RT Journal Article
SR Electronic
T1 Radiolabeling and comparative studies of [18F]DPA-714, [18F]PBR111 AND [18F]FEDAA1106, potent TSPO 18kDa PET-imaging candidates
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1962
OP 1962
VO 50
IS supplement 2
A1 Damont, Annelaure
A1 Van Camp, Nadja
A1 Kuhnast, Bertrand
A1 Boisgard, Raphael
A1 Chauveau, Fabien
A1 Probst, Katrin
A1 Katsifis, Andrew
A1 Kassiou, Mickael
A1 Tavitian, Bertrand
A1 Dolle, Frederic
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1962.abstract
AB 1962 Objectives DPA-714, PBR111, FEDAA1106, three challengers of PK11195 for TSPO 18 kDa imaging, were labeled with fluorine-18. Comparative pharmacological evaluation was performed by autoradiography in an acute rodent model of neuroinflammation. Methods Fluorine-18-labeling has been automated on our Zymate-XP robotic system and involves: (A) reaction of K[18F]F-Kryptofix®222 with the appropriate precursor at 165°C for 5 min in DMSO, (B) C-18 PrepSep cartridge pre-purification, (C) semi-preparative HPLC purification and (4) Sep-pak®Plus-based formulation. In vitro binding properties of these labeled ligands were studied in a rat model of focal acute neuroinflammation, and were compared with the reference compound [11C]PK11195, using autoradiography. Immunohistochemistry study was performed to validate the in vitro data. Results 5-7 GBq of [18F]DPA-714, [18F]PBR111 and [18F]FEDAA1106 (> 95% chemically and radiochemically pure) could be obtained with SRA ranging from 37 to 111 GBq/micromol within 90 minutes starting from a 37 GBq [18F]fluoride batch. Radiotracer localisation as detected by autoradiography correlated well with that activated microglial cells demonstrated by immunohistochemistry and TSPO 18kDa expression. Conclusions [18F]DPA-714, [18F]PBR111, [18F]FEDAA1106 were synthesized in 8%-20% ndc radiochemical yield. Autoradiography studies confirm their potential for TSPO 18kDa expression imaging Research Support Supported by the EC DiMI (LSHB-CT-2005-512146) and EMIL (LSH-2004-503569). Thanks’ to J. Clark (Univ. Edinburgh).