scholarly journals Tailoring the Radionuclide Encapsulation and Surface Chemistry of La(223Ra)VO4 Nanoparticles for Targeted Alpha Therapy

2021 ◽  
Vol 2 (1) ◽  
pp. 33-50
Author(s):  
Miguel Toro-González ◽  
Allison Peacock ◽  
Andrew Miskowiec ◽  
David A. Cullen ◽  
Roy Copping ◽  
...  
Keyword(s):  
Surface Chemistry ◽  
Radiochemical Yield ◽  
Hydrodynamic Diameter ◽  
Targeted Alpha Therapy ◽  
Innovative Solutions ◽  
High Fraction ◽  
Phosphate Buffered Saline ◽  
Influence Of Ph ◽  
Alpha Therapy ◽  
Target Effects

The development of targeted alpha therapy (TAT) as a viable cancer treatment requires innovative solutions to challenges associated with radionuclide retention to enhance local tumor cytotoxicity and to minimize off-target effects. Nanoparticles (NPs) with high encapsulation and high retention of radionuclides have shown potential in overcoming these issues. This article shows the influence of pH on the structure of lanthanum vanadate (LaVO4) NPs and its impact on the radiochemical yield of 223Ra and subsequent retention of its decay daughters, 211Pb and 211Bi. An acidic pH (4.9) results in a high fraction of La(223Ra)VO4 NPs with tetragonal structure (44.6–66.1%) and a 223Ra radiochemical yield <40%. Adjusting the pH to 11 yields >80% of La(223Ra)VO4 NPs with monoclinic structure and increases the 223Ra radiochemical yield >85%. The leakage of decay daughters from La(223Ra)VO4 NPs (pH 11) was <5% and <0.5% when exposed to deionized water and phosphate-buffered saline, respectively. Altering the surface chemistry of La(223Ra)VO4 NPs with carboxylate and phosphate compounds resulted in a threefold decrease in hydrodynamic diameter and a 223Ra radiochemical yield between 74.7% and 99.6%. These results show the importance of tailoring the synthesis parameters and surface chemistry of LaVO4 NPs to obtain high encapsulation and retention of radionuclides.

Nanoconstructs in Targeted Alpha-Therapy

2015 ◽  
Vol 4 (2) ◽  
pp. 71-76 ◽  
Author(s):  
Jan Kozempel ◽  
Martin Vlk
Keyword(s):  
Targeted Alpha Therapy ◽  
Alpha Therapy

scholarly journals Manual on the proper use of sodium astatide ([211At]NaAt) injections in clinical trials for targeted alpha therapy (1st edition)

2021 ◽  
Author(s):  
Tadashi Watabe ◽  
Makoto Hosono ◽  
Seigo Kinuya ◽  
Takahiro Yamada ◽  
Sachiko Yanagida ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Japanese Society ◽  
Radiation Safety ◽  
Safety Management ◽  
Evaluation Methodology ◽  
Targeted Alpha Therapy ◽  
Safety Issues ◽  
Safety Standards ◽  
And Training ◽  
Alpha Therapy

AbstractWe present the guideline for use of [211At] sodium astatide (NaAt) for targeted alpha therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on 8th Feb, 2021. The study showed that patients receiving [211At]NaAt do not need to be admitted to a radiotherapy room and outpatient treatment is possible. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers. Precautions for patients and their families, safety management associated with the use of [211At]NaAt, education and training, and disposal of medical radioactive contaminants are also included in this guideline. Treatment using [211At]NaAt in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection and evaluation methodology shown here are considered internationally useful as well.

scholarly journals Evaluation of Actinium-225 radiolabeled cyclized alpha-melanocyte stimulating hormone (CycMSH) peptide for targeted alpha therapy

2021 ◽  
Vol 96-97 ◽  
pp. S101
Author(s):  
Victoria Brown ◽  
Cristina Rodríguez-Rodríguez ◽  
Chengcheng Zhang ◽  
Keiran Maskell ◽  
Francois Benard ◽  
...  
Keyword(s):  
Targeted Alpha Therapy ◽  
Melanocyte Stimulating Hormone ◽  
Alpha Therapy ◽  
Stimulating Hormone

scholarly journals Extended single-dose toxicity study of [211At]NaAt in mice for the first-in-human clinical trial of targeted alpha therapy for differentiated thyroid cancer

2021 ◽  
Author(s):  
Tadashi Watabe ◽  
Kazuko Kaneda-Nakashima ◽  
Kazuhiro Ooe ◽  
Yuwei Liu ◽  
Kenta Kurimoto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Thyroid Cancer ◽  
Single Dose ◽  
General Condition ◽  
Blood Test ◽  
Differentiated Thyroid Cancer ◽  
Targeted Alpha Therapy ◽  
Evaluation Point ◽  
Alpha Therapy

Abstract Objective Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [211At]NaAt to determine the FIH dose. Methods [211At]NaAt solution was injected into normal 6-week-old mice (male (n = 50) and female (n = 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (n = 20), 20 MBq/kg (n = 20), 50 MBq/kg (n = 30), saline control (n = 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity: n = 80) or 14 days (n = 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups. Results No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of [211At]NaAt. Conclusions In the extended single-dose toxicity study of [211At]NaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.

scholarly journals Gold nanoparticle bioconjugates labelled with 211At for targeted alpha therapy

RSC Advances ◽  
2017 ◽  
Vol 7 (65) ◽  
pp. 41024-41032 ◽  
Author(s):  
L. Dziawer ◽  
P. Koźmiński ◽  
S. Męczyńska-Wielgosz ◽  
M. Pruszyński ◽  
M. Łyczko ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Gold Nanoparticle ◽  
Radionuclide Therapy ◽  
Targeted Alpha Therapy ◽  
Alpha Therapy

Gold nanoparticles labeled with 211At are very effective in radionuclide therapy.

scholarly journals Combining Bismuth-213 with Nanobodies: Finding the Perfect Match for Targeted Alpha Therapy

2019 ◽  
Vol 50 (1) ◽  
pp. S7-S8
Author(s):  
Yana Dekempeneer ◽  
Vicky Caveliers ◽  
Matthias D’huyvetter ◽  
Dominic Maertens ◽  
Mireille Gysemans ◽  
...  
Keyword(s):  
Perfect Match ◽  
Targeted Alpha Therapy ◽  
Alpha Therapy

scholarly journals Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

2020 ◽  
Author(s):  
Richard Edwards ◽  
Hannah Greenwood ◽  
Timothy Witney
Keyword(s):  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Reaction Conditions ◽  
Positron Emission ◽  
Optimized Protocol ◽  
Cancer Types ◽  
Automated Procedures ◽  
Phosphate Buffered Saline ◽  
High Radioactivity

<p><i>Purpose</i>: (S)-4-(3-<sup>18</sup>F-Fluoropropyl)-ʟ-Glutamic Acid ([<sup>18</sup>F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x<sub>C</sub><sup>-</sup>, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [<sup>18</sup>F]FSPG production are required. Here, we report a cassette-based method to produce [<sup>18</sup>F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [<sup>18</sup>F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [<sup>18</sup>F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [<sup>18</sup>F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [<sup>18</sup>F]FSPG in phosphate-buffered saline. Subsequently, the [<sup>18</sup>F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.</p><p><i>Results</i>: The optimized protocol produced [<sup>18</sup>F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [<sup>18</sup>F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [<sup>18</sup>F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [<sup>18</sup>F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.</p>

scholarly journals Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

2020 ◽  
Author(s):  
Richard Edwards ◽  
Hannah Greenwood ◽  
Timothy Witney
Keyword(s):  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Reaction Conditions ◽  
Positron Emission ◽  
Optimized Protocol ◽  
Cancer Types ◽  
Automated Procedures ◽  
Phosphate Buffered Saline ◽  
High Radioactivity

<p><i>Purpose</i>: (S)-4-(3-<sup>18</sup>F-Fluoropropyl)-ʟ-Glutamic Acid ([<sup>18</sup>F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x<sub>C</sub><sup>-</sup>, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [<sup>18</sup>F]FSPG production are required. Here, we report a cassette-based method to produce [<sup>18</sup>F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [<sup>18</sup>F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [<sup>18</sup>F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [<sup>18</sup>F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [<sup>18</sup>F]FSPG in phosphate-buffered saline. Subsequently, the [<sup>18</sup>F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.</p><p><i>Results</i>: The optimized protocol produced [<sup>18</sup>F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [<sup>18</sup>F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [<sup>18</sup>F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [<sup>18</sup>F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.</p>

Sign in / Sign up

Export Citation Format

Share Document