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Pre-concentration of positron-emitting [18F]fluoride and radiosynthesis of fluoride-based prosthetic compounds for PET imaging using magnetic droplet microfluidics (MDM)

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Thesis type
(Thesis) M.Sc.
Date created
The radioisotope 18F is often considered the best choice for PET imaging, owing to its desirable chemical and radiochemical properties. However, nucleophilic 18F fluorination of large, water soluble biomolecules, based on C-F bond formation, has been difficult. Thus, several aqueous fluorination approach have been developed which offers significant development in radiopharmaceutical synthesis. Furthermore, since 18F decays rapidly, production of these 18F-labelled compounds requires an automated process to reduce production time, reduce radiation exposure and also minimize transfer of reagents during tracer synthesis to reduce sample transfer loss. Herein, a method called magnetic droplet microfluidics (MDM) has been developed which aims to conduct [18F]fluoride pre-concentration and synthesis of 18F-labeled compound on a microfluidic platform. Using this method, we have demonstrated 18F pre-concentration in a small-volume droplet through the use of anion exchanging magnetic particles. By using MDM, the pre-concentration step took approximately 5 min. and the [18F]fluoride solution was pre-concentrated by 15-fold from a volume of 1 mL to 0.05 mL. After the pre-concentration step, an 18F-labelling reaction was performed on the MDM platform using the S-F bond formation in aqueous conditions to produce an arylsulfonyl [18F]fluoride which can be used as a prosthetic group to label PET targeting ligands. The high radiochemical purity of 95 ± 1% was comparable with 96% which was previously reported using conventional method. In addition, when using MDM, the total synthesis time was improved to 15 min. with lower reagent volumes (50-60 µL) used. The MDM method was also used to produce an 18F-labelled aryltrifluoroborate through B-F bond formation. The synthesis of aryltrifluoroborate compound at low activities (~5 mCi), gave radiochemical purities which were low for both MDM (5.8%) and conventional method (6.0%).
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Supervisor or Senior Supervisor
Thesis advisor: Li, Paul C.H.
Thesis advisor: Schaffer, Paul
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