期刊
PHARMACEUTICAL RESEARCH
卷 30, 期 3, 页码 878-888出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-012-0929-8
关键词
nanoparticles; octreotide; PET-MRI; targeted molecular imaging; Zr-89
资金
- Geoffrey Beene Cancer Research Center of MSKCC (JSL)
- Office of Science (BER) - U.S. Department of Energy [DE-SC0002456]
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 Zr-89 (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities. Zr-89 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). Zr-89-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized. Zr-89-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. This study demonstrated SSTr2-targeting specificity along with direct chelator-free Zr-89-labeling of LPs and dual PET/MR imaging properties.
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