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.
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Abbreviations
- CL:
-
control-liposome
- CT:
-
computed tomography
- LP:
-
liposome
- MRI:
-
magnetic resonnance imaging
- OCT:
-
octreotide
- OL:
-
octreotide-liposome
- PEG:
-
polyethylene glycol
- PET:
-
positron emission tomography
- SPECT:
-
single-photon emission computed tomography
- SSTr2:
-
somatostatin receptor subtype 2
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ACKNOWLEDGMENTS AND DISCLOSURES
This work was funded in part by the Geoffrey Beene Cancer Research Center of MSKCC (JSL), the Office of Science (BER) - U.S. Department of Energy (Award DE-SC0002456; JSL). We thank Drs. Grimm, Blasberg, Pillarsetty, McDevitt and Le for their insights. We also acknowledge support provided by Mr. William H., Mrs. Alice Goodwin, the Commonwealth Foundation for Cancer Research and The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center. Finally, we would like to thank technical services provided by the MSKCC Small-Animal Imaging Core Facility.
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Supplementary Material
LP purification, labeling efficiency, in vitro experiment, maximum intensity projection PET images, histology and autoradiography of tumors, as well as 24 and 96 h p.i. radioactive tissue distribution are included in supplementary material. (DOC 216 kb)
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Abou, D.S., Thorek, D.L.J., Ramos, N.N. et al. 89Zr-Labeled Paramagnetic Octreotide-Liposomes for PET-MR Imaging of Cancer. Pharm Res 30, 878–888 (2013). https://doi.org/10.1007/s11095-012-0929-8
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DOI: https://doi.org/10.1007/s11095-012-0929-8