Electrophilic synthesis of [18F]UCB-J and evaluation of metabolic profile in rats
Pohja, Joonas (2024-12-03)
Electrophilic synthesis of [18F]UCB-J and evaluation of metabolic profile in rats
(03.12.2024)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
avoin
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe202501204799
https://urn.fi/URN:NBN:fi-fe202501204799
Tiivistelmä
Positron emission tomography is a technique of non-invasive imaging of a body utilizing positron emitting radionuclides. Among the many radionuclides used in positron emission tomography, fluorine-18 has proven to be extremely suitable for it due to its beneficial properties of a relatively long half-life of 109.8 minutes and low maximum positron emission energy of 635 keV. Fluorine-18 can be used in the radiolabeling of compounds via either a nucleophilic or electrophilic approach. The use of electrophilic fluorine-18 labeling has the advantage of higher reactivity while suffering from lower molar activity when compared to the nucleophilic method. Several different electrophilic 18F-fluorinating reagents have been developed to aid in the use of electrophilic fluorine-18, among them [18F]fluoro-benziodoxole.
[18F]Fluoro-benziodoxole is an electrophilic 18F-fluorinating reagent capable of the umpolung of fluorine-18. This ability allows for the combining of the nucleophilic and electrophilic methods via an inversion of polarity, by first producing fluorine-18 as a nucleophile and then converting it to an electrophilic form. Due to this fluorine-18 can be produced in high starting molar activities afforded by the nucleophilic fluorine-18 and then utilizing the high reactivity of the electrophilic form. [18F]Fluoro-benziodoxole has not been widely applied in the field radiopharmaceutical chemistry, and one of the aims of this work is to tests it in the synthesis of the radiotracer [18F]UCB-J.
[18F]UCB-J is a radiotracer for the imaging of synaptic vesicle glycoprotein 2A that has been previously used as mainly a carbon-11 labeled radiotracer but recently a fluorine-18 labeled version has also been developed. In addition to testing the use [18F]fluoro-benziodoxole for the synthesis of [18F]UCB-J, this work also includes a study of the radiometabolism of [18F]UCB-J using rats as test animals.
When comparing the results of the [18F]fluoro-benziodoxole synthesis of [18F]UCB-J to the reference HPLC chromatogram, no produced [18F]UCB-J could be detected. This shows that the [18F]fluoro-benziodoxole synthesis of [18F]UCB-J does not work. The analyzed results of the radiometabolism study of [18F]UCB-J were analyzed by reverse and normal phase radioTLC and radioHPLC. The results of the radiometabolism study show large degrees of radiometabolism in the liver and plasma of the test animals while showing the least radiometabolism in the brain and liver of the test animals. In addition to this the reverse phase radioTLC method afforded better separation of radiometabolites than the normal phase radioTLC method.
Though the synthesis of [18F]UCB-J via the [18F]fluoro-benziodoxole method was not successful, [18F]fluoro-benziodoxole should not be ruled out as an electrophilic 18F-fluorinating reagent. Further testing is required to chart the full potential uses of [18F]fluoro-benziodoxole in the field of fluorine-18 radiolabeling chemistry.
[18F]Fluoro-benziodoxole is an electrophilic 18F-fluorinating reagent capable of the umpolung of fluorine-18. This ability allows for the combining of the nucleophilic and electrophilic methods via an inversion of polarity, by first producing fluorine-18 as a nucleophile and then converting it to an electrophilic form. Due to this fluorine-18 can be produced in high starting molar activities afforded by the nucleophilic fluorine-18 and then utilizing the high reactivity of the electrophilic form. [18F]Fluoro-benziodoxole has not been widely applied in the field radiopharmaceutical chemistry, and one of the aims of this work is to tests it in the synthesis of the radiotracer [18F]UCB-J.
[18F]UCB-J is a radiotracer for the imaging of synaptic vesicle glycoprotein 2A that has been previously used as mainly a carbon-11 labeled radiotracer but recently a fluorine-18 labeled version has also been developed. In addition to testing the use [18F]fluoro-benziodoxole for the synthesis of [18F]UCB-J, this work also includes a study of the radiometabolism of [18F]UCB-J using rats as test animals.
When comparing the results of the [18F]fluoro-benziodoxole synthesis of [18F]UCB-J to the reference HPLC chromatogram, no produced [18F]UCB-J could be detected. This shows that the [18F]fluoro-benziodoxole synthesis of [18F]UCB-J does not work. The analyzed results of the radiometabolism study of [18F]UCB-J were analyzed by reverse and normal phase radioTLC and radioHPLC. The results of the radiometabolism study show large degrees of radiometabolism in the liver and plasma of the test animals while showing the least radiometabolism in the brain and liver of the test animals. In addition to this the reverse phase radioTLC method afforded better separation of radiometabolites than the normal phase radioTLC method.
Though the synthesis of [18F]UCB-J via the [18F]fluoro-benziodoxole method was not successful, [18F]fluoro-benziodoxole should not be ruled out as an electrophilic 18F-fluorinating reagent. Further testing is required to chart the full potential uses of [18F]fluoro-benziodoxole in the field of fluorine-18 radiolabeling chemistry.