Nanotargeted radionuclides for cancer nuclear imaging and internal radiotherapy

Abstract

Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, alpha-, beta-, and gamma-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients.

Figure 1

(a) Schematic illustration showing the possible mechanism for radionuclides or drug accumulation delivery system of nanoparticles by site specific passive tumor targeting using the enhanced permeability and retention (EPR) effect or molecular affinity and site specific active tumor targeting through ligand tumor cell surface receptors interaction, internalization, and intracellular action for tumor diagnostics and therapy (reproduced with modification with permission from [7]). (b) Schematic diagram of tumor tissue penetration range of internal radiotherapy by auger electron (0.1–2 keV, <1 μm )-, α (5–8 MeV, 50–80 μm range)-, and β (0.1–2.2 MeV, 1–10 mm range )- radiation emitters for passively and actively nanotargeted radionuclide therapy (reproduced with modification with permission from [14]).

Figure 2

(a) Gamma scintigraphy of BALB/c mice bearing CT-26 tumor animal model at 24 hr and 48 hr after intravenous injection of passively nanotargeted radionuclides of ¹¹¹In-DTPA-liposome (reprinted with permission from reference [70]). (b) Tumor growth inhibition with passively nanotargeted radionuclides of ¹¹¹In-(VNB)-liposome on HT-29/luc tumor bearing in SCID mice animal model (reprinted with permission from reference [71]). (c) MicroSPECT/CT images of passively nanotargeted radionuclides of ¹⁸⁸Re-liposome and ¹⁸⁸Re-DXR-liposome targeting CT-26 bearing in BALB/c mice animal model at 1 h, 4 h, 24 h, and compare with the control (reprinted with permission from reference [72]). (d) Therapeutic efficacy of tumor volume change and survival ratio for CT-26 tumor-bearing BALB/c mice after intravenous administration of passively nanotargeted radionuclides of ¹⁸⁸Re-(DXR)-liposome were illustrated. (reprinted with permission from reference [73]).

Figure 2

(a) Gamma scintigraphy of BALB/c mice bearing CT-26 tumor animal model at 24 hr and 48 hr after intravenous injection of passively nanotargeted radionuclides of ¹¹¹In-DTPA-liposome (reprinted with permission from reference [70]). (b) Tumor growth inhibition with passively nanotargeted radionuclides of ¹¹¹In-(VNB)-liposome on HT-29/luc tumor bearing in SCID mice animal model (reprinted with permission from reference [71]). (c) MicroSPECT/CT images of passively nanotargeted radionuclides of ¹⁸⁸Re-liposome and ¹⁸⁸Re-DXR-liposome targeting CT-26 bearing in BALB/c mice animal model at 1 h, 4 h, 24 h, and compare with the control (reprinted with permission from reference [72]). (d) Therapeutic efficacy of tumor volume change and survival ratio for CT-26 tumor-bearing BALB/c mice after intravenous administration of passively nanotargeted radionuclides of ¹⁸⁸Re-(DXR)-liposome were illustrated. (reprinted with permission from reference [73]).

Figure 3

In vivo actively nanotargeted radionuclides of  ⁶⁴Cu-DOTA-QD-RGD for dual-function PET and near-infrared fluorescence (NIR) imaging of U87MG tumor vasculature mice animal model. (a) PET images of ⁶⁴Cu-labeled nanoparticles of DOTA-QD or DOTA-QD-RGD. Arrow heads indicate tumors. (b) Liver uptake of ⁶⁴Cu-labeled nanoparticles of DOTA-QD or DOTA-QD-RGD. (c) U87MG tumor uptake of ⁶⁴Cu-labeled nanoparticles of DOTA-QD or DOTA-QD-RGD. (d) Two-dimensional image of the 2 mice shown in (a) at 5 hr after injection (reprinted with permission from reference [37]). DOTA: 1,4,7,10-tetraazacyclodocecane- N,  N′,N′′,N′′′- tetraacetic acid chelators for radionuclides labeling. QD: Quantum dots conjugated with NIR probe. RGD: Arginine-glycine-aspartic acid peptide for targeting tumor angiogenesis integrin α_vβ₃.