TY - JOUR
T1 - Monitoring disease evolution and treatment response in lysosomal disorders by the peripheral benzodiazepine receptor ligand PK11195
AU - Visigalli, Ilaria
AU - Moresco, Rosa Maria
AU - Belloli, Sara
AU - Politi, Letterio S.
AU - Gritti, Angela
AU - Ungaro, Daniela
AU - Matarrese, Mario
AU - Turolla, Elia
AU - Falini, Andrea
AU - Scotti, Giuseppe
AU - Naldini, Luigi
AU - Fazio, Ferruccio
AU - Biffi, Alessandra
PY - 2009/4
Y1 - 2009/4
N2 - Microglia activation and neuroinflammation play a pivotal role in the pathogenesis of lysosomal storage disorders (LSD) affecting the central nervous system (CNS), which are amenable to treatment by hematopoietic stem cell transplantation (HSCT). HSCT efficacy relies on replacing the intra- and extra-vascular hematopoietic cell compartments, including CNS microglia, with a cell population expressing the functional enzyme. Non-invasive and quantitative assessment of microglia activation and of its reduction upon HSCT might allow for evaluation of disease evolution and response to treatment in LSD. We here demonstrate that microglia activation can be quantified ex vivo and in vivo by PET using the peripheral benzodiazepine receptor ligand PK11195 in two models of LSD. Furthermore, we show a differential PBR binding following microglia replacement by donor cells in mice undergoing HSCT. Our data indicates that PBR ligands constitute valuable tools for monitoring the evolution and the response to treatment of LSD with CNS involvement, and enable us to evaluate whether the turnover between endogenous and donor microglia following HSCT could be adequate enough to delay disease progression.
AB - Microglia activation and neuroinflammation play a pivotal role in the pathogenesis of lysosomal storage disorders (LSD) affecting the central nervous system (CNS), which are amenable to treatment by hematopoietic stem cell transplantation (HSCT). HSCT efficacy relies on replacing the intra- and extra-vascular hematopoietic cell compartments, including CNS microglia, with a cell population expressing the functional enzyme. Non-invasive and quantitative assessment of microglia activation and of its reduction upon HSCT might allow for evaluation of disease evolution and response to treatment in LSD. We here demonstrate that microglia activation can be quantified ex vivo and in vivo by PET using the peripheral benzodiazepine receptor ligand PK11195 in two models of LSD. Furthermore, we show a differential PBR binding following microglia replacement by donor cells in mice undergoing HSCT. Our data indicates that PBR ligands constitute valuable tools for monitoring the evolution and the response to treatment of LSD with CNS involvement, and enable us to evaluate whether the turnover between endogenous and donor microglia following HSCT could be adequate enough to delay disease progression.
KW - Hematopoietic stem cell transplantation
KW - Lysosomal storage disorders
KW - Microglia
KW - Neuroinflammation
KW - Peripheral benzodiazepine receptor ligands
KW - Positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=62149152389&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62149152389&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2008.12.019
DO - 10.1016/j.nbd.2008.12.019
M3 - Article
C2 - 19320046
AN - SCOPUS:62149152389
VL - 34
SP - 51
EP - 62
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 1
ER -