In vitro and in vivo evaluation of bifunctional bisthiosemicarbazone 64Cu-complexes for the positron emission tomography imaging of hypoxia. Academic Article uri icon

Overview

abstract

  • The copper(II) bisthiosemicarbazonato complex, copper-diacetyl-bis(N4-methylthiosemicarbazonate) (Cu-ATSM), has been used clinically as a positron emission tomography (PET) tracer for the delineation of hypoxia. Six novel, asymmetric bis(thiosemicarbazones) derived from diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-amino-3-thiosemicarbazone) (H2ATSM/A), one of which contained a nitroimidazole functionality, were radiolabeled with 64Cu (t1/2=12.7 h, beta+=19.3%). In vitro studies were performed on three of the compounds using EMT6 mammary carcinoma cells under hypoxic and normoxic conditions. All compounds displayed rapid cellular association and appreciable hypoxic selectivity with increased uptake under normoxic and hypoxic conditions when compared to 64Cu-ATSM. Biodistribution and small animal PET imaging studies were then carried out in vivo using two compounds in EMT6 tumor-bearing mice. The compounds showed high tumor uptake, but also substantial accumulation in the liver. These complexes demonstrate that H 2ATSM/A represents a novel and versatile synthetic platform that can be utilized to provide hypoxic cell selectivity through functionalization of the bisthiosemicarbazonate group.

publication date

  • April 17, 2008

Research

keywords

  • Copper Radioisotopes
  • Hypoxia
  • Radiopharmaceuticals
  • Thiosemicarbazones

Identity

PubMed Central ID

  • PMC4404635

Scopus Document Identifier

  • 43949134198

Digital Object Identifier (DOI)

  • 10.1021/jm800031x

PubMed ID

  • 18416544

Additional Document Info

volume

  • 51

issue

  • 10