Dataset Information

Robust and Facile Automated Radiosynthesis of [¹⁸F]FSPG on the GE FASTlab.

ABSTRACT:

Purpose

(S)-4-(3-¹⁸F-Fluoropropyl)-ʟ-Glutamic Acid ([¹⁸F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x_C^-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [¹⁸F]FSPG production are required. Here, we report a cassette-based method to produce [¹⁸F]FSPG at high radioactivity concentrations from low amounts of starting activity.

Procedures

An automated synthesis and purification of [¹⁸F]FSPG was developed using the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [¹⁸F]FSPG and by assessing radiochemical purity using radio-HPLC. Purification of [¹⁸F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, followed by a reverse elution of [¹⁸F]FSPG in phosphate-buffered saline. Subsequently, the [¹⁸F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.

Results

The optimized protocol produced [¹⁸F]FSPG in 38.4 ± 2.6 % radiochemical yield and >96 % radiochemical purity with a molar activity of 11.1 ± 7.7 GBq/μmol. Small alterations, including the implementation of a reverse elution and an altered Hypercarb cartridge, led to significant improvements in radiotracer concentration from <10 MBq/ml to >100 MBq/ml. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [¹⁸F]Fluoride.

Conclusions

We have developed a robust and facile method for [¹⁸F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. This cassette-based method enabled the production of [¹⁸F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation.

SUBMITTER: Edwards R

PROVIDER: S-EPMC8578107 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab.

Edwards Richard R Greenwood Hannah E HE McRobbie Graeme G Khan Imtiaz I Witney Timothy H TH

Molecular imaging and biology 20210520 6

<h4>Purpose</h4>(S)-4-(3-18F-Fluoropropyl)-ʟ-Glutamic Acid ([18F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system xC-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [18F]FSPG production are required. Here, we report a cassette-based me ...[more]

PMID: 34013395

Similar Datasets

Project description:BackgroundCurrent automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative approaches are desired to produce small to moderate batches to reduce cost and the amount of reagents and radioisotope needed to produce PET tracers with high molar activity. In this work we describe the first reported microvolume method for production of [18F]Florbetaben for use in imaging of Alzheimer's disease.ProceduresThe microscale synthesis of [18F]Florbetaben was adapted from conventional-scale synthesis methods. Aqueous [18F]fluoride was azeotropically dried with K2CO3/K222 (275/383 nmol) complex prior to radiofluorination of the Boc-protected precursor (80 nmol) in 10 μL DMSO at 130 °C for 5 min. The resulting intermediate was deprotected with HCl at 90 °C for 3 min and recovered from the chip in aqueous acetonitrile solution. The crude product was purified via analytical scale HPLC and the collected fraction reformulated via solid-phase extraction using a miniature C18 cartridge.ResultsStarting with 270 ± 100 MBq (n = 3) of [18F]Fluoride, the method affords formulated product with 49 ± 3% (decay-corrected) yield,> 98% radiochemical purity and a molar activity of 338 ± 55 GBq/μmol. The miniature C18 cartridge enables efficient elution with only 150 μL of ethanol which is diluted to a final volume of 1.0 mL, thus providing a sufficient concentration for in vivo imaging. The whole procedure can be completed in 55 min.ConclusionsThis work describes an efficient and reliable procedure to produce [18F]Florbetaben in quantities sufficient for large-scale preclinical applications. This method provides very high yields and molar activities compared to reported literature methods. This method can be applied to higher starting activities with special consideration given to automation and radiolysis prevention.

Dataset Information

Robust and Facile Automated Radiosynthesis of [¹⁸F]FSPG on the GE FASTlab.

Purpose

Procedures

Results

Conclusions

Publications

Robust and Facile Automated Radiosynthesis of [<sup>18</sup>F]FSPG on the GE FASTlab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab.

Purpose

Procedures

Results

Conclusions

Publications

Robust and Facile Automated Radiosynthesis of [&lt;sup&gt;18&lt;/sup&gt;F]FSPG on the GE FASTlab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Robust and Facile Automated Radiosynthesis of [¹⁸F]FSPG on the GE FASTlab.

Robust and Facile Automated Radiosynthesis of [<sup>18</sup>F]FSPG on the GE FASTlab.