Microfluidic modules for pre-concentration of [¹⁸F]fluoride in positron emission tomography (PET) radiotracer synthesis

De Leonardis, Francesco

Abstract

lPositron Emission Tomography (PET) is a non-invasive imaging method which enables to obtain both molecular and biochemical information of physiological processes in vivo, which means that PET imaging shows the chemical functioning of organs and tissues in a living subject. In recent years microfluidic lab-on-a-chip devices have been explored as a promising alternative for radiotracer synthesis due to benefits such as (i) superior control over reaction conditions leading to high yields and conversion rates, (ii) reduced reagent consumption and radioactive waste production as well as (iii) potential for automation with minimised shielding requirement. That said, most devices presented so far have focused on the synthesis of the radiotracer, with relatively little emphasis on the integrated devices that perform activation, synthesis and purification steps in an automated fashion. FDG (fluorodeoxyglucose) is one of the most widely used radiopharmaceuticals in Positron Emission Tomography (PET). Moreover the availability of several other PET radionuclides makes fluorine-18 (¹⁸F) the most predominant in the fields of oncology and neuroscience.

The aim of the Radiochemistry On Chip (ROC) project was to develop such an integrated lab-on-chip device and, in particular, here results for on-chip pre-concentration of fluoride, together with some preliminary results on the removal of Kryptofix (K2.2.2) and the purification of fluoroethyl-dimethyl-2-hydroxy-ethylammonium (FECH) are presented. Here in, three microfluidic modules for fluoride pre-concentration are described, the first employs a dam structure, the second and the third magnetic forces. In the final part of the thesis, preliminary results on the purification of fluoroethylcholine (FECH) and a suitable detection method for Kryptofix (K2.2.2) are reported.

Firstly, the design, fabrication and implementation of a glass microfluidic device for recovery of [¹⁸F] and [¹⁹F]fluoride ions is described. The device was initially tested with non radioactive [¹⁹F]fluoride ions and shown to repeatedly trap and elute > 95% fluoride over 40 successive experimental runs with no decrease in efficiency. The same device was then tested for the trapping and release of [18F]fluoride ions, again over 20 experiments were executed with no measurable decrease in performance. Finally, the [¹⁸F]fluoride ions were eluted as a K¹⁸F/K2.2.2 complex, dried by repeated dissolution in acetonitrile and evaporation of residual water, and reacted with EtDT leading to the formation of the desired product ([¹⁸F]fluoroethyltosylate) with 96 ± 3 % yield (RCY). The overall time needed for conditioning, trapping, elution and regeneration was less than 6 minutes. This approach will be of great benefit towards an integrated platform able to perform faster and safer radiochemical synthesis on the micro-scale.

In the following chapter, magnetic microparticles are described as a method for the trapping and elution of [¹⁸/¹⁹F]fluoride ions via formation of a magnetic plug inside a glass microdevice. Even though the method was found to be not as fast and efficient as the packed bed of microparticles (Chapter 3), and still requires several manual steps which are time and labour consuming, the proof of principle illustrates an alternative process not yet reported in the literature, with potential for future on-chip pre-concentration of fluoride. The results showed that by employing positively charged magnetic particles, fluoride could be trapped in yield of > 50 % and elution achieved with approximately 90 % recovery of fluoride. A subsequent method for reducing the inefficiencies of the plug of magnetic particles is described where a multilaminar flow microreactor was investigated in which functionalised magnetic particles can be deflected

Citation

De Leonardis, F. (2012). Microfluidic modules for pre-concentration of [¹⁸F]fluoride in positron emission tomography (PET) radiotracer synthesis. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4214123

• Thesis Type: Thesis
• Deposit Date: May 21, 2013
• Publicly Available Date: Feb 22, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4214123
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Jan 1, 2012