Gallium-68 and scandium-44 labelled radiotracers based on curcumin structure linked to bifunctional chelators: Synthesis and characterization of potential PET radiotracers.

Author(s) Orteca, G.; Sinnes, J.P.; Rubagotti, S.; Iori, M.; Capponi, P.Cesare; Piel, M.; Rösch, F.; Ferrari, E.; Asti, M.
Journal J Inorg Biochem
Date Published 2019 Dec 05

Curcumin metal complexes showed widespread applications in medicine and can be exploited as a lead structure for developing new tracers for nuclear medicine application. Herein, the synthesis, chemical characterization and radiolabelling with gallium-68 and scandium-44 of two new targeting vectors based on curcumin scaffolds and linked to the chelators 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) and 1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-methylperhydro-1,4-diazepine (AAZTA) are reported. Synthesis of the precursors could be achieved with a 13% and 11% yield and radiolabelling generally afforded rapid incorporation under mild conditions (>95%). Stability in physiological media (~75% after 2 h in human blood for [Ga]Ga-/[Sc]Sc-AAZTA-PC21 and ~60% for [Ga]Ga-NODAGA-C21, respectively) are generally enhanced if compared to the previously radiolabelled analogues. MS fragmentation experiments showed high stability of the AAZTA-PC21 structure mainly due to the pyrazole derivatization of the curcumin keto-enol moiety and a more feasible radiolabelling was noticed both with gallium-68 and scandium-44 mainly due to the AAZTA-chelator properties. [Ga]Ga-NODAGA-C21 showed the most favorable lipophilicity value (logD = 1.3). Due to these findings, both compounds appear to be promising candidates for the imaging of colorectal cancer, but further studies such as in vitro uptake and in vivo biodistribution experiments are needed.

DOI 10.1016/j.jinorgbio.2019.110954
ISSN 1873-3344
Citation J Inorg Biochem. 2019;204:110954.