Molecular imaging of cell death in vivo by a novel small molecule probe

Revital Aloya, Anat Shirvan*, Hagit Grimberg, Ayelet Reshef, Galit Levin, Dvora Kidron, Avi Cohen, Ilan Ziv

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo.

Original languageEnglish
Pages (from-to)2089-2101
Number of pages13
JournalApoptosis : an international journal on programmed cell death
Volume11
Issue number12
DOIs
StatePublished - Dec 2006
Externally publishedYes

Keywords

  • ApoSense
  • Apoptosis
  • Cell death
  • Chemotherapy
  • Imaging

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