Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles

• Published in: Oncotarget 2016-05, Vol.7 (22), p.32866-32875
• Main Authors: Blanco, Víctor M, Chu, Zhengtao, LaSance, Kathleen, Gray, Brian D, Pak, Koon Yan, Rider, Therese, Greis, Kenneth D, Qi, Xiaoyang
• Format: Article
• Language: English
• Subjects: Animals; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation; Female; Fluorescent Dyes - administration & dosage; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - pharmacokinetics; Glioblastoma - diagnostic imaging; Glioblastoma - pathology; Heterografts; Humans; Luminescent Measurements; Mice, Nude; Multimodal Imaging - methods; Nanoparticles; Optical Imaging - methods; Phosphatidylserines - administration & dosage; Phosphatidylserines - chemical synthesis; Phosphatidylserines - pharmacokinetics; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Research Paper; Saposins - administration & dosage; Saposins - chemical synthesis; Saposins - pharmacokinetics; Tissue Distribution; Tumor Burden
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.8763

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.