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

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.