title: 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.
abstract: A novel hexa aza cage, N(1)-(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 (1)H NMR and electrospray mass spectrometry. A new method for the synthesis of the related N(1)-(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 Cu(2+), Co(2+) and Zn(2+) 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 Cu(2+) doped (64)Cu 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 (67)Cu.
authors.affiliation: Centre for Antimatter-Matter Studies (CAMS), Australian Nuclear Science and Technology Organisation (ANSTO), Menai, NSW 2234, Australia. suzanne @bnl.gov.
authors.forename: Eskender
authors.initials: E
authors.lastname: Mume
authors.forename: Ali
authors.initials: A
authors.lastname: Asad
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Di Bartolo
authors.forename: Linggen
authors.initials: L
authors.lastname: Kong
authors.forename: Christopher
authors.initials: C
authors.lastname: Smith
authors.forename: Alan M
authors.initials: AM
authors.lastname: Sargeson
authors.forename: Roger
authors.initials: R
authors.lastname: Price
authors.forename: Suzanne V
authors.initials: SV
authors.lastname: Smith
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D003301:Copper Radioisotopes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011506:Proteins / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000627:therapeutic use*; D012822:Silicon Dioxide / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: D001372:Aza Compounds; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D011506:Proteins; D019275:Radiopharmaceuticals; D003035:Cobalt; D012822:Silicon Dioxide; D003300:Copper; D015032:Zinc