Cimbi

The Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) was founded on a collaboration between a number of research institutions in Copenhagen and was generously funded by 80 mio DKK from the Lundbeck Foundation between 2006-2015. Read more about the history of Cimbi here. And read more about the Cimbi Database, Cimbi Biobank and data requests here.
cimbi logo wide LF 634x150 Today, Cimbi acts as a figurehead for the collaboration between the Neurobiology Research Unit (NRU) at Rigshospitalet and the Department of Drug Design and Pharmacology, University of Copenhagen (KU). The primary investigators at the respective institutions are Professors Gitte Moos Knudsen and Matthias Herth.

Additional institutions involved in the collaboration:

PET and Cyclotron Unit – Jacob Madsen, Nic Gillings & Vladimir Shalgunov, Denmark. Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet.
University of Helsinki - Eero Castrén, Finland. Trophins Lab
Centre for Addiction and Mental Health – Neil Vasdev, Canada. Brain Health Imaging Centre
University of Copenhagen – Kristian Strømgaard, Denmark. Department of Drug Design and Pharmacology, University of Copenhagen, Strømgaard Lab
University of Copenhagen – Anders A. Jensen, Denmark. Department of Drug Design and Pharmacology, University of Copenhagen, Anders A. Jensen Group
Psychoactive Drug Screening Program – Bryan Roth, USA. National Institute of Mental Health, Roth Lab.

Research aims

After 2015, three main lines of research have carried on, namely 1) the nomenclature of radioligands developed within the framework, 2) the Cimbi database, and 3) the Cimbi biobank. In 2016 we published an inventory of the database in NeuroImage, which includes multimodality neuroimaging containing data from healthy volunteers and patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression.

Through joint funding between Professor Knudsen and Professor Herth, the Cimbi collaboration continues to expand on its’ historical aim of uncovering basic questions regarding interindividual differences in behavior and personality likely to be causally related to variations in the serotonergic transmitter system. The current focus remains on gaining a mechanistic understanding of the serotonergic system and expanding to include neuroplasticity, as well as investigating drug interactions with these systems. The applications of Cimbi projects are focused to neuropsychiatric disorders, including depression, anxiety and memory disorders.

Methods

All methods utilized throughout Cimbi projects are focused on the development, evaluation and translation of radiopharmaceuticals. We are currently focused on preclinical evaluation of novel radiopharmaceuticals through the following methods:

Preclinical neuroimaging studies, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT).
Drug occupancy measures – in vivo pharmacology.
Radiochemistry development for novel radiopharmaceutical production.
Pretargeting method development for in vivo click chemistry to utilize highly specific antibodies shuttled across the blood brain barrier (BBB) by carrier proteins and later administer the radiotracer to “click” onto the antibody bound to the specific target.
Focused ultrasound to improve the BBB penetration of low or non-brain penetrable radioligands.
Ex vivo or in vitro autoradiography to determine pharmacological parameters of novel and existing radiotracers, assess brain penetration, signal-noise ratio, selectivity, and other binding characteristics.
Biochemical and immunoassays to assess target expression before and after drug intervention, determine activation state of receptors and kinases, assess tissue distribution of the target of interest.

Expected Outcomes

Synthesize and radiolabel a range of pathway selective 5-HT2AR agonist PET tracers with subsequent neuroimaging validation in animals.
Establish relationships between dose of different 5-HT2AR agonists, behaviour/drug effects and cerebral 5-HT2AR occupancy in pigs and humans.
Investigate the neuroplastic effects of different 5-HT2AR agonists in pigs and humans.
Develop PET radiotracers to image targets associated with neuroplasticity, including the BDNF/TrkB signaling pathway.

Funding Sources

Nordisk Foundation – Neuroplastic effects of psychedelics – A NOVO Nordisk Foundation Tandem Project (Application Number: 0082288); Primary applicant: Gitte Moos Knudsen; Co-applicant: Matthias Herth.
Lundbeck Foundation – From psychedelics to novel therapeutics: Positive allosteric modulators of the BDNF receptor TrkB (Application Number: R383-2022-168);Primary applicant: Anders Asbjørn Jensen; Co-applicants: Gitte Moos Knudsen, Jesper L. Kristensen, Kasper Harpsjøe, Eero Castrén, Ilpo Vattulainen, Sari Lauri.
EU Marie Skłodowska-Curie Postdoctoral Fellowship – Nerve Growth Factor Delivery into the Brain – focus on therapeutic potential in Alzheimer's disease and In Vivo Evaluation via PET; Primary applicant: Tobias Gustavsson.
Lundbeck Foundation Postdoctoral Fellowship – PET Radiotracer Development for the BDNF Signaling Pathway (Application number: R449-2023-1465); Primary applicant: Cassis Varlow.
BRIDGE – Translational Excellence Programme – PET Imaging of PSD-95 – Unlocking the Quantification of Postsynaptic Density; Primary applicant: Sophie Stotz.
Neuroscience Academy of Denmark – Preclinical Pharmacological Characterization of Classical Psychedelics and their Behavioral and Persistent Molecular Effects; Primary applicant: Clara Madsen.

Ongoing Projects

Cerebral Serotonin 2A Receptor Occupancy of Psychedelic and Non-Psychedelic Compounds as Measured In Vivo in Pigs (Clara Madsen, PhD Student, NRU)
Synthesis and evaluation of ¹¹C-phenethylamine analogues as PET tracers for the imaging of 5-HT_2A receptors (Merlin Zabrocki, PhD Student, KU)
Design and Evaluation of Immuno-PET Imaging Ligands for BDNF and TrkB, and a Novel Tetrazine in Brain Pre-targeting (Tobias Gustavsson, Postdoc, KU)
Preclinical neuroimagaing of TrkB in the pig brain and radiotracer development for the BDNF signaling pathway (Cassis Varlow, Postdoc, NRU)
[¹⁸F]Fluorotryptophan to visualize serotonin synthesis in the brain (Sophie Stotz, Postdoc, KU)
Preclinical validation of novel TrkB agonists and their persistent molecular effects compared to 5-HT2A receptor activation (Elisabeth Frandsen, PhD Student, NRU)

Annual Meeting

After reflecting on the growing list of projects between Professors Knudsen and Herth, we brought together the team members working on these joint projects at the 1^st annual CIMBI Symposium which was hosted on September 4, 2024.

The overall theme of this meeting is the development and evaluation of radiopharmaceuticals across the different projects. We also welcomed two invited speakers from the Center for Antibody Technology at the Technical University of Denmark (DTU), Dr. Andreas Hougaard Laustsen and Dr. Christoffer Vinther Sørensen. Dr. Andreas Hougaard Laustsen spoke about his work on how to discover and engineer antibodies with special binding properties. Dr. Christoffer Vinther Sørensen discussed applications for antibodies with pH-dependent antigen binding properties. It was a pleasure to see familiar faces, meet new colleagues, and dive into discussions on our current cutting-edge brain research. We had extensive discussions on our ongoing projects and made significant progress in deciding the next steps for our future endeavors. Looking forward to the 2025 annual Cimbi meeting (date TBA) and continued advancements in the field of molecular brain imaging.

Standing from the left: Vasiliki Andrianopoulou, Andreas Laustsen-Kiel, Nic Gillings, Vladimir Shalgunov, Tobias Gustavsson, Jacob Madsen, Gitte Moos Knudsen, Chris Poulie, Matthias Herth, Icaro Simon, Christian O Bech-Bartling, Christoffer Vinther Sørensen. Sitting from the left: Sophie Stotz, Merlin Zabrocki, Cassis Varlow, Clara Madsen, Elisabeth Kolesnik, Frederikke Hassing.