¹⁷⁷Lu-Labeled Eu-Doped Mesoporous SiO₂ Nanoparticles as a Theranostic Radiopharmaceutical for Colorectal Cancer

Abstract

Colorectal cancer is one of the most significant types of cancer, ranking second in the world's mortality cases. As colorectal cancer is often diagnosed at a late stage of disease progression, effective treatments are necessary. Therefore, radiotherapy has become a fundamental approach in the treatment of colorectal cancer, especially those based on the use of 177 Lu. A potential approach to meet this challenge is the use of nanotechnology through the development of radionuclide-based nanomaterials. In this work, we investigated a SiO 2 -derived class of nanomaterials formed by the insertion of the coordination complex, based on Eu 3+ and pyrimidine-2,6-dicarboxylic acid (DPA), into nanoparticles of amino-functionalized mesoporous silica (EuDPA/SiO 2 −NH 2 ). The properties of the EuDPA/SiO 2 −NH 2 nanoparticles were initially investigated by SEM, FT-IR, TGA, and luminescence. The cellular uptake of EuDPA/SiO 2 −NH 2 nanoparticles into HT-29 cells was confirmed by fluorescence microscopy. Radioactivity was incorporated into the EuDPA/SiO 2 −NH 2 nanoparticles by replacing a tracer quantity of Eu 3+ sites with the lanthanide element 177 Lu, which resulted in the composition of a dual-modality probe for both SPECT imaging and tumor radiotherapy. Analysis of 177 Lu loading into EuDPA/SiO 2 −NH 2 particles showed efficient incorporation, up to 93% radioactivity into the final compound. The imaging potential of the 177 Lu−EuDPA/SiO 2 −NH 2 nanoparticles was investigated by SPECT/CT imaging, a subcutaneous HT-29 mouse model of colorectal cancer. Image analysis showed that tumor localization was maintained after intratumoral administration for up to 48 h. To evaluate the therapeutic potential of 177 Lu−EuDPA/SiO 2 −NH 2 nanoparticles, HT-29 xenografts were treated in vivo by direct intratumoral injection. Compared with control (PBS) treatment or treatment with unlabeled EuDPA/SiO 2 −NH 2 nanoparticles, the treatment with 177 Lu−EuDPA/SiO 2 −NH 2 nanoparticles resulted in a significantly reduced tumor growth. Together, the results of this study results indicate that 177 Lu−EuDPA/SiO 2 −NH 2 is a promising agent for further development in SPECT imaging and clinical treatment of colorectal cancer.

Radiolabeled nanomaterials for biomedical applications: radiopharmacy in the era of nanotechnology

“…In addition, both 177 Lu radiolabeling via a chelator and direct labeling provided 177 Lu-labeled NPs with good stability (> 95%) after 24 h (González-Ruíz et al 2017), 72 h (Cvjetinović et al 2021), and 96 h (Imlimthan et al 2021;Ognjanović et al 2019) of incubation in human serum at 37 °C. 177 Lu incorporation by replacing a tracer quantity of Eu 3+ in the EuDPA complex was another radiolabeling method reported (Viana et al 2020). However, with this approach long reaction times (5 h) and several purification steps are necessary.…”

Inorganic Radiolabeled Nanomaterials in Cancer Therapy: A Review

“…Instead of relying on the adsorption of radioactive species on the surface of the nanoparticles, da Silva Viana and coauthors inserted [ 177 Lu]­LuCl 3 directly into the nanoparticle material . A Eu complex (EuDPA), allowing the use of fluorescence microscopy, was mixed with [ 177 Lu]­LuCl 3 and a silica precursor to incorporate the lanthanide compounds into the matrix of silica nanoparticles, which were then functionalized with amino groups on the surface.…”

“…29 Furthermore, their optoelectronic properties offer the possibility of generating ROS, which could increase the efficiency of radiolabeled fullerenes against cancer cells. 30 For instance, Shultz et al investigated radiolabeling of the endohedral metallofullerene Lu 3 N@C 80 with 177 Lu using a modified Kratschmer−Huffman apparatus. A mixture of Lu 2 O 3 and [ 177 Lu]LuCl 3 was loaded into a drilled graphite rod used as the anode.…”

Toxicity Assessment of [177Lu]Lu−iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes

“…Lutetium-177 is today the most widely used radionuclide in peptide receptor radionuclide therapy due to its availability and nuclear properties useful for theranostic applications (physical half-life of 6.7 d, β-particle emissions with a maximum energy of 497 keV convenient for therapy, and γ-ray emissions of 208 keV, suitable for in vivo imaging) [ 17 , 18 ]. Therefore, many research manuscripts have reported the synthesis of 177 Lu-labeled metallic and polymeric nanoparticles as radiotherapeutic systems [ 19 , 20 , 21 , 22 , 23 , 24 ]. However, our group reported the synthesis of [ 177 Lu]Lu 2 O 3 nanoparticles functionalized with peptides for the first time [ 25 , 26 ].…”