Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles.
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.
Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Víctor M
VM
Blanco
Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.|Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Zhengtao
Z
Chu
Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Kathleen
K
LaSance
Molecular Targeting Technologies, Inc., West Chester, Pennsylvania 19380, USA.
Brian D
BD
Gray
Molecular Targeting Technologies, Inc., West Chester, Pennsylvania 19380, USA.
Koon Yan
KY
Pak
Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Therese
T
Rider
Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Kenneth D
KD
Greis
Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.|Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Xiaoyang
X
Qi
D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008163:Luminescent Measurements; D008819:Mice, Nude; D064847:Multimodal Imaging / Q000379:methods*; D053758:Nanoparticles; D061848:Optical Imaging / Q000379:methods*; D010718:Phosphatidylserines / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D049231:Saposins / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution; D047368:Tumor Burden
D005456:Fluorescent Dyes; D010718:Phosphatidylserines; D019275:Radiopharmaceuticals; D049231:Saposins; C042511:1,2-dioleoylphosphatidylserine
PET; SapC-DOPS; glioblastoma; liposome; optical imaging