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

Pharm Res. 2013 Mar;30(3):878-88. doi: 10.1007/s11095-012-0929-8. Epub 2012 Dec 7.

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 T(1) contrast agent (Gd) and the positron-emitting (89)Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities.

Methods: (89)Zr 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). (89)Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized.

Results: (89)Zr-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 (89)Zr-labeling of LPs and dual PET/MR imaging properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Contrast Media* / chemistry
  • Gadolinium* / chemistry
  • Humans
  • Isotopes / chemistry
  • Liposomes* / chemistry
  • Magnetic Resonance Imaging / methods
  • Mice
  • Neuroendocrine Tumors / diagnosis*
  • Octreotide* / chemistry
  • Positron-Emission Tomography / methods
  • Receptors, Somatostatin / analysis
  • Zirconium* / chemistry

Substances

  • Contrast Media
  • Isotopes
  • Liposomes
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • Sstr2 protein, mouse
  • Gadolinium
  • Zirconium
  • Octreotide