89Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer

Diane S. Abou, Daniel L.J. Thorek, Nicholas N. Ramos, Martijn W.H. Pinkse, Hubert T. Wolterbeek, Sean D. Carlin, Bradley J. Beattie, Jason S. Lewis

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Purpose: Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T1 contrast agent (Gd) and the positron-emitting 89Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities. Methods: 89Zr oxophilicity was unexpectedly found advantageous for direct radiolabeling of preformed paramagnetic LPs. LPs were conjugated with octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2). 89Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized. Results: 89Zr-LPs showed reasonable stability over serum proteins and chelator challenges for proof-of-concept in vitro and in vivo investigations. Nuclear and paramagnetic tracking quantified superior SSTr2-recognition of octreotide-LP compared to controls. Conclusions: This study demonstrated SSTr2-targeting specificity along with direct chelator-free 89Zr-labeling of LPs and dual PET/MR imaging properties.

Original languageEnglish
Pages (from-to)878-888
Number of pages11
JournalPharmaceutical Research
Volume30
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Keywords

  • PET-MRI
  • Zr
  • nanoparticles
  • octreotide
  • targeted molecular imaging

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