Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for alpha radionuclide therapy

Ogawa, Kenji; Mizuno, Yoshiaki; Washiyama, Kohshin; Shiba, Kazuhiro; Takahashi, N.; Kozaka, Takashi; Watanabe, Shigeki; Shinohara, Atsushi; Odani, Akira

doi:10.1016/j.nucmedbio.2015.07.001

Cited by 23 publications

(17 citation statements)

References 17 publications

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“…In this study, to minimize both the number of mice consumed in the experiment and the potential for experimental errors, we co-injected radiobrominated and radioiodinated compounds into mice 30 , 31 . The biodistribution of [ 77 Br] 2 and [ 125 I] 4 in ddY mice were summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Radiotracer uptake experiments in tumor cells were performed using BxPC3-luc and MCF7 cell lines. To compare the uptake between radiobrominated compounds, [ 77 Br] 2 and [ 77 Br] 3 , and the corresponding radioiodinated compounds, [ 125 I] 4 and [ 125 I] 5 , the cellular uptake experiments were performed by a double tracer method as described previously with a slight modification 30 , 31 , 35 . Briefly, the cells were seeded in RPMI 1640 medium containing 10% FBS and antibiotics on six-well plates (2 × 10 5 cells/well) for 24 h in a 5% CO 2 incubator at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

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Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes

Effendi

Mishiro

Takarada

et al. 2018

Sci Rep

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Platelet-derived growth factor receptor beta (PDGFRβ) affects in numerous human cancers and has been recognized as a promising molecular target for cancer therapies. The overexpression of PDGFRβ could be a biomarker for cancer diagnosis. Radiolabeled ligands having high affinity for the molecular target could be useful tools for the imaging of overexpressed receptors in tumors. In this study, we aimed to develop radiobrominated PDGFRβ ligands and evaluate their effectiveness as PDGFRβ imaging probes. The radiolabeled ligands were designed by modification of 1-{2-[5-(2-methoxyethoxy)-1H- benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine (1), which shows selective inhibition profile toward PDGFRβ. The bromine atom was introduced directly into C-5 of the quinoline group of 1, or indirectly by the conjugation of 1 with the 3-bromo benzoyl group. [77Br]1-{5-Bromo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([77Br]2) and [77Br]-N-3-bromobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([77Br]3) were prepared using a bromodestannylation reaction. In a cellular uptake study, [77Br]2 and [77Br]3 more highly accumulatd in BxPC3-luc cells (PDGFRβ-positive) than in MCF7 cells (PDGFRβ-negative), and their accumulation was significantly reduced by pretreatment with inhibitors. In biodistribution experiments, [77Br]2 accumulation was higher than [77Br]3 accumulation at 1 h postinjection. These findings suggest that [76Br]2 is more promising for positron emission tomography (PET) imaging of PDGFRβ than [76Br]3.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes

Effendi

Mishiro

Takarada

et al. 2018

Sci Rep

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“…58,61 Despite the stability issue, relative stability of a few 211 At compounds, proteins, or small molecules labeled by aromatic intermediates have been observed and may be explained by fast kidney clearance in relation to slow or noninternalization properties. [63][64][65]93 In addition, 211 At-labeled antibodies synthesized with existing well-established chemical methods show sufficient stability in intracavitary applications and allow for treatment in several different cavity modalities such as intraperitoneal, intrathecal, and in the blood compartment following, for example, leukemia or lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Realizing Clinical Trials with Astatine-211: The Chemistry Infrastructure

Lindegren

Albertsson

Bäck

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Despite the consensus around the clinical potential of the a-emitting radionuclide astatine-211 (211 At), there are only a limited number of research facilities that work with this nuclide. There are three main reasons for this: (1) Scarce availability of the nuclide. Despite a relatively large number of globally existing cyclotrons capable of producing 211 At, few cyclotron facilities produce the nuclide on a regular basis. (2) Lack of a chemical infrastructure, that is, isolation of 211 At from irradiated targets and the subsequent synthesis of an astatinated product. At present, the research groups that work with 211 At depend on custom systems for recovering 211 At from the irradiated targets. Setting up and implementing such custom units require long lead times to provide a proper working system. (3) The chemistry of 211 At. Compared with radiometals there are no well-established and generally accepted synthesis methods for forming sufficiently stable bonds between 211 At and the tumor-specific vector to allow for systemic applications. Herein we present an overview of the infrastructure of producing 211 At radiopharmaceuticals, from target to radiolabeled product including chemical strategies to overcome hurdles for advancement into clinical trials with 211 At.

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“…Astatine ( 211 At) is receiving increasing attention as an alpha-emitter for targeted radionuclide therapy. [64][65][66] Astatine is a halogen element with similar chemical properties to iodine. Alpha particles emitted from 211 At with a branching ratio of 41.8% (5.98MeV) has higher linear energy transfer as compared to beta particles from 131 I (0.97MeV) and exert a better therapeutic effect by inducing DNA double-strand breaks and free radical formation.…”

Section: Discussionmentioning

confidence: 99%

<p>Improving <sup>131</sup>I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles</p>

Goas¹,

Paquet²,

Paquirissamy³

et al. 2019

IJN

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Background: Human trials combining external radiotherapy (RT) and metallic nanoparticles are currently underway in cancer patients. For internal RT, in which a radioisotope such as radioiodine is systemically administered into patients, there is also a need for enhancing treatment efficacy, decreasing radiation-induced side effects and overcoming radio-resistance. However, if strategies vectorising radioiodine through nanocarriers have been documented, sensitizing the neoplasm through the use of nanotherapeutics easily translatable to the clinic in combination with the standard systemic radioiodine treatment has not been assessed yet. Method and materials: The present study explored the potential of hybrid poly (methacrylic acid)-grafted gold nanoparticles to improve the performances of systemic 131 I-mediated RT on cancer cells and in tumor-bearing mice. Such nanoparticles were chosen based on their ability previously described by our group to safely withstand irradiation doses while exhibiting good biocompatibility and enhanced cellular uptake. Results: In vitro clonogenic assays performed on melanoma and colorectal cancer cells showed that poly(methacrylic acid)-grafted gold nanoparticles (PMAA-AuNPs) could efficiently lead to a marked tumor cell mortality when combined to a low activity of radioiodine, which alone appeared to be essentially ineffective on tumor cells. In vivo, tumor enrichment with PMAA-AuNPs significantly enhanced the killing potential of a systemic radioiodine treatment. Conclusion: This is the first report of a simple and reliable nanomedicine-based approach to reduce the dose of radioiodine required to reach curability. In addition, these results open up novel perspectives for using high-Z metallic NPs in additional molecular radiation therapy demonstrating heterogeneous dose distributions.

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Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for alpha radionuclide therapy

Cited by 23 publications

References 17 publications

Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes

Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes

Realizing Clinical Trials with Astatine-211: The Chemistry Infrastructure

<p>Improving <sup>131</sup>I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles</p>

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