68Ga-DFO based PET-Imaging of Infections

Despite the success of antibiotics, bacterial infections are still a serious global healthcare problem. Molecular imaging has the potential for specific and sensitive detection of infections, replacing current methods based on biopsy or anatomical imaging. One of few microbe specific targets is the Siderophore system, which does not exist in human cells. Siderophores are small iron binding molecules specifically recognized by bacteria. Iron can be replaced by the radioactive isotope Gallium-68 without loss of bioactivity. Administration of these labelled siderophores allows molecular imaging by positron emission tomography (PET). In recent studies, we could show that the siderophore deferoxamine, an already clinically established drug used to treat iron overload disease (Desferal), can be radiolabelled with Gallium-68 and used for imaging of bacterial infections. In preclinical studies, excellent imaging of various clinically relevant bacterial infections from Pseudomonas, Staphylococcus and Strepotococcus was achieved. In this project a clinical study is performed using Gallium-68-deferoxamine for imaging bacterial infections by PET. The aim is to establish the safety, distribution and preliminary diagnostic performance of this new radiopharmaceutical to prove that this imaging approach is safe, provides acceptable radiation dose and allows direct targeting of invading bacteria. In total 15 patients with proven bacterial infections will undergo PET imaging, a variety of clinically relevant infections will be included to assess initial diagnostic sensitivity. For the first time this clinical study will provide data of a novel diagnostic PET radiopharmaceutical for direct imaging of infection with the potential to replace current imaging techniques delivering a more sensitive and specific detection and confirmation of infections. Several researchers experienced with clinical trials at the Medical University of Innsbruck are involved: Clemens Decristoforo will coordinate the project and is responsible for study drug preparation. Irene Virgolini, as Nuclear Medicine physician, will act as principle investigator supported by Bernhard Nilica, and Günther Weiss, infectiologist will provide expertise in clinical infections. A cooperation with the Palacky University in Olomouc, Czech Republic (Marian Hajduch, Milos Petrik) will complement the project.

Infections represent one of the major global challenges in healthcare, particularly due to the increasing occurrence of resistant bacterial hospital pathogens. One of the key challenges is timely, specific, and accurate diagnosis in order to quickly initiate the appropriate therapy-especially when tissue samples are not accessible. Imaging diagnostic methods such as ultrasound, X-ray, CT, or MRI are based on anatomical-structural changes and are usually non-specific and insensitive. This project aimed to evaluate a new method based on molecular imaging using positron emission tomography (PET) in an initial clinical study involving patients with bacterial infections, focusing on its safety and initial diagnostic potential. Currently, PET imaging for infections relies on the use of 18F-FDG, a radioactively labeled sugar that accumulates non-specifically in inflammatory processes. The new method is based on gallium-68 labeled deferoxamine, a so-called siderophore that is specifically taken up by infectious bacteria to acquire iron, but is not recognized by human cells. Detection via PET enables specific visualization of bacterial infections, which had already been demonstrated in preclinical studies. The PET imaging study using 68Ga-deferoxamine for bacterial infections was approved by the ethics committee and the drug regulatory authority and commenced in early 2021. Initially, an automated process for the clinical production of the radiopharmaceutical 68Ga-deferoxamine was established. In a first phase, four patients with bacterial infections were examined at the Medical University of Innsbruck. The administration of 68Ga-deferoxamine showed no side effects and demonstrated a very low radiation exposure of 0.01 mSv/MBq. These examinations also allowed for visualization of the distribution of the new substance in the human body. By the end of 2024, ten additional patients had been included, bringing the number of enrolled patients close to the planned maximum. In particular, among patients with joint infections, accumulation of 68Ga-deferoxamine in the infectious focus could be demonstrated in the majority of cases. The findings were confirmed by routine diagnostics in most of the cases. With these data, the first clinical trial was successfully completed. The study, which marks the first application of a radioactive siderophore for imaging diagnosis of infections using PET, confirmed the safety of the method at low radiation exposure to the patient and demonstrated initial clinically diagnostic results. This forms the basis for establishing clinical use in further studies.