Molecular imaging and therapy of cancer with radiolabeled nanoparticles

Abstract

This review summarizes the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and internal radiotherapy applications targeting cancer. With the capacity to provide enormous flexibility, radiolabeled nanoparticles have the potential to profoundly impact disease diagnosis and patient management in the near future. Currently, the major challenges facing the research on radiolabeled nanoparticles are desirable (tumor) targeting efficacy, robust chemistry for both radionuclide encapsulation/incorporation and targeting ligand conjugation, favorable safety profile, as well as certain commercial and regulatory hurdles.

Figure 1

¹¹¹In-labeled ChL6 antibody was conjugated to a 20 nm dextran bead coated with polyethylene glycol and impregnated with iron oxide nanoparticles. (Reprinted with permission from [20]. ©2007 Society of Nuclear Medicine.)

Figure 2

⁶⁴Cu-labeled SWNTs for tumor integrin α_vβ₃ targeting. (a) A schematic drawing of the functionalized SWNTs. (b) Two-dimensional projection of PET images of U87MG tumor-bearing mice at 8 h after injection of ⁶⁴Cu-labeled, RGD-conjugated SWNTs with (Block) or without co-injection of RGD peptides. Arrowheads indicate tumors. (c) Raman spectra of tissue homogenate provided direct evidence of SWNT presence in the tumor. (d) Good agreement of biodistribution data obtained by PET and ex vivo Raman measurements confirmed the in vivo stability and tumor-targeting efficacy of SWNT-RGD. (Adapted with permission from [42]. ©2007 Nature Publishing Group.)

Figure 3

Dual-modality PET/NIRF imaging of integrin α_vβ₃ in tumor vasculature. (a) A schematic structure of the dual-modality PET/NIRF probe. (b) NIRF (after injection of QD-RGD) and coronal microPET (after injection of ⁶⁴Cu-DOTA-QD-RGD) images of a U87MG tumor-bearing mice. Arrowheads indicate tumors. (c) Excellent overlay between CD31 and QD fluorescence, as well as between murine β₃ and QD fluorescence, confirmed that DOTA-QD-RGD mainly targeted integrin α_vβ₃ on the tumor vasculature. (Adapted with permission from [65]. ©2007 Society of Nuclear Medicine.)

Figure 4

Dual-modality PET/MR imaging of integrin α_vβ₃. (a) A schematic illustration of the dual-modality probe. The DOTA chelator enables PET imaging after ⁶⁴Cu-labeling. (b) Coronal PET and T₂-weighted MR images of tumor-bearing mice at 4 h after injection of ⁶⁴Cu-labeled RGD-PASP-IO, PASP-IO, and RGD-PASP-IO mixed with unconjugated RGD peptides (denoted as “Block”). Prussian blue staining of the U87MG tumor tissue slices after in vivo imaging is also shown, where blue spots indicate the presence of IO nanoparticles. (Adapted with permission from [86]. ©2008 Society of Nuclear Medicine.)

Figure 5

Many types of nanoparticles have been radiolabeled for molecular imaging and therapy of cancer.

Figure 6

A multifunctional nanoplatform incorporating multiple receptor targeting, multimodality imaging, and multiple therapeutic entities. Not all functional moieties will be necessary and only suitably selected components are needed for each individual application. The various functional moieties may be either on the surface of or encapsulated inside the nanoparticle.