Synthesis, chemical and biochemical characterization of Lu2O3-iPSMA nanoparticles activated by neutron irradiation

Ancira-Cortez, Alejandra; Ferro-Flores, Guillermina; Jiménez-Mancilla, Nallely; Morales-Ávila, Enrique; Trujillo-Benítez, Diana; Ocampo‐García, Blanca; Santos-Cuevas, Clara; Escudero-Castellanos, Alondra; Luna-Gutiérrez, Myrna

doi:10.1016/j.msec.2020.111335

Cited by 13 publications

(22 citation statements)

References 42 publications

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“…Nevertheless, the iFAP ligand has the ability to detect with a high sensitivity, the expression of the FAP in the tumor microenvironment. Therefore, the coupling of several iFAP molecules on the surface of lutetium oxide nanoparticles activated by neutron irradiation ( 177 Lu 2 O 3 -iFAP nanoparticles) would make it possible to have a stable colloidal solution for potential therapeutic applications, as we previously reported for 177 Lu 2 O 3 -iPSMA [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…As a qualitative evidence of iFAP recognition by FAP expressed in N30 cells, the iFAP ligand was incubated for 30 min at 37 °C with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA, Macrocyclics USA, Co., Plano, TX, USA) to be covalently attached on the surface of lutetium oxide nanoparticles (Lu 2 O 3 -iFAP colloidal solution) through DOTA groups. The nanoparticle size was determined by DLS and the DOTA conjugation was confirmed by FT-IR spectroscopy, as we previously reported [ 32 ]. N30 cells were then incubated with Lu 2 O 3 -iFAP or Lu 2 O 3 (2 h at 37 °C), fixed in acetone and washed with PBS, followed by the addition of Hoechst (DNA stain, 250 μL,1μg/mL, and rinsed with PBS) to be observed in an epifluorescent microscopic field of 40×.…”

Section: Methodsmentioning

confidence: 99%

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Design, Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging

et al. 2022

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Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. 68Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl2 for labeling with 99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, 1H–NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The 99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the 99mTc-iFAP.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging

et al. 2022

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“…57 The addition of these nanoparticles was intended to trigger oxygen generation within cancer cells and thus overcome hypoxia and enhance the therapeutic efficacy. MnO 2 nanoparticles were formed in situ during the reduction of GO to rGO through the addition of KMnO 4 and a borane morpholine complex, while the chloramine-T-mediated oxidation of 131 I was used to radiolabel rGO-MnO 2 -PEG. Similar to previously reported results, a biodistribution study in 4T1 tumor-bearing mice indicated uptake not only in the tumor but also in the liver, spleen, and lung.…”

Section: Radiolabeled Nanomaterials As Therapeutic Agentsmentioning

confidence: 99%

“…AuNPs also allow the use of combined therapy strategies by using multifunctional nanoparticles. As an example, PEGcoated Au nanorods were radiolabeled with 131 I as a combined radio-and photothermal therapy agent (Figure 15a). 13 Nanorods were prepared by using cetyltrimethylammonium bromide as a ligand, followed by iodination.…”

Section: Radiolabeled Nanomaterials As Therapeutic Agentsmentioning

confidence: 99%

Inorganic Radiolabeled Nanomaterials in Cancer Therapy: A Review

Lemaître

Burgoyne

Ooms

et al. 2022

ACS Appl. Nano Mater.

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Cancer, one of the leading causes of death worldwide, remains a challenge to treat. Over the last decades, targeted therapies have emerged as a way to selectively target and treat the affected cells, leaving the healthy ones intact. Nanomaterials, with their high surface area, ease of functionalization, and interesting physicochemical properties, are seen as promising carriers for therapeutic radionuclides. Their optical, electronic, and magnetic properties can be supplemented by the emitted ionizing radiation to form theranostic (therapeutic and diagnostic) or combined therapeutic agents. This review describes how different relevant therapeutic radionuclides can be incorporated into inorganic nanoconstructs to be delivered to the cancer cells and their impact on tumors. Different types of nanomaterials as well as multiple ways of incorporating radionuclides and their impact on the stability and both in vitro and in vivo performances are discussed.

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“…Nanoparticles intrinsically labeled using radionuclides such as 64 Cu, 72 As, 111 In, 153 Sm, 177 Lu and 198 Au, without employing chelators, have also been reported [ 34 , 35 , 36 , 37 ]. 198 Au emits a beta energy (0.96 MeV) ideal to penetrate within the tumor tissue up to 11 mm, providing cross-fire effects which can destroy the tumor cells [ 38 ].…”

Section: Radionuclides For Radiolabeling Various Nanoparticlesmentioning

confidence: 99%

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

et al. 2022

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The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ‘Nanosized delivery systems for radiopharmaceuticals’ involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications—all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.

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Synthesis, chemical and biochemical characterization of Lu2O3-iPSMA nanoparticles activated by neutron irradiation

Cited by 13 publications

References 42 publications

Design, Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging

Design, Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging

Inorganic Radiolabeled Nanomaterials in Cancer Therapy: A Review

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

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