TY - JOUR
T1 - Radiosynthesis and Preliminary Biological Evaluation of [18F]VC701, a Radioligand for Translocator Protein
AU - Di Grigoli, Giuseppe
AU - Monterisi, Cristina
AU - Belloli, Sara
AU - Masiello, Valeria
AU - Politi, Letterio S alvatore
AU - Valenti, Salvatore
AU - Paolino, Marco
AU - Anzini, Maurizio
AU - Matarrese, Mario
AU - Cappelli, Andrea
AU - Moresco, Rosa M aria
PY - 2015
Y1 - 2015
N2 - Positron emission tomography (PET) can be used to monitor in vivo translocator protein (TSPO) expression by using specific radioligands. Recently, several [11C]PK11195 analogues have been synthesized to improve binding stability and brain availability. [18F]VC701 was synthesized and validated in CD healthy rats by biodistribution and inhibition analysis. Imaging studies were also conducted on animals injected unilaterally in the striatum with quinolinic acid (QA) to evaluate the TSPO ligand uptake in a neuroinflammation/neurodegenerative model. [18F]VC701 was synthesized with a good chemical and radiochemical purity and specific activity higher than 37 GBq/μmol. Kinetic studies performed on healthy animals showed the highest tracer biodistribution in TSPO-rich organs, and preadministration of cold PK11195 caused an overall radioactivity reduction. Metabolism studies showed the absence of radiometabolites in the rat brain of QA lesioned rats, and biodistribution analysis revealed a progressive increase in radioactivity ratios (lesioned to nonlesioned striatum) during time, reaching an approximate value of 5 4 hours after tracer injection. These results encourage further evaluation of this TSPO radioligand in other models of central and peripheral diseases.
AB - Positron emission tomography (PET) can be used to monitor in vivo translocator protein (TSPO) expression by using specific radioligands. Recently, several [11C]PK11195 analogues have been synthesized to improve binding stability and brain availability. [18F]VC701 was synthesized and validated in CD healthy rats by biodistribution and inhibition analysis. Imaging studies were also conducted on animals injected unilaterally in the striatum with quinolinic acid (QA) to evaluate the TSPO ligand uptake in a neuroinflammation/neurodegenerative model. [18F]VC701 was synthesized with a good chemical and radiochemical purity and specific activity higher than 37 GBq/μmol. Kinetic studies performed on healthy animals showed the highest tracer biodistribution in TSPO-rich organs, and preadministration of cold PK11195 caused an overall radioactivity reduction. Metabolism studies showed the absence of radiometabolites in the rat brain of QA lesioned rats, and biodistribution analysis revealed a progressive increase in radioactivity ratios (lesioned to nonlesioned striatum) during time, reaching an approximate value of 5 4 hours after tracer injection. These results encourage further evaluation of this TSPO radioligand in other models of central and peripheral diseases.
UR - http://www.scopus.com/inward/record.url?scp=84991273440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991273440&partnerID=8YFLogxK
U2 - 10.2310/7290.2015.00007
DO - 10.2310/7290.2015.00007
M3 - Article
C2 - 26044669
AN - SCOPUS:84930369581
SN - 1535-3508
VL - 14
JO - Molecular Imaging
JF - Molecular Imaging
ER -