Efficient synthesis of (¹⁸F) fluoroethylraclopride for dopamine D2 receptors imaging using PET

Positron Emission Tomography (PET) functional brain imaging has facilitated the diagnostics and therapeutic approaches for various neurological and neuropsychiatric disorders. (¹¹C) Raclopride is a standard PET radioligand for investigation of dopamine D2 receptor density, distribution and deficiency. However, the use of (¹¹C)Raclopride possess certain limitations like short half-life and low efficiency. These inadequacies have established the need to label raclopride with a radioisotope which could enhance its efficiency for imaging. Thus, with the aim of development of a more efficient and stable dopamine receptor binding radiotracer with longer half life, ¹⁸F labeled fluoroethylraclopride has been synthesized. The radiochemical synthesis of (¹⁸F) fluoroethylraclopride is accomplished via two steps. (¹⁸F)fluoroalkyl tosylate is prepared by (¹⁸F)fluoro substitution on ditosylate in the presence of an efficient phase-transfer catalyst Kryptofix 222. (¹⁸F) fluoroalkyl tosylate is then allowed to alkylate a secondary amine precursor to yield (¹⁸F)fluoroethylraclopride. Purification of the product is achieved in single step using HPLC. The radiochemical yield of the final product is approximately 25% (decay corrected). Animal studies also demonstrated that the maximum uptake of (¹⁸F)fluoroethylraclopride reached within 15 minutes post injection. (¹⁸F)fluoroethylraclopride has displayed increased half-life, good brain uptake, high stability and specificity. It has proved to be a potential candidate for PET imaging of dopaminergic receptors. (author)