Peter Bernhardt

Individualized radiopharmaceutical cancer therapy through advanced imaging, dosimetry, and response modelling

Radioligand therapy has emerged as an important treatment option for patients with metastatic cancer, enabling targeted delivery of ionizing radiation to tumour cells while largely sparing surrounding healthy tissues. This therapeutic strategy has demonstrated substantial clinical benefits in diseases such as somatostatin receptor-positive neuroendocrine tumours and metastatic castration-resistant prostate cancer. Despite these advances, treatment response and toxicity vary markedly between patients, underscoring the need for improved methods to individualize therapy. A major challenge lies in accurately characterizing tumour burden, radiation dose distribution, and the response of radiosensitive normal tissues, particularly the bone marrow.

The overarching aim of this project is to advance precision radioligand therapy by developing and integrating novel methods for imaging, dosimetry, and biological response modelling. Advanced Monte Carlo-based simulations and artificial intelligence techniques will be employed to improve the quality and quantitative accuracy of SPECT imaging. These developments will enable more reliable measurements of radiopharmaceutical uptake in tumours and normal tissues, forming a robust basis for patient-specific absorbed dose calculations. Reduced image noise and improved spatial resolution are particularly important for assessing activity in the bone marrow, where current imaging approaches are limited.

In parallel, the project will develop mathematical models describing metastatic dissemination and treatment response. By linking longitudinal imaging data with tumour growth and response dynamics, these models aim to predict individual relapse risk and to optimize radiation dose levels and treatment intervals. Such modelling approaches have the potential to support clinical decision-making by identifying treatment strategies that maximize tumour control while minimizing toxicity.

A central component of the project is the refinement of bone marrow dosimetry and haematological response modelling. By incorporating patient-specific anatomical and biological information, including variations in bone marrow composition and the presence of infiltrative metastases, the project seeks to improve the prediction of radiation-induced haematological toxicity. This is essential for increasing treatment safety and for enabling more personalized patient selection and treatment planning.

The project integrates clinical data from ongoing radioligand therapy studies with preclinical investigations and is conducted in close collaboration with national and international partners. Particular emphasis is placed on evaluating the therapeutic potential of the novel radionuclide terbium-161, which emits short-range electrons that may be especially effective against small or diffuse metastatic lesions. Overall, the project aims to generate new knowledge and tools that support safer, more effective, and more individualized radioligand therapies, with the long-term goal of improving outcomes and quality of life for patients with advanced metastatic cancer.