2. Academic Validation
  3. Improved synthesis of the bifunctional chelator p-SCN-Bn-HOPO

Improved synthesis of the bifunctional chelator p-SCN-Bn-HOPO

  • Org Biomol Chem. 2019 Jul 17;17(28):6866-6871. doi: 10.1039/c9ob01068h.
N V S Dinesh K Bhupathiraju 1,  Ali Younes 1,  Minhua Cao 1,  Jafar Ali 1,  Huseyin T Cicek 1,  Kathryn M Tully 2,  Shashikanth Ponnala 3,  John W Babich 3,  Melissa A Deri 4,  Jason S Lewis 2,  Lynn C Francesconi 5,  Charles Michael Drain 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Hunter College of the City University of New York, New York, New York 10065, USA. [email protected].
  • 2 Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA and Department of Radiology, the Program in Pharmacology, and the Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • 3 Radiopharmaceutical Sciences and Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
  • 4 Lehman College of the City University of New York, Bronx, New York 10468, USA and Chemistry Program, Graduate Center of the City University of New York, New York, New York 10016, USA.
  • 5 Department of Chemistry, Hunter College of the City University of New York, New York, New York 10065, USA. [email protected] and Chemistry Program, Graduate Center of the City University of New York, New York, New York 10016, USA.
PMID: 31268109 DOI: 10.1039/c9ob01068h
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 89Zr for use in radiolabeling antibodies for positron emission tomography (PET) imaging. Previous studies of 89Zr-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 89Zr. 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.

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