Opis projektu
Obrazowanie metodą PET na potrzeby diagnozowania schizofrenii
Diagnozowanie schizofrenii stanowi istotne wyzwanie medyczne ze względu na brak specyficznych biomarkerów. Chociaż dowody naukowe wskazują na zróżnicowaną ekspresję receptorów kwasu gamma-aminomasłowego (ang. gamma-aminobutyric acid, GABA) w mózgu pacjentów cierpiących na to zaburzenie psychiczne, to pochodzą one z badań pośmiertnych. Dlatego też naukowcy pracujący w ramach finansowanego ze środków UE projektu GABARPET proponują opracowanie sond do pozytonowej tomografii emisyjnej (ang. positron emission tomography, PET) mogących pozyskiwać ilościowe informacje na temat ekspresji poszczególnych podjednostek receptora GABAA u pacjentów. Aby zniwelować problem nieprzepuszczalności bariery krew-mózg, wspomniane sondy PET zostaną stworzone w formie przeciwciał bispecyficznych, które obierają za cel zarówno GABAA, jak i receptory transferyny. Wyniki doprowadzą do zrozumienia podstaw biologii schizofrenii i poprawy w zakresie diagnozowania choroby.
Cel
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.
Dziedzina nauki
Słowa kluczowe
Program(-y)
Temat(-y)
System finansowania
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordynator
20014 Turku
Finlandia