Project description
PET scan for schizophrenia diagnosis
Schizophrenia diagnosis presents a significant medical challenge due to the absence of specific biomarkers. Although evidence suggests differential expression of gamma-aminobutyric acid (GABA) receptors in the brain of patients with this mental disorder, this comes from post-mortem studies. Therefore, scientists of the EU-funded GABARPET project propose to develop positron emission tomography (PET) probes capable of unveiling quantitative information on specific GABAA receptor subunits expression in patients. To overcome the impermeability of the blood-brain barrier, these PET probes will be created as bi-specific antibodies that target both GABAA and the transferrin receptors. The results will provide fundamental insight into the biology of schizophrenia and improve disease diagnosis.
Objective
Changes in GABA receptors are known hallmarks for numerous neurological diseases including schizophrenia which is a severe psychiatric disorder that has a profound effect on both the individuals affected and society. The diagnosis of schizophrenia is complex because of the loss of high specific biomarkers. Research papers have suggested that the differential expression of GABAA receptors in the brain is associated with this mental disease. The current evidence on GABAergic abnormalities in schizophrenia is mostly based on postmortem studies and, in this sense, in vivo measurements of GABAA receptor subunits can reveal additional insights.
This project will develop Positron Emission Tomography (PET) probes which could unveil quantitative information about GABAA receptor expression in schizophrenia patients. However, the lack of imaging tracers with high affinity and specificity do not shed a clear light on the diagnosis in a traditional PET setting. In this sense, the immune-positron emission tomography (immunoPET) is a non-invasive technology based in antibody imaging which reveals a specific and sensitive molecular characterization of the cell surface phenotype in vivo. Nevertheless, its success in neuroimage is limited because of intact antibodies cannot penetrate the Brain Blood Barrier (BBB) in healthy conditions. However, GABARPET will tap into a small recombinant bispecific antibody construct targeting the GABAA receptors as well as the transferrin receptor because it is able to readily transmigrate across the BBB in vivo after peripheral injection.
This project wants to develop di-single-chain variable fragment (di-scFv) directed to α1 and α2 subunits of GABAA receptors. Then, they will be labeled with conventional radionuclides produced by cyclotron as 18F and 89Zr. ImmunoPET probes will be used in wild-type mice, GABAA receptor knockout mice and different kind of rodent models of schizophrenia.
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
20014 Turku
Finland