A model kit for combinational 11C-reductive aminations facilitates preclinical PET screening

Objectives We believe that a 2-step radiosynthesis combining two key molecule drug features is advantageous over last step labelling in regards of preclinical screening. Thus, the main goal of this project was to extent the existing combinatorial 11C-carbonylation insertion strategy to a 2-step key motif 11C-labelling approach.

Methods For the initial key motif labelling (1st reaction), we decided to perform a simple 11C-methylation of a phenolic benzaldehyde moiety. This moiety was then reductively alkylated to various phenethylamines.

Results Ortho-, meta- and para-HBA moieties were successfully labelled and subsequently coupled to 2-CB (Scheme 1). Moreover, four diverse primary phenethylamines were coupled to 2-[11C]MB-CHO. Similar reaction parameters were observed for all conducted experiments (Scheme 1).

Conclusions We believe that the novel combinational 2-component reductive 11C-amination approach is general applicable to all kinds of key motif reductive amination strategies and leads, indeed, to an easy tracer library access.

Research Support Financial support by the Faculty of Health and Medical Sciences at the University of Copenhagen and the Lundbeck Foundation are gratefully acknowledged.