New chemical and radiochemical routes to [F]Rho6G-DEG-F, a delocalized lipophilic cation for myocardial perfusion imaging with PET.

New chemical and radiochemical syntheses are described for the preparation of [F]Rho6G-DEG-F, an F-labeled analogue of the fluoresecent dye rhodamine 6G, which has shown promise as myocardidal perfusion imaging agent. Tosylated precursors of [F]Rho6G-DEG-F amenable to F-labeling were obtained either through a two-step synthesis from rhodamine 6G lactone (33% yield), or in one step from rhodamine 575 (64% yield), then purified by preparative C chromatography. Manual synthesis of [F]Rho6G-DEG-F was achieved in a single radiochemical step from either the tosylate salt or the tosylate/formate double salt in DMSO under standard nucleophillic aliphatic F-fluorination conditions (K[F]F/KCO/Kryptofix 2.2.2.). Incorporation of the [F]F was found to be satisfactory (≥34% by TLC), despite the protic character of the precursor molecules. [F]Rho6G-DEG-F was manually synthesized in final decay-corrected radiochemical yields of 11-26% (tosylate salt) and 9-21% (tosylate/formate double salt). The protocol was transferred to an automated synthesis unit, where the product was obtained in 3-9% radiochemical yield (=3) decay corrected to start-of-synthesis, >99% radiochemical purity, and a molar activity of 122-267 GBq/μmol (3.3-7.2 Ci/μmol).