A general [<sup>18</sup>F]AlF radiochemistry procedure on two automated synthesis platforms

Allott, Louis; Pieve, Chiara Da; Turton, David R.; Smith, Graham

doi:10.1039/c6re00204h

Cited by 25 publications

(30 citation statements)

References 25 publications

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“…These promising preclinical results, the commercial availability of the precursor (GMP-grade) and the straightforward radiolabeling strategy, make [ 18 F]AlF-NOTA-octreotide an ideal candidate for imaging NET in a clinical setting. Allott et al described recently a general Al 18 F-radiochemistry procedure on two automated radiosynthetizer platforms (Trasis AllinOne® and GE TRACERlab FX FN ) and concluded that both systems have a great potential for the GMP productions of Al 18 F radiopharmaceuticals (Allott et al 2017). They successfully produced [ 18 F]AlF-NOTAoctreotide using this procedure but further optimization was required for routine clinical GMP production.…”

Section: Introductionmentioning

confidence: 99%

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Tshibangu

Cawthorne

Serdons

et al. 2020

EJNMMI radiopharm. chem.

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Background: Gallium-68 labeled synthetic somatostatin analogs for PET/CT imaging are the current gold standard for somatostatin receptor imaging in neuroendocrine tumor patients. Despite good imaging properties, their use in clinical practice is hampered by the low production levels of 68 Ga eluted from a 68 Ge/ 68 Ga generator. In contrast, 18 F-tracers can be produced in large quantities allowing centralized production and distribution to distant PET centers. [ 18 F]AlF-NOTA-octreotide is a promising tracer that combines a straightforward Al 18 F-based production procedure with excellent in vivo pharmacokinetics and specific tumor uptake, demonstrated in SSTR2 positive tumor mice. However, advancing towards clinical studies with [ 18 F]AlF-NOTA-octreotide requires the development of an efficient automated GMP production process and additional preclinical studies are necessary to further evaluate the in vivo properties of [ 18 F]AlF-NOTA-octreotide. In this study, we present the automated GMP production of [ 18 F]AlF-NOTA-octreotide on the Trasis AllinOne® radio-synthesizer platform and quality control of the drug product in accordance with GMP. Further, radiometabolite studies were performed and the pharmacokinetics and biodistribution of [ 18 F]AlF-NOTA-octreotide were assessed in healthy rats using μPET/MR. Results: The production process of [ 18 F]AlF-NOTA-octreotide has been validated by three validation production runs and the tracer was obtained with a final batch activity of 10.8 ± 1.3 GBq at end of synthesis with a radiochemical yield of 26.1 ± 3.6% (dc), high radiochemical purity and stability (96.3 ± 0.2% up to 6 h post synthesis) and an apparent molar activity of 160.5 ± 75.3 GBq/μmol. The total synthesis time was 40 ± 3 min. Further, the quality control was successfully implemented using validated analytical procedures. Finally, [ 18 F]AlF-NOTA-octreotide showed high in vivo stability and favorable pharmacokinetics with high and specific accumulation in SSTR2expressing organs in rats. Conclusion: This robust and automated production process provides high batch activity of [ 18 F]AlF-NOTA-octreotide allowing centralized production and shipment of the compound to remote PET centers. Further, the production process and quality control developed for [ 18 F]AlF-NOTA-octreotide is easily implementable in a clinical setting and the tracer is a potential clinical alternative for somatostatin directed 68 Ga labeled peptides obviating the need for a 68 Ge/ 68 Ga-generator. Finally, the favorable in vivo properties of [ 18 F]AlF-NOTA-octreotide in rats, with high and specific accumulation in SSTR2 expressing organs, supports clinical translation.

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Section: Introductionmentioning

confidence: 99%

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Tshibangu

Cawthorne

Serdons

et al. 2020

EJNMMI radiopharm. chem.

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“…A recent publication from the group describes full process automation of the approach, having been encouraged by the results of the method and the recognised requirement for automated processes in GMP production . High temperatures and a water‐miscible solvent were, again, used in the fully automated procedure which resulted in efficient radiolabelling of 2 model APPs which required single SPE‐purification of the final radiolabelled product . A clear advantage of the approach is the simplicity of the single‐vial method and ability to use commercially available aqueous [ 18 F]fluoride/H 2 O.…”

Section: Non‐site‐specific Radiolabellingmentioning

confidence: 99%

“…A clear advantage of the approach is the simplicity of the single‐vial method and ability to use commercially available aqueous [ 18 F]fluoride/H 2 O. Application of the fully automated approach to a NOTA‐derivatised octreotide, chosen for its commercial availability, achieved RCY of >45% and RCP measurements of >98% within 26 minutes …”

Section: Non‐site‐specific Radiolabellingmentioning

confidence: 99%

“…Encouraging features of fluoride acceptor chemistries have emphasised their appeal and highlighted their potential as attractive alternatives to click‐chemistry based approaches . Full process automation of an ([ 18 F]AlF) 2+ radiolabelling method and the development of single‐vial methods using lyophilized APPs are key developments in the approach that enhance the ease with which the methods can be translated to GMP. The ability to use commercially available aqueous [ 18 F]fluoride and removal of azeotropic drying steps simplify the overall procedure and increase the ease at which the methods can be implemented in a clinical setting.…”

Section: Non‐site‐specific Radiolabellingmentioning

confidence: 99%

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A review of approaches to ¹⁸F radiolabelling affinity peptides and proteins

Morris

Fairclough

Grigg³

et al. 2018

Labelled Comp Radiopharmac

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Affinity peptide and protein- (APP) based radiotracers are an increasingly popular class of radiotracer in positron emission tomography (PET), which was once dominated by the use of small molecule radiotracers. Radiolabelled monoclonal antibodies (mAbs) are important examples of APPs, yet a preference for smaller APPs, which exhibit fast pharmacokinetics and permit rapid PET aided diagnosis, has become apparent. F exhibits favourable physical characteristics for APP radiolabelling and has been described as an ideal PET radionuclide. Notwithstanding, F radiolabelling of APP is challenging, and this is echoed in the literature where a number of diverse approaches have been adopted. This review seeks to assess and compare the approaches taken to F APP radiolabelling with the intention of highlighting trends within this expanding field. Generic themes have emerged in the literature, namely the use of mild radiolabelling conditions, a preference of site-specific methodologies with an impetus for short, automated procedures which produce high-yielding [ F]APPs.

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“…As an example, a plug-and-play radiosynthesis platform accompanied by computer software based on modular subunits can easily and flexibly be configured to implement a diverse range of radiosynthesis protocols [194]. Using such systems, the standard procedures ( 18 F-labelling, hydrolysis and purification) have been implemented for many clinically relevant 18 F-tracers [103,105,191,[195][196][197] or 18 Flabelled building blocks for labelling of macromolecules [198][199][200] and build-up syntheses [145].…”

Section: Automation Of Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

18F-labelling innovations and their potential for clinical application

Coenen

Neumaier

2018

Clin Transl Imaging

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An impressive variety of new methodologies for the preparation of 18 F-labelled tracers and ligands has appeared over the last decade. Most strategies of the newly developed radiofluorination methods predominantly aim at products of high molar activity by 'late-stage' labelling of small (hetero)aromatic molecules and the use of transition metals. This is accompanied by the improvement of technical procedures, like preparation of reactive [ 18 F]fluoride and automated syntheses. The newly introduced procedures reflect a high innovative level and creativity in radio(pharmaceutical) chemistry at present, which are based on modern chemical methods and deep mechanistic insights. Taking also automation and quality control into consideration, major recently developed radiofluorination methods, most of those still under development, are compiled here in view of their potential for clinical PET imaging and thus the ability to advance molecular imaging.

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A general [¹⁸F]AlF radiochemistry procedure on two automated synthesis platforms

Abstract: The first general [18F]AIF automated radiolabelling procedure developed on the GE Tracerlab FX FN (Left) and Trasis AllInOne (Right) platforms.

Cited by 25 publications

References 25 publications

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

A review of approaches to ¹⁸F radiolabelling affinity peptides and proteins

18F-labelling innovations and their potential for clinical application

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A general [18F]AlF radiochemistry procedure on two automated synthesis platforms

Abstract: The first general [18F]AIF automated radiolabelling procedure developed on the GE Tracerlab FX FN (Left) and Trasis AllInOne (Right) platforms.

Cited by 25 publications

References 25 publications

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

A review of approaches to 18F radiolabelling affinity peptides and proteins

18F-labelling innovations and their potential for clinical application

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Product

Resources

About

A general [¹⁸F]AlF radiochemistry procedure on two automated synthesis platforms

A review of approaches to ¹⁸F radiolabelling affinity peptides and proteins