Simple, column purification technique for the fully automated radiosynthesis of 2-¹⁸F-PD153035

Objectives Radiolabelled epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors potentially facilitate the assessment of EGFR overexpression in tumors. The aim of the study is to explore a new fully automated method for the radiosynthesis of 2-¹⁸F-PD153035 by modifying the commercial module (PET-MF-2V-IT-Ⅰ).

Methods Firstly, the 2-F-PD153035 standard sample 2-fluoro-N-(3-bromoanilino)-6,7-dimethoxyquinazolin-4-amine was synthesized,and structural identification was performed by the ESI-MS and nuclear resonance spectrometry. Secondly,The fully automated synthesis of 2-¹⁸F-PD153035 was as shown in Fig.1. Finally, the synthesized 2-¹⁸F-PD153035 was checked for clarity, colour and presence of any suspended particle.

Results 2-¹⁸F-PD153035 was synthesized by nucleophilic displacement of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline-2-trimethylammonium chloride with ¹⁸F^-. After purification on solid-phase extraction cartridges, the 2-¹⁸F-PD153035 was obtained in 20-30% radiochemical yields (decay not corrected, n=12), with more than 99% radiochemical purity. Synthesis time was less than 30min.Biodistribution and micro-PET showed that the liver and the intestines were the main site of excretion of this drug.

Conclusions This new automated synthesis technique provide high and reproducible yields that could be optimized for routine production.

Research Support The National Natural Science Foundation of China (No. 81471704), the Science and Technology Planning Project of Zhejiang Province (No.2012C33091) and Health Bureau Project of Zhejiang Province (No.2013KYA069).