New chemical and radiochemical routes to [18F]Rho6G-DEG-F, a delocalized lipophilic cation for myocardial perfusion imaging with PET

Abstract

New chemical and radiochemical syntheses are described for the preparation of [¹⁸F]Rho6G-DEG-F, an ¹⁸F-labeled analogue of the fluorescent dye rhodamine 6G, which has shown promise as myocardidal perfusion imaging agent. Tosylated precursors of [¹⁸F]Rho6G-DEG-F amenable to ¹⁸F-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 C₁₈ chromatography. Manual synthesis of [¹⁸F]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 ¹⁸F-fluorination conditions (K[¹⁸F]F/K₂CO₃/Kryptofix 2.2.2.). Incorporation of the [¹⁸F]F⁻ was found to be satisfactory (≥34% by TLC), despite the protic character of the precursor molecules. [¹⁸F]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 (n = 3) decay corrected to start-of-synthesis, >99% radiochemical purity, and a molar activity of 122–267 GBq μmol⁻¹ (3.3–7.2 Ci μmol⁻¹).