceuticals in compliance with GMP standards. Be- oped together with the department of Radiation Therapy sides production this includes quality control and exten- University Clinics Heidelberg. sive amount of documentation. 3. Development of pretar- The Clinical Cooperation Unit Nuclear Medicine com- geting systems for immunoscintigraphy (IS) and radio- bines activities in the University Hospital and the DKFZ to immunotherapy (RIT) using bispecific antibodies and ra- use nuclear medical methods as Positron-Emission-Tomo- diolabeled metal complexes. 3. Development of carrier graphy (PET) and Single Emission Tomography molecules for the targeted transport of drugs into tumor 220 (SPECT), to monitor biochemical and physiological pro- cells. This includes radioisotopes, cytostatics, antisense cesses in tumors in the framework of clinical, experimental oligonucleotides and other cytotoxic agents. animal and cell biological studies. The Division operates a 32 MeV for pro- A focus of the division is the gene therapy of malignant tu- duction and laboratories suitable for the processing of ra- mors: construction of tissue specific viral vectors, transfer dioactive substances required for the diagnosis and of suicide genes in malignant tumors, anti-angiogenesis therapy of tumors. Related to this area of research, the di- and the planning and monitoring of these gene- vision offers an extensive service program for internal and therapeutical attempts. external partners. In order to fulfill increasing demands Further projects are the distribution of radioactive labelled and eventually obtain a licence for the production and antisense oligonucleotides, radioactive labelled chemo- large-scale distribution of , refurbish- therapeutica, the monitoring of apoptosis as well as the ing and improvement of the laboratories is in progress. development of new nuclear medical therapies. Failure of local tumor control is still a problem in about 20% of all cancer patients. Due to this fact, there is an ur- gent need for the optimization of existing and development of new and more effective treatment techniques for local- ized tumors. Research at the Division of Medical Physics is focused on new conformal radiotherapy techniques with photons, and . Major achievements of the last two decades were the introduction of 3D treatment planning, Stereotactic , 3D Conformal Preci- sion Radiotherapy, inverse treatment planning, Intensity Modulated Radiotherapy and Radiotherapy with Carbon- 12 Ions. Besides the ongoing projects in -therapy, our future work will be concentrated on establishing mathematical and biological models of tumor and normal tissue re- sponse and on the consideration of dynamic changes of target volumes (PTVs) and organs at risk (OARs) under therapy, either caused by therapeutic response, by organ movements or by patient repositioning. The approach we

DKFZ 2003: Research Report 2001/2002