PT  - JOURNAL ARTICLE
AU  - Carlos Pérez-Medina
AU  - Dalya Abdel-Atti
AU  - Yachao Zhang
AU  - Valerie A. Longo
AU  - Chrisopher P. Irwin
AU  - Tina Binderup
AU  - Jesús Ruiz-Cabello
AU  - Zahi A. Fayad
AU  - Jason S. Lewis
AU  - Willem J.M. Mulder
AU  - Thomas Reiner
TI  - A Modular Labeling Strategy for In Vivo PET and Near-Infrared Fluorescence Imaging of Nanoparticle Tumor Targeting
AID  - 10.2967/jnumed.114.141861
DP  - 2014 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1706--1711
VI  - 55
IP  - 10
4099  - http://jnm.snmjournals.org/content/55/10/1706.short
4100  - http://jnm.snmjournals.org/content/55/10/1706.full
SO  - J Nucl Med2014 Oct 01; 55
AB  - 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. 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. 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.