Radiolabeling and comparative studies of [18F]DPA-714, [18F]PBR111 AND [18F]FEDAA1106, potent TSPO 18kDa PET-imaging candidates

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).