[18F]fluoromisonidazole Synthesis Method based on Solid-Phase Extraction (SPE) Purification

Cocevska, Maja and Kolevska, Katerina and Atanasova, Marija and Velickovska, Maja and Jolevski, Filip and Janevik-Ivanovska, Emilija and Angelovska, Bistra and Ugrinska, Ana (2024) [18F]fluoromisonidazole Synthesis Method based on Solid-Phase Extraction (SPE) Purification. In: 21st European Symposium on Radiopharmacy & Radiopharmaceuticals, 18-21 Apr 2024, Coimbra, Portugal.

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Abstract

Background
The fluorinated nitroimidazole derivatives with 18F radioisotope have desirable properties for imaging hypoxia. Among the PET radiopharmaceuticals selectively targeting hypoxic conditions is [18F]Fluoromisonidazole (1-[18F]fluoro-3-(2-nitro-1H-imidazol-1-yl)propan-2-ol, [18F]FMISO). To date, two methodologies have been developed for the production of [18F]FMISO. One method, considered standard, utilizes a synthesis module connected to HPLC purification unit. The second, more recently developed method involves a synthesis module with Sep-Pak solid phase extraction cartridges (SPE purification). The objective of this work was to optimize a [18F]FMISO synthesis process with SPE purification, with the objective of achieving a level of purity comparable to the well-established HPLC purification. This required modifying and optimizing the reaction conditions to maximize both yield and purity.
Materials and methods
The sequence was developed for the automated synthesis of [18F]FMISO with SPE purification, employing an existing Synthera V2 synthesis modulе. Radiosynthesis and purification were subsequently optimized for several parameters, including: initial conditions in the reaction before radiofluorination; radiofluorination reaction conditions; conditions after radiofluorination reaction; types of SPE purification cartridges: six reverse-phase cartridge, two cation-exchange cartridges and two aluminum oxide cartridge. Over 40 syntheses were carried out for this purpose, and quality control was done for each batch of product.

Results
The following conditions were identified as the most optimal in all these reactions:
- use of QMA-CO3- as the anion-exchange cartridge for [18F]F- trapping and a cryptand elution solution in which the ratio of ACN : H2O is 1 : 8;
- 5 mg of NITTP precursor, with a radiofluorination temperature of 120-130 °C and a duration of 10 minutes;
- utilizing an optimal volume for the hydrolysis solution, specifically 4 mL of 0.1 M HCl with a hydrolysis temperature of 110°C and a time of 3/4 minutes;
- choosing the most effective purification cartridges: reverse-phase cartridge Oasis HLB Light, cation exchange cartridge Maxi-Clean SCX, aluminum oxide cartridges Alumina B Plus Light.
Conclusions
Reaction conditions were successfully optimized for the synthesis of [18F]Fluoromisonidazole by SPE purification, producing a radiopharmaceutical of quality that meets all the criteria defined in the Ph. Eur. Monograph for Fluoromisonidazole (18F) injection.

Item Type:	Conference or Workshop Item (Poster)
Subjects:	Medical and Health Sciences > Other medical sciences
Divisions:	Faculty of Medical Science
Depositing User:	Maja Cocevska
Date Deposited:	18 Jun 2024 11:36
Last Modified:	18 Jun 2024 11:36
URI:	https://eprints.ugd.edu.mk/id/eprint/34295

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