CIBM PET HUG-UNIGE SECTION

Molecular Imaging

Section Head: Prof. Valentina Garibotto (HUG-UNIGE)

The advent of molecular imaging with Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) has enabled the in vivo visualization, characterization, and quantification of biological processes on cellular and even sub-cellular level. At the CIBM PET HUG UNIGE Section, we utilize these methods to develop new preclinical models and to make them available for a wide variety of research topics, namely the development of novel cancer theranostics, or neuroscience research. Our combined PET/SPECT/CT scanner is situated at the UNIGE PIPPA facility, which offers a wide range of cutting-edge technologies including high-resolution Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Optical imaging. Thanks to this synergy between CIBM and PIPPA, we are providing academic and non-academic collaborators with state-of-the-art multimodal preclinical imaging.

RESEARCH TOPICS

Focused ultrasound to improve therapeutic and radioligand entry into the brain in preclinical models

Description: The progress in immunotherapy marked by the approval for clinical use of two anti-amyloid antibodies changes the landscape of drug development for Alzheimer’s disease (AD). Yet, a pivotal challenge in treating AD, and neurological conditions overall, lies in ensuring drugs can effectively penetrate the blood-brain barrier (BBB). Balancing therapeutic effectiveness with minimal side effects requests for a combine strategy intertwining brain delivery technology and pharmacology. We are using non-invasive transcranial focused ultrasound, with a dedicated annular phased array applicator, in preclinical models of AD to safely and transiently open the BBB and efficiently improve the entry of therapeutic molecules and radioligands into the brain in preclinical models. In vivo molecular imaging allows to follow the biodistribution and to determine the pharmacokinetics of therapeutics agents in addition to evaluate their beneficial effects on disease outcomes.

Investigator: Kelly Ceyzériat (CIBM PET HUG-UNIGE)

Collaborators: Philippe Millet (HUG/UNIGE), Benjamin Tournier (HUG/UNIGE), Rareș Salomir (HUG/UNIGE)

Hormonal modulation in Alzheimer’s disease

Description: Sex is one of the main risk factors for Alzheimer’s disease, with a higher prevalence in women. Moreover, androgen deprivation therapy (ADT) stands as a standard treatment for intermediate- and high-risk localized or locally advanced prostate cancer. Recent studies indicate a potential correlation between ADT and an increased risk of cognitive disorders like Alzheimer’s disease. However, it’s crucial to note that the evidence supporting this connection is heavily influenced by the retrospective nature of the studies examined. These studies vary significantly in their designs and in the diverse ways ADT was utilized, contributing to potential biases in the findings. We are consequently interested in deciphering the role of sex hormones in the onset and the progression of Alzheimer’s disease and use PET/SPECT imaging as a reliable and translational tool to assess Alzheimer’s disease hallmarks in preclinical models.

Investigator: Kelly Ceyzériat (CIBM PET HUG-UNIGE)

Collaborator: Thomas Zilli (Oncology Institute of Southern Switzerland)

Theranostic developments for diagnostic and radioligand therapy

Description: The theranostic principle in nuclear medicine involves using the same target for both imaging and therapy, with a molecule which is radiolabelled differently or administered in different dosages. The diagnostic evaluation provides valuable insights into anticipating whether a tumour is likely to respond from a specific treatment, enabling a patient-tailored radioligand therapy based on the individual molecular characteristics of the tumour. Effective theranostic strategies, combining diagnostic through molecular imaging using positron or gamma-emitters and therapy using alpha or beta-emitters for precise radiation delivery are now established tools in clinic. Through a complete production and validation pipeline we aim to develop ⁶⁸Gallium and ¹⁷⁷Lutetium-based radioligands as theranostic pairs for novel cancer molecular targets.

Investigator: Olivia Bejuy (CIBM PET HUG-UNIGE)

Collaborators: Andrea Grotzky (Cyclotron Unit, HUG), Didier Colin (Preclinical Imaging Platform PIPPA, UNIGE), Oliver Hartley (UNIGE)

In ovo model for cancer theranostics

Description: The rapid development of new theranostic tools that use the same target for both imaging and therapy requires an efficient preclinical pipeline. We propose an alternative in ovo approach utilizing the chorioallantoic membrane (CAM) of chick embryos to bridge the gap between in vitro and in vivo experiments. Focusing on CAM models of prostate cancer, our objective is to demonstrate that this model serves as a robust platform for identifying efficient theragnostic strategies. Furthermore, we aim at validating the model’s imaging capabilities under longitudinal, multimodal, and non-invasive conditions by PET/SPECT/CT, MRI and optical imaging.

Investigators: Olivia Bejuy (CIBM PET HUG-UNIGE)

Collaborators: Didier Colin (Preclinical Imaging Platform PIPPA, UNIGE)