A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting Journal Article


Authors: Pérez-Medina, C.; Abdel-Atti, D.; Zhang, Y.; Longo, V. A.; Irwin, C. P.; Binderup, T.; Ruiz-Cabello, J.; Fayad, Z. A.; Lewis, J. S.; Mulder, W. J. M.; Reiner, T.
Article Title: A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting
Abstract: Results: The surface chelation approach proved to be superior in terms of radiochemical yield and stability, as well as in vivo performance. Accumulation of these liposomes in tumor peaked at 24 h after injection and was measured to be 13.7 ± 1.8 percentage injected dose per gram. The in vivo performance of this probe was not essentially perturbed by the incorporation of a near-infrared fluorophore. Advances in preclinical molecular imaging have generated new opportunities to noninvasively visualize the biodistribution and tumor targeting of nanoparticle therapeutics. Capitalizing on recent achievements in this area, we sought to develop an 89Zr-based labeling strategy for liposomal nanoparticles that accumulate in tumors via passive targeting mechanisms. Methods: 89Zr-labeled liposomes were prepared using 2 different approaches: click labeling and surface chelation. Pharmacokinetic and biodistribution studies, as well as PET/CT imaging of the radiolabeled nanoparticles, were performed on a mouse model of breast cancer. In addition, a dual PET/optical probe was prepared by incorporation of a near-infrared fluorophore and tested in vivo by PET and near-infrared fluorescence imaging. Conclusion: We have developed a highly modular and efficient strategy for the labeling of liposomal nanoparticles with 89Zr. In xenograft and orthotopic mouse models of breast cancer, we demonstrated that the biodistribution of these nanoparticles can be visualized by PET imaging. In combination with a near-infrared dye, these liposomal nanoparticles can serve as bimodal PET/optical imaging agents. The liposomes target malignant growth, and their bimodal features may be useful for simultaneous PET and intraoperative imaging.
Keywords: controlled study; unclassified drug; histopathology; cancer growth; nonhuman; positron emission tomography; mouse; animal tissue; breast cancer; animal experiment; animal model; in vivo study; drug accumulation; drug distribution; drug uptake; intraoperative period; computer assisted emission tomography; radiopharmaceutical agent; drug clearance; drug half life; pet; drug tumor level; molecular probe; imaging and display; chemical procedures; liposomes; radiochemistry; mouse model; molecular stability; 89zr; female; article; near-infrared imaging; click labeled liposome zr 89; surface chelation liposome zr 89; click labeling; near infrared fluorescence imaging; surface chelation
Journal Title: Journal of Nuclear Medicine
Volume: 55
Issue: 10
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2014-10-01
Start Page: 1706
End Page: 1711
Language: English
DOI: 10.2967/jnumed.114.141861
PROVIDER: scopus
PUBMED: 25060196
PMCID: PMC4381653
DOI/URL:
Notes: Export Date: 3 November 2014 -- Source: Scopus
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  1. Jason S Lewis
    460 Lewis
  2. Valerie Ann Longo
    37 Longo
  3. Thomas Reiner
    136 Reiner
  4. Christopher P. Irwin
    10 Irwin
  5. Yachao Zhang
    8 Zhang