A Multifunctional Radiotheranostic Agent for Dual Targeting of Breast Cancer Cells

Vultos, Filipe; Fernandes, Célia; Mendes, Filipa; Marques, Fernanda; Correia, João D. G.; Santos, Isabel Cristina Ramos Vieira; Gano, Lurdes

doi:10.1002/cmdc.201700287

Cited by 13 publications

(10 citation statements)

References 30 publications

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“…An early experiment was conducted by DeSombre et al (1992) , who showed that 123 I-labeled estrogen analogs result in a significant reduction in clonogenic survival of ER expressing cells. DeSombre and others subsequently evaluated various radiolabeled agents for the treatment of cancer, including 123 I- and 111 In-labeled analogs of estrogen and diethylstilboestrol, a non-steroid ER agonist ( DeSombre et al, 2000 ; Yasui et al, 2001 ; Fischer et al, 2008 ; Vultos et al, 2017 ). Kortylewicz et al (2012) developed an interesting hybrid molecule that exploits dual AR targeting and S-phase specific cell kill by linking 5α-dihydrotestosterone with 5-radioiodo-2′-deoxyuridine.…”

Section: Subcellular Targets For Radionuclide Therapymentioning

confidence: 99%

Subcellular Targeting of Theranostic Radionuclides

et al. 2018

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The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging rely on a radiolabeled vector to specifically target cancer cells. Radionuclides that emit β particles have thus far dominated the field of targeted radionuclide therapy (TRT), mainly because the longer range (μm–mm track length) of these particles offsets the heterogeneous expression of the molecular target. Shorter range (nm–μm track length) α- and Auger electron (AE)-emitting radionuclides on the other hand provide high ionization densities at the site of decay which could overcome much of the toxicity associated with β-emitters. Given that there is a growing body of evidence that other sensitive sites besides the DNA, such as the cell membrane and mitochondria, could be critical targets in TRT, improved techniques in detecting the subcellular distribution of these radionuclides are necessary, especially since many β-emitting radionuclides also emit AE. The successful development of TRT agents capable of homing to targets with subcellular precision demands the parallel development of quantitative assays for evaluation of spatial distribution of radionuclides in the nm–μm range. In this review, the status of research directed at subcellular targeting of radionuclide theranostics and the methods for imaging and quantification of radionuclide localization at the nanoscale are described.

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Section: Subcellular Targets For Radionuclide Therapymentioning

confidence: 99%

Subcellular Targeting of Theranostic Radionuclides

et al. 2018

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“…Compound 1, ethyl 4-((2-(tert-butoxycarbonylamino)ethyl) (2-(4-(2-(2,5-dioxopyrrolidinyloxy)-2-oxoethyl)-3,5-dimethylpyrazol)ethyl)amino) butanoate, was prepared as described in the literature [63]. Compound 2, 3,6-bis(dimethylamino)-10-(3-(1,3-dioxoisoindolin-2-yl)-propyl)acridinium iodide (2), was prepared according to the published methods [64]. The starting material fac-[Re(H 2 O) 3 (CO) 3 ]Br was synthesized according to the literature [65].…”

Section: Methodsmentioning

confidence: 99%

Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus

Fernandes

Palma

Silva

et al. 2022

IJMS

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Although 99mTc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available “model” radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates 99mTc-TPP-BBN and 99mTc-AO-BBN (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. 99mTc-TPP-BBN and 99mTc-AO-BBN caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener 99mTc-BBN, leading to an augmented formation of γH2AX foci and micronuclei. 99mTc-TPP-BBN also caused a reduction of the mtDNA copy number, although it enhanced the ATP production by PC3 cells. These differences can be attributed to the augmented uptake of 99mTc-TPP-BBN in the mitochondria and enhanced uptake of 99mTc-AO-BBN in the nucleus, allowing the irradiation of these radiosensitive organelles with the short path-length AEs emitted by 99mTc. In particular, the results obtained for 99mTc-TPP-BBN reinforce the relevance of targeting the mitochondria to promote stronger radiobiological effects by AE-emitting radioconjugates.

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“…By contrast, unlike G4-binders, several research groups have studied radiolabeled classical DNA intercalators aiming to deliver Auger electrons to short (sub)nanomolar distances to DNA and induce lethal DNA damage [76,[165][166][167][168][169][170][171]. In particular, these studies included complexes with Auger-electron emitting radiometals, such as 99m Tc and 111 In.…”

Section: Dna-targeted Radiocomplexesmentioning

confidence: 99%

Metal-Based G-Quadruplex Binders for Cancer Theranostics

et al. 2021

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The ability of fluorescent small molecules, such as metal complexes, to selectively recognize G-quadruplex (G4) structures has opened a route to develop new probes for the visualization of these DNA structures in cells. The main goal of this review is to update the most recent research efforts towards the development of novel cancer theranostic agents using this type of metal-based probes that specifically recognize G4 structures. This encompassed a comprehensive overview of the most significant progress in the field, namely based on complexes with Cu, Pt, and Ru that are among the most studied metals to obtain this class of molecules. It is also discussed the potential interest of obtaining G4-binders with medical radiometals (e.g., 99mTc, 111In, 64Cu, 195mPt) suitable for diagnostic and/or therapeutic applications within nuclear medicine modalities, in order to enable their theranostic potential.

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A Multifunctional Radiotheranostic Agent for Dual Targeting of Breast Cancer Cells

Cited by 13 publications

References 30 publications

Subcellular Targeting of Theranostic Radionuclides

Subcellular Targeting of Theranostic Radionuclides

Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus

Metal-Based G-Quadruplex Binders for Cancer Theranostics

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