title: An improved synthesis of NHS-MAG3 for conjugation and radiolabeling of biomolecules with (99m)Tc at room temperature.
abstract: The mercaptoacetyltriglycine (MAG3) chelator has been shown to stably complex technetium-99m (99mTc) for nuclear imaging and radiorhenium (186/188Re) for tumor radiation therapy studies. The bifunctional N-hydroxysuccinimidyl ester of MAG3 with S-acetyl protection (N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycinate (NHS-MAG3)) has been successfully used to covalently conjugate a MAG3 chelator to primary amine functionalized biomolecules. We describe herein a simplified synthesis of NHS-MAG3 that begins with the preparation of the N-hydroxysuccinimidyl ester of S-acetylmercaptoacetic acid (N-succinimidyl S-acetylmercaptoacetate (SATA)) from mercaptoacetic acid and is followed by the synthesis of S-acetylmercaptoacetyltriglycine from SATA, together requiring about 14 days. Finally, the synthesis of NHS-MAG3 from S-acetylmercaptoacetyltriglycine requires a further 5 days. We had earlier described a method for the preparation of MAG3-conjugated and 99mTc-radiolabeled biomolecules that required elevated temperatures during postconjugation purification. We now report a modified method for the preparation that is accomplished at room temperature and therefore applicable to temperature-sensitive biomolecules. The conjugation and radiolabeling of bovine serum albumin is used as an example. The conjugation and purification requires about 2-3 h and the radiolabeling and postlabeling purification requires about an additional 2 h.
authors: Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. yi.wang@umassmed.edu
authors: Yi
authors: Y
authors: Wang
authors: Xinrong
authors: X
authors: Liu
authors: Donald J
authors: DJ
authors: Hnatowich
mesh_terms: D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D007553:Isotope Labeling / Q000379:methods*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D015609:Organotechnetium Compounds / Q000302:isolation & purification; D012709:Serum Albumin / Q000302:isolation & purification; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013388:Succinimides / Q000138:chemical synthesis* / Q000737:chemistry; D013440:Sulfides / Q000138:chemical synthesis; D013667:Technetium / Q000737:chemistry; D013696:Temperature
chemical_list: D002614:Chelating Agents; D009842:Oligopeptides; D015609:Organotechnetium Compounds; C118517:S-acetylmercaptoacetyltriglycine N-hydroxysuccinimide; D012709:Serum Albumin; D013388:Succinimides; D013440:Sulfides; C107869:technetium Tc 99m serum albumin; D012710:Serum Albumin, Bovine; D013667:Technetium; C039011:N-hydroxysuccinimide S-acetylthioacetate