Improved synthesis of the bifunctional chelator p-SCN-Bn-HOPO. Issue 28 (3rd July 2019)

• Record Type: Journal Article
• Authors: Bhupathiraju, N. V. S. Dinesh K.; Younes, Ali; Cao, Minhua; Ali, Jafar; Cicek, Huseyin T.; Tully, Kathryn M.; Ponnala, Shashikanth; Babich, John W.; Deri, Melissa A.; Lewis, Jason S.; Francesconi, Lynn C.; Drain, Charles Michael
• Is Part Of: Organic & biomolecular chemistry. Volume 17:Issue 28(2019)
• Page Start: 6866
• Page End: 6871
• Publication Date: 2019-07-03
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c9ob01068h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : An improved high yield synthesis of bifunctional HOPO ligand that enables diverse applications in biomedicine including 89 Zr PET imaging. Abstract : The bifunctional ligand p -SCN-Bn-HOPO, which has four 1, 2-hydroxypyridinone groups on a spermine backbone with an isothiocyanate linker, has been shown to be an efficient and stable chelator for Zr(iv ) and, more importantly, the radioisotope 89 Zr for use in radiolabeling antibodies for positron emission tomography (PET) imaging. Previous studies of 89 Zr-HOPO-trastuzumab in mice showed low background, good tumor to organ contrast, and very low bone uptake which show p -SCN-Bn-HOPO to be an important next-generation bifunctional chelator for radioimmunoPET imaging with 89 Zr. However, the reported synthesis of p -SCN-Bn-HOPO involves nine steps and multiple HPLC purifications with an overall yield of about 1.4%. Herein we report an improved and efficient synthesis of p -SCN-Bn-HOPO in four steps with 14.3% overall yield which will improve its availability for further biological studies and wider application in PET imaging. The new synthetic route also allows variation in linker length and chemistries which may be helpful in modifying in vivo clearance behaviors of future agents.