Automated synthesis of F-18-labeled rhodamine 6G

Objectives We previously demonstrated that F-18-labeled rhodamine 6G is a promising agent for myocardial perfusion imaging. To date, however, all syntheses have been carried out manually. The objective of this study was, therefore, to develop an automated synthesis of F-18-labeled rhodamines.

Methods The Advion Nanotek microfluidic system was used to automate the two-step synthesis. In the first step, the diethylene glycol prosthetic group was labeled with F-18. The second step involved a novel configuration of the system in which the labeled prosthetic group was delivered to the solid rhodamine lactone in a second concentrator rather than using the microreactor. This approach was necessary because of the low solubility of the precursor in acetonitrile, etc. The reaction mixture was then heated (120 Deg, 20 min) to accomplish labeling. The crude product was purified by semi-prep HPLC.

Results F-18 labeled rhodamine 6G was synthesized by using a novel configuration of the NanoTek microfluidic system. The radiochemical yield of the automated synthesis is ~25%, similar to the manual synthesis (30%). The automated reaction, including F-18 drying, takes about 45 min, somewhat shorter than the manual synthesis time (60min). For the automated synthesis, post-synthesis procedures, such as resolubilization and filtration of the final reaction mixture were also programmed into the system. An additional advantage is reduced radiation exposure to laboratory personnel.

Conclusions In this study, we established an automated microfluidic method for the two-step synthesis of F-18-labeled rhodamine 6G. The automated synthesis provides good radiochemical yield and shortened synthesis time while reducing radiation exposure compared with the manual synthesis method.

Research Support 5R01HL108107, Children’s Hospital Radiology Foundation