Hexavalent lactoside labeled with [18F]AlF for PET imaging of asialoglycoprotein receptor

Abstract

Several methods have been developed to label compounds with ¹⁸F. However, in general these are laborious and require a multistep synthesis. A method based on the chelation of ¹⁸F-aluminum fluoride ([¹⁸F]AlF) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) was developed recently. The present work was aimed to radiolabel hexavalent lactoside (NOTA-HL) by [¹⁸F]AlF method for PET imaging of asialoglycoprotein receptor (ASGPR).

Methods: hexavalent lactoside was conjugated with the NOTA chelate and labeled with ¹⁸F in a one-pot method. The labeling procedure was investigated with different amounts of NOTA-HL and aluminum concentration. Radiochemical yield and radiochemical purity were determined by radio-TLC and radio-HPLC respectively. In vitro stability study of [¹⁸F]AlF-HL were carried out. PET/CT imaging of normal mice injected with [¹⁸F]AlF-NOTA-HL was performed.

Results: The Radiochemical yield of [¹⁸F]AlF-NOTA-HL was higher with more precursor and optimal Al⁺ concentration. The radiochemical purity of labeled product was >95% after purified by Sep-Pak cartridge to remove unbound [¹⁸F]AlF. The radiolabeling, including purification, was performed in 30 min [¹⁸F]AlF-NOTA-HL exhibited good in vitro stability. PET studies in normal mice revealed high specific accumulation of activity in the liver.

Conclusion: NOTA-HL could be labeled rapidly and efficiently with aqueous ¹⁸F using AlF method. [¹⁸F]AlF-NOTA-HL would provide another efficient approach for PET imaging of ASGPR.

Keywords: Aluminum fluoride; Asialoglycoprotein receptor; Hexavalent lactoside; PET; Radiofluorination.