Neutron-activated theranostic radionuclides for nuclear medicine

Tan, Hun Yee; Yeong, Chai Hong; Wong, Yin How; McKenzie, Molly; Kasbollah, Azahari; Shah, Mohammad Nazri Md; Perkins, Alan C.

doi:10.1016/j.nucmedbio.2020.09.005

Cited by 27 publications

(26 citation statements)

References 126 publications

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“…The labelling chemistry of 177 Lu is well established and permits stable labelling of targeting proteins and peptides [11]. Those properties make 177 Lu one of the most clinically used radionuclides in targeted radionuclide therapy [1,[12][13][14]. However, this nuclide has residualizing properties, which means that its retention time in kidneys would be long.…”

Section: Introductionmentioning

confidence: 99%

Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody® Molecules 177Lu-ABY-271 and 177Lu-ABY-027: Impact of DOTA Position on ABD Domain

Liu

Vorobyeva

et al. 2021

Pharmaceutics

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Radiolabeled Affibody-based targeting agent 177Lu-ABY-027, a fusion of an anti-HER2 Affibody molecule with albumin binding domain (ABD) site-specifically labeled at the C-terminus, has demonstrated a promising biodistribution profile in mice; binding of the construct to albumin prevents glomerular filtration and significantly reduces renal uptake. In this study, we tested the hypothesis that site-specific positioning of the chelator at helix 1 of ABD, at a maximum distance from the albumin binding site, would further increase the strength of binding to albumin and decrease the renal uptake. The new construct, ABY-271 with DOTA conjugated at the back of ABD, has been labelled with 177Lu. Targeting properties of 177Lu-ABY-271 and 177Lu-ABY-027 were compared directly. 177Lu-ABY-271 specifically accumulated in SKOV-3 xenografts in mice. The tumor uptake of 177Lu-ABY-271 exceeded uptake in any other organ 24 h and later after injection. However, the renal uptake of 177Lu-ABY-271 was two-fold higher than the uptake of 177Lu-ABY-027. Thus, the placement of chelator on helix 1 of ABD does not provide desirable reduction of renal uptake. To conclude, minimal modification of the design of Affibody molecules has a strong effect on biodistribution, which cannot be predicted a priori. This necessitates extensive structure-properties relationship studies to find an optimal design of Affibody-based targeting agents for therapy.

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Section: Introductionmentioning

confidence: 99%

Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody® Molecules 177Lu-ABY-271 and 177Lu-ABY-027: Impact of DOTA Position on ABD Domain

Liu

Vorobyeva

et al. 2021

Pharmaceutics

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“…Radioactive isotopes utilized for diagnostic and therapeutic purposes in medical institutions decay naturally and emit radiation. The types of radiation emitted include α-rays, β-rays, gamma rays, and X-rays, and the administered radioisotope cannot be controlled like an X-ray generator because it has its characteristics [36,37]. The emitted radiation generally has high energy and penetrating power, and since the direction of emission is not determined, radiation workers and people around the patient face a high risk of exposure.…”

Section: Discussionmentioning

confidence: 99%

Tungsten-Based Hybrid Composite Shield for Medical Radioisotope Defense

Kim

2022

Materials

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The shielding performance of shielding clothing is typically improved by increasing the shielding material content, but this lowers the tensile strength of the material. The weight and wearability of the shielding suit are also adversely affected. Important considerations when developing shielding fabric are thickness and flexibility to allow the wearer sufficient mobility. Insufficient thickness lowers the shielding performance, whereas excessive thickness decreases the flexibility of the garment. This study aimed to develop a composite shield that reproduces the shielding performance and meets the flexibility of the process technology. The new shield was manufactured by combining two layers: the shielding fabric fabricated from tungsten wire and a shielding sheet produced by mixing a polymer (PDMS) with tungsten powder. These two shields were bonded to develop a double hybrid composite. Compared with the existing shielding sheet (produced from lead equivalent of 0.55 mmPb), the shielding performance of the hybrid composite shield improved by approximately 17% on average and the tensile strength was 53% higher. The hybrid composite shield has a thickness of 1.35 ± 0.02 mm and delivers the same shielding performance as the lead equivalent. The new hybrid composite shield offers higher wearer mobility while shielding against radiation exposure in medical institutions.

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“…A wide array of therapeutic applications have been investigated with pre-clinical and clinical trials and studies being reported for radiopharmaceutical therapies for bone marrow cancer (Bayouth et al 1995a , b ; Giralt et al 2003 ; Christoforidou et al 2017 ), metastatic bone pain palliation (Voorde et al 2019 ; Bahrami-Samani et al 2010 ), brain cancer (Huh et al 2005 ; Ha et al 2013 ), liver cancer (Cho et al 2005 ; Kim et al 2006 ), and prostate cancer (Seong et al 2005 ; Kwak et al 2005 ), among others. This radionuclide has gained attention for its potential theranostic applications due to its favourable decay characteristics that allow for its use as both a therapeutic agent and an imaging agent (Tan et al 2020 ). 166 Ho has a physical half-life of 26.8 h and emits β − -particles [E βmax = 1.854 MeV (50.0%) and 1.774 MeV (48.7%)] suitable for β − -therapy (Voorde et al 2019 ), while also producing γ-emissions (80.6 keV, 6.2%) that can be used for γ-scintigraphy or SPECT without an excessive dose burden to the patient or radiation damage during transportation, handling, storage or administration since the γ-emissions are not high-energy.…”

Section: Holmium: 166 Homentioning

confidence: 99%

“…166 Ho has a physical half-life of 26.8 h and emits β − -particles [E βmax = 1.854 MeV (50.0%) and 1.774 MeV (48.7%)] suitable for β − -therapy (Voorde et al 2019 ), while also producing γ-emissions (80.6 keV, 6.2%) that can be used for γ-scintigraphy or SPECT without an excessive dose burden to the patient or radiation damage during transportation, handling, storage or administration since the γ-emissions are not high-energy. In addition, the highly paramagnetic nature of 166 Ho (4 f 11 with 3 unpaired electrons) has led to its use as a magnetic resonance imaging (MRI) contrast agent (Shi et al 2017 ; Tan et al 2020 ; Vente et al 2007 ). These properties allow for the unification of both aspects of the theranostic concept in one radionuclide, which has advanced 166 Ho as a promising option over the more readily-researched theranostically-matched radionuclide pair approach, due to the alleviation of the need for investigation into theranostic counterparts that satisfy the requirements of similar chemical properties, production availability, chelation kinetics, biodistribution, pharmacokinetics and toxicity concerns, among others.…”

Section: Holmium: 166 Homentioning

confidence: 99%

Cutting edge rare earth radiometals: prospects for cancer theranostics

Sadler

Hogan

Fraser

et al. 2022

EJNMMI radiopharm. chem.

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Background With recent advances in novel approaches to cancer therapy and imaging, the application of theranostic techniques in personalised medicine has emerged as a very promising avenue of research inquiry in recent years. Interest has been directed towards the theranostic potential of Rare Earth radiometals due to their closely related chemical properties which allow for their facile and interchangeable incorporation into identical bifunctional chelators or targeting biomolecules for use in a diverse range of cancer imaging and therapeutic applications without additional modification, i.e. a “one-size-fits-all” approach. This review will focus on recent progress and innovations in the area of Rare Earth radionuclides for theranostic applications by providing a detailed snapshot of their current state of production by means of nuclear reactions, subsequent promising theranostic capabilities in the clinic, as well as a discussion of factors that have impacted upon their progress through the theranostic drug development pipeline. Main body In light of this interest, a great deal of research has also been focussed towards certain under-utilised Rare Earth radionuclides with diverse and favourable decay characteristics which span the broad spectrum of most cancer imaging and therapeutic applications, with potential nuclides suitable for α-therapy (149Tb), β−-therapy (47Sc, 161Tb, 166Ho, 153Sm, 169Er, 149Pm, 143Pr, 170Tm), Auger electron (AE) therapy (161Tb, 135La, 165Er), positron emission tomography (43Sc, 44Sc, 149Tb, 152Tb, 132La, 133La), and single photon emission computed tomography (47Sc, 155Tb, 152Tb, 161Tb, 166Ho, 153Sm, 149Pm, 170Tm). For a number of the aforementioned radionuclides, their progression from ‘bench to bedside’ has been hamstrung by lack of availability due to production and purification methods requiring further optimisation. Conclusions In order to exploit the potential of these radionuclides, reliable and economical production and purification methods that provide the desired radionuclides in high yield and purity are required. With more reactors around the world being decommissioned in future, solutions to radionuclide production issues will likely be found in a greater focus on linear accelerator and cyclotron infrastructure and production methods, as well as mass separation methods. Recent progress towards the optimisation of these and other radionuclide production and purification methods has increased the feasibility of utilising Rare Earth radiometals in both preclinical and clinical settings, thereby placing them at the forefront of radiometals research for cancer theranostics.

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Neutron-activated theranostic radionuclides for nuclear medicine

Cited by 27 publications

References 126 publications

Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody® Molecules 177Lu-ABY-271 and 177Lu-ABY-027: Impact of DOTA Position on ABD Domain

Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody® Molecules 177Lu-ABY-271 and 177Lu-ABY-027: Impact of DOTA Position on ABD Domain

Tungsten-Based Hybrid Composite Shield for Medical Radioisotope Defense

Cutting edge rare earth radiometals: prospects for cancer theranostics

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