Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles
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Víctor M. Blanco1, Zhengtao Chu1,2, Kathleen LaSance3, Brian D. Gray4, Koon Yan Pak4, Therese Rider5, Kenneth D. Greis5, Xiaoyang Qi1,2
1Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
2Division of Human Genetics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA
3Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
4Molecular Targeting Technologies, Inc., West Chester, Pennsylvania 19380, USA
5Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
Xiaoyang Qi, email: [email protected]
Keywords: glioblastoma, liposome, PET, optical imaging, SapC-DOPS
Abbreviations: SapC, Saposin C; DOPS, dioleylphosphatidylserine; PS, phosphatidylserine
Received: June 25, 2015 Accepted: March 28, 2016 Published: April 16, 2016
Multimodal tumor imaging with targeted nanoparticles potentially offers both enhanced specificity and sensitivity, leading to more precise cancer diagnosis and monitoring. We describe the synthesis and characterization of phenol-substituted, lipophilic orange and far-red fluorescent dyes and a simple radioiodination procedure to generate a dual (optical and nuclear) imaging probe. MALDI-ToF analyses revealed high iodination efficiency of the lipophilic reporters, achieved by electrophilic aromatic substitution using the chloramide 1,3,4,6-tetrachloro-3α,6α-diphenyl glycoluril (Iodogen) as the oxidizing agent in an organic/aqueous co-solvent mixture. Upon conjugation of iodine-127 or iodine-124-labeled reporters to tumor-targeting SapC-DOPS nanovesicles, optical (fluorescent) and PET imaging was performed in mice bearing intracranial glioblastomas. In addition, tumor vs non-tumor (normal brain) uptake was compared using iodine-125. These data provide proof-of-principle for the potential value of SapC-DOPS for multimodal imaging of glioblastoma, the most aggressive primary brain tumor.
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