Synthesis of hexa aza cages, SarAr-NCS and AmBaSar and a study of their metal complexation, conjugation to nanomaterials and proteins for application in radioimaging and therapy

Eskender Mume, Ali Asad, Nadine M. Di Bartolo, Linggen Kong, Christopher Smith, Alan M. Sargeson, Roger Price, Suzanne V. Smith

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16 Citations (Scopus)


A novel hexa aza cage, N1-(4-isothiocyanatobenzyl)-3,6,10,13,16, 19-hexaazabicyclo[6.6.6]icosane-1,8-diamine (SarAr-NCS) was synthesized in good yield and characterized by 1H NMR and electrospray mass spectrometry. A new method for the synthesis of the related N1-(4-carboxybenzyl)- 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1,8-diamine (AmBaSar) using the p-carboxybenzaldehyde is reported. The complexation of Cu2+, Co 2+ and Zn2+ by the two ligands over a range of pHs was found to be similar to the parent derivative SarAr. SarAr-NCS was conjugated to both silica particles (≈90 nm diam.) and the model B72.3 murine antibody. The SarAr-NCSN-silica particles were radiolabeled with Cu2+ doped 64Cu and the number of ligands conjugated was calculated to be an average of 7020 ligands per particle. Conjugation of SarAr-NCS to the B72.3 antibody was optimized over a range of conditions. The SarAr-NCSN-B72.3 conjugate was stored in buffer and as a lyophilized powder at 4 °C over 38 days. Its radiolabeling efficiency, stability and immunoreactivity were maintained. The development of a high yielding synthesis of SarAr-NCS should provide an entry point for a wide range of Cu and Zn radiometal PET imaging agents and potentially radiotherapeutic agents with 67Cu. © 2013 The Royal Society of Chemistry.
Original languageEnglish
Pages (from-to)14402-14410
Number of pages9
JournalDalton Transactions
Issue number40
Publication statusPublished or Issued - 28 Oct 2013
Externally publishedYes

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