Radiolabeled nanoparticles for multimodality tumor imaging

Abstract

Each imaging modality has its own unique strengths. Multimodality imaging, taking advantages of strengths from two or more imaging modalities, can provide overall structural, functional, and molecular information, offering the prospect of improved diagnostic and therapeutic monitoring abilities. The devices of molecular imaging with multimodality and multifunction are of great value for cancer diagnosis and treatment, and greatly accelerate the development of radionuclide-based multimodal molecular imaging. Radiolabeled nanoparticles bearing intrinsic properties have gained great interest in multimodality tumor imaging over the past decade. Significant breakthrough has been made toward the development of various radiolabeled nanoparticles, which can be used as novel cancer diagnostic tools in multimodality imaging systems. It is expected that quantitative multimodality imaging with multifunctional radiolabeled nanoparticles will afford accurate and precise assessment of biological signatures in cancer in a real-time manner and thus, pave the path towards personalized cancer medicine. This review addresses advantages and challenges in developing multimodality imaging probes by using different types of nanoparticles, and summarizes the recent advances in the applications of radiolabeled nanoparticles for multimodal imaging of tumor. The key issues involved in the translation of radiolabeled nanoparticles to the clinic are also discussed.

Keywords: cancer; molecular imaging; multimodality imaging; radiolabeled nanoparticles; theranostics; tumor diagnosis.

Fig 1

Schematic representation of typical nano cores for the construction of radiolabeled nanoparticles.

Fig 2

(A) Schematic illustration of dual-function PET/NIRF probe DOTA-QD-RGD. PEG = polyethylene glycol. (B) Whole-body coronal PET images of mice at 1, 5, 18, and 25 h after injection of 7-14 MBq of ⁶⁴Cu-labeled DOTA-QD or DOTA-QD-RGD. Arrowheads indicate tumors. Images shown are for slices that were 1 mm thick. GI = gastrointestinal tract; L = liver. (C) Left: PET image of harvested tissues at 5 h after injection of ⁶⁴Cu-labeled DOTA-QD-RGD. Right: NIRF image of harvested tissues at 5 h after injection of ⁶⁴Cu-labeled DOTA-QD or DOTA-QD-RGD. Reprinted with the permission of the Journal of Nuclear Medicine, Cai et al., 2007.

Fig 3

(A) Schematic illustration of dual-function PET/NIRF probe DOTA-QD-VEGF. (B) Whole-body coronal PET images of U87MG tumor-bearing mice at 1, 4, 16, and 24 h post-injection of about 300 μCi of ⁶⁴Cu-DOTA-QD and ⁶⁴Cu-DOTA-QD-VEGF. Arrows indicate the tumor. (C) In vivo NIRF imaging of U87MG tumor-bearing mice at 10, 30, 60 and 90 min post-injection of 200 pmol of DOTA-QD-VEGF and DOTA-QD, respectively. Arrows indicate the tumor. Reprinted with the permission of the European Journal of Nuclear Medicine and Molecular Imaging, Chen et al., 2008.

Fig 4

(A) Control group: dual SPECT/CT and near-infrared fluorescence optical imaging of EL4 lymphoma apoptosis with ¹¹¹In-labeled annexin A5-CCPM. Mice were injected intravenously only with ¹¹¹In-labeled annexin A5-CCPM. (a) Representative SPECT/CT images. (b) Representative fluorescence molecular tomographic images. (c) Representative autoradiographs of excised tumors. (d) Fluorescence images of same slides used in autoradiographic studies. (e) and (f) Immunohistochemical staining with caspase-3 (brown) of same slides used in autoradiographic studies. All images were acquired at 48 h after injection of ¹¹¹In-labeled annexin A5-CCPM. Bar = 50 µm. (B) Chemotherapy group: dual SPECT/CT and near-infrared fluorescence optical imaging of EL4 lymphoma apoptosis with ¹¹¹In-labeled annexin A5-CCPM. Mice in chemotherapy group received intravenous injection of ¹¹¹In-labeled annexin A5-CCPM 24 h after treatment with cyclophosphamide (25 mg/kg) by intraperitoneal injection and etoposide (19 mg/kg) by intraperitoneal injection. (a) Representative SPECT/CT images. (b) Representative fluorescence molecular tomographic images. (c) Representative autoradiographs of excised tumors. (d) Fluorescence images of the same slides used in autoradiographic studies. (e) and (f) Immunohistochemical staining with caspase-3 (brown) of the same slides used in autoradiographic studies. All images were acquired 48 h after injection of ¹¹¹In-labeled annexin A5-CCPM. Bar = 50 µm. Arrows in (f) refer to the region of tumor apoptosis. Reprinted with the permission of the Journal of Nuclear Medicine, Zhang et al., 2011.

Fig 5

(A) Schematic illustration of PET/MRI probe based on iron oxide (IO) nanoparticle. (B) T2-weighted MR images of nude mice bearing U87MG tumor before injection of IO nanoparticles ((a) and (e)) and at 4 h after tail-vein injection of DOTA-IO ((b) and (f)), DOTA-IO-RGD ((c) and (g)), and DOTA-IO-RGD with blocking dose of c(RGDyK) ((d) and (h)). (C) Decay-corrected whole-body coronal PET images of nude mouse bearing human U87MG tumor at 1, 4, and 21 h after injection of 3.7 MBq of ⁶⁴Cu-DOTA-IO, ⁶⁴Cu-DOTA-IO-RGD, or ⁶⁴Cu-DOTA-IO-RGD with 10 mg of c(RGDyK) peptide per kilogram (300 µg of iron-equivalent IO particles per mouse). Reprinted with the permission of the Journal of Nuclear Medicine, Lee et al., 2008.

Fig 6

(A) Schematic illustration of the multi-funtional HSA-IONPs. (B) Representative in vivo NIRF images of mouse injected with HSA-IONPs. Images were acquired 1 h, 4 h and 18 h post injection. (C) In vivo PET imaging results of mouse injected with HSA-IONPs. Images were acquired 1 h, 4 h and 18 h post injection. (D) MRI images acquired before and 18 h post injection. Reprinted with the permission of the Biomaterials, Xie et al., 2010.

Fig 7

(A) Schematic illustration of MFR-AS1411, a cobalt-ferrite nanoparticle surrounded by fluorescent rhodamine (designated MFR) within a silica shell matrix with the AS1411 aptamer. (B) MFR-AS1411 particles were intravenously injected into tumor-bearing mice, and radionuclide images were acquired at 1, 6, and 24 h after injection. Scintigraphic images of C6 tumors in mice that received MFR-AS1411 showed that C6 tumors had accumulated MFR-AS1411 at 24 h after injection but did not accumulate MFR-AS1411mt (n = 3). Tumor growth patterns were followed using bioluminescence signals acquired from luciferase-expressing C6 cells. (C) MR images of tumor-bearing mice before and after injection of MFR-AS1411 were acquired. Dark signal intensities at tumor sites were detected in MFR-AS1411-injected mice (arrowhead). (D) Fluorescence imaging of isolated organs. Fluorescence signal at tumor site injected with MFRAS1411 was detected, compared with tumors injected with MFR-AS1411mt. Isolated organs in order from upper left to lower right were intestine, liver, spleen, muscle, fat, kidney, stomach, right tumor, left tumor, heart, lung, and tail. Reprinted with the permission of the Journal of Nuclear Medicine, Hwang et al., 2010.