Abstract View

Objectives: Alzheimer’s disease (AD) remains one of the most devastating neurodegenerative disorders, with 10 million new cases reported every year. Early diagnosis remains challenging and could be vastly improved using Positron Emission Tomography (PET) purpose-designed sensitive radiotracers. In this prospect, Monoamine Oxidase-B (MAO-B) is emerging as a promising target due to its upregulation in the early stages of AD neuroinflammation.¹ [¹⁸F]SMBT-1 was developed as MAO-B PET radiotracer but lacks a robust, cGMP production process.² Herein we propose a fully automated process suitable for routine production and clinical translation of [¹⁸F]SMBT-1.

Methods: The automated production process was developed on a Trasis AllinOne equipped with a Luna (2) C18 semi-preparative HPLC column and adapting standard cassette and reagents available off-the-shelf from Trasis. Briefly, [¹⁸F]fluoride in H₂[¹⁸O]O (0.2–40 GBq) was trapped on a QMA cartridge and eluted with tetrabutylammonium bicarbonate. After azeotropic drying, the in-house developed SMBT-1 precursor diluted in DMSO was added and the reaction was heated to 120 °C for 7 min. After a rapid HCl deprotection, the product was purified by HPLC in a mixture of ethanol/water. The collected fraction (Rt ≈ 12 min) was diluted with sodium ascorbate in water for injection and sterile filtered to yield formulated [¹⁸F]SMBT-1 ready for use. QC of the final product was carried out according to guidelines.

Figure 1. A] Reagent and conditions: i) [¹⁸F]F^-, TBAHCO₃, DMSO, 120 °C, 7 min; ii) Aq. HCl 2M, 100 °C, 1 min. B] Representative chromatogram of [¹⁸F]SMBT-1 semi-preparative HPLC purification. C] Process performance.

Results: Formulated [¹⁸F]SMBT‑1 was obtained in 39±2% (n = 3) activity yield and with a total production time of 44±1 min. QC of the final product was within standard Eu. Ph. and ICH(Q3) specifications, radiochemical purity was ≥ 98%, enantiomeric purity ≥ 96%, and chemical purity 0.54±0.6 µg.mL^-1. The process was tested up-to a starting activity of 40 GBq resulting in a molar activity of 364-476 GBq.µmol^-1 (n = 2).

Conclusion: We have developed and optimized a robust, reliable and cGMP-ready automated radiosynthesis of [¹⁸F]SMBT-1 on the Trasis AllinOne platform using commercially available kits and cassette. The method provides the target radiotracer in excellent activity yields, high purity and in a formulation suitable for human injection, ready for further evaluation in clinical trials.

¹ Acta Neuropathol. 2024, 147 (1), 66.

² J. Nucl. Med. 2022, 63 (10), 1551–1559