Research
Quantitative molecular imaging via SPECT (Single-Photon-Emission-Computed-Tomography) or PET (Positron-Emission-Tomography) allows for a direct measure of the radionuclide distribution within the patient. Quantitative imaging is still a research field of interest, as it requires specific effort during the patient examination itself (e. g. patient positioning) and with regard to image reconstruction to correct for physical image degradation (e. g. detector response modeling). The accuracy of image reconstruction can be validated against Monte Carlo simulations of the desired imaging system. In addition to PET or SPECT, the patient anatomy can be imaged via accompanying Computed Tomography (CT) (hybrid SPECT/CT (see figure) or PET/CT). Automatic or semi-automatic image segmentation methods (e. g. kmeans clustering) are required to provide a fast, robust and user-independent detection of both, risk organs and tumorous tissue in those acquired images.
Dosimetry ideally requires the complete knowledge of the time course of radionuclide accumulation within all relevant tissues from radiopharmaceutical injection until the last radioactive decay. However, for a clinical surrounding, measuring the radionuclide distribution within the patient is only possible for a few selected time points (usually 3-4). Thus, appropriate mathematical curve models have to be fitted to these few data points to estimate the complete time course (time-activity-curve (TAC)). In doing so, time points of patient examination, mathematical fit model, and the pharmaceutical-specific accumulation have to be carefully synchronized (pharmacokinetic description).
Using the determined time-activity-curves, the physically absorbed dose of risk organs and lesions can be derived, as the physical properties of the employed radionuclides are known. More advanced 3D dosimetry techniques (Monte Carlo simulations) can model all relevant physical interactions underlying the radiation exposure within the patient after radionuclide administration for each single image sub-unit. However, Monte Carlo simulations are time-consuming and their routine clinical application is limited, compared to, e. g., less computationally demanding but also potentially less accurate absorbed dose conversion factors (S-values). Thus, appropriate dosimetry methods have to be selected according to the required accuracy and clinical feasibility.
To summarize, dosimetry for radionuclide therapy is a demanding multi-step process and its integration into clinical routine is strongly limited by clinical capabilities. Thus, we work in close connection with physicians, technicians, and chemists to develop standards as accurate as possible in agreement with clinical feasibility and patient comfort. To provide dosimetry solutions with a high degree of automation (e.g. automatic image segmentation) is mandatory to allow for an application in daily clinical routine.
The goal of radionuclide therapy is to achieve a highly selective irradiation of tumor cells via short-range radioactive decay products (electrons or alpha particles). The selective accumulation of the radioactive substance within the tumor tissue can be achieved, Theranostic_principlee.g., by metabolic trapping mechanisms or by localized administration (e.g. Iodine-131 for malignant or benign thyroid disease or Selective Internal Radiotherapy (SIRT) using Yttrium-90 for treatment of liver metastases). Many available radiopharmaceuticals employ so-called carrier molecules, which have the ability to target binding sites that are over- or specifically expressed by cancer cells. The design of such carrier-based pharmaceuticals is guided by the Theranostic concept. The Theranostic concept refers to the aim to label a specific carrier molecule either with therapeutic beta-minus-emitting or alpha-emitting radionuclides (e.g. Lutetium-177, Actinium-225), or diagnostic radionuclides applicable for PET or SPECT (e. g. Gallium-68, Fluorine-18,Technetium-99m).
Diagnostic molecular imaging allows for the identification of patients suitable to undergo radionuclide therapy, and further enables to measure the patient response after therapy. Many therapeutic radionuclides also emit decay products suitable for PET or SPECT imaging. This allows for a quantitative measure of the 3D radionuclide accumulation within the patient after radiopharmaceutical administration, which can be employed to estimate the patient-specific 3D absorbed dose distribution in a next step.
Starting from the administration of radioactive Iodine-131 for the treatment of benign or malignant thyroid disease in the 1930s, intensive ongoing work on radiopharmaceutical production rapidly increased the availability of therapy options for various types of cancer disease. Somatostatine analogues labelled with radioactive Lutetium-177 (peptide-receptor-radionuclide-therapy (PRRT)) became an established treatment option for inoperable, respectively metastasized neuroendocrine tumors. Via targeting of the prostate-specific membrane antigen (PSMA) overexpressed on prostate cancer cells, Lutetium-177-PSMA radioligand therapy (RLT) therapy has evolved as an attractive treatment option for metastasized castration-resistant prostate cancer, being top ranked for the cause of worldwide deaths of men. Since recently, Theranostics also offers alternatives to Lutetium-177-based compounds for PRRT or PSMA-RLT by usage of the alpha emitter Actinium-225.
