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
| Autor: | Eskender Mume, Alan M. Sargeson, Roger I. Price, Suzanne V. Smith, Nadine Di Bartolo, A. H. Asad, Christopher B. Smith, Linggen Kong |
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| Rok vydání: | 2013 |
| Předmět: |
Stereochemistry
chemistry.chemical_element Zinc Conjugated system Nanomaterials Inorganic Chemistry Metal chemistry.chemical_compound Organometallic Compounds Aza Compounds Molecular Structure Proteins Cobalt Hydrogen-Ion Concentration Silicon Dioxide HEXA Nanostructures Copper Radioisotopes chemistry Positron-Emission Tomography visual_art Proton NMR visual_art.visual_art_medium Radiopharmaceuticals Copper Derivative (chemistry) Nuclear chemistry Conjugate |
| Zdroj: | Dalton Transactions. 42:14402 |
| ISSN: | 1477-9234 1477-9226 |
| DOI: | 10.1039/c3dt51199e |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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