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Authors = Tom Bäck

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18 pages, 3589 KiB  
Article
Pretargeted Alpha Therapy of Disseminated Cancer Combining Click Chemistry and Astatine-211
by Chiara Timperanza, Holger Jensen, Tom Bäck, Sture Lindegren and Emma Aneheim
Pharmaceuticals 2023, 16(4), 595; https://doi.org/10.3390/ph16040595 - 15 Apr 2023
Cited by 12 | Viewed by 3406
Abstract
To enhance targeting efficacy in the radioimmunotherapy of disseminated cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with a modified monoclonal antibody that has an affinity for both tumor antigens and radiolabeled carriers. In this work, we [...] Read more.
To enhance targeting efficacy in the radioimmunotherapy of disseminated cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with a modified monoclonal antibody that has an affinity for both tumor antigens and radiolabeled carriers. In this work, we aimed to synthesize and evaluate poly-L-lysine-based effector molecules for pretargeting applications based on the tetrazine and trans-cyclooctene reaction using 211At for targeted alpha therapy and 125I as a surrogate for the imaging radionuclides 123, 124I. Poly-L-lysine in two sizes was functionalized with a prosthetic group, for the attachment of both radiohalogens, and tetrazine, to allow binding to the trans-cyclooctene-modified pretargeting agent, maintaining the structural integrity of the polymer. Radiolabeling resulted in a radiochemical yield of over 80% for astatinated poly-L-lysines and a range of 66–91% for iodinated poly-L-lysines. High specific astatine activity was achieved without affecting the stability of the radiopharmaceutical or the binding between tetrazine and transcyclooctene. Two sizes of poly-L-lysine were evaluated, which displayed similar blood clearance profiles in a pilot in vivo study. This work is a first step toward creating a pretargeting system optimized for targeted alpha therapy with 211At. Full article
(This article belongs to the Special Issue Targeted Alpha Therapy (TAT): Progress in Radionuclide Production, Radiochemistry and Applications)
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12 pages, 1594 KiB  
Communication
Surface Adsorption of the Alpha-Emitter Astatine-211 to Gold Nanoparticles Is Stable In Vivo and Potentially Useful in Radionuclide Therapy
by Emanuel Sporer, Christian B. M. Poulie, Sture Lindegren, Emma Aneheim, Holger Jensen, Tom Bäck, Paul J. Kempen, Andreas Kjaer, Matthias M. Herth and Andreas I. Jensen
J. Nanotheranostics 2021, 2(4), 196-207; https://doi.org/10.3390/jnt2040012 - 1 Oct 2021
Cited by 8 | Viewed by 4317
Abstract
Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. [...] Read more.
Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT. Full article
(This article belongs to the Special Issue Recent Advancements in Nanoparticle Based Imaging and Therapy)
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15 pages, 1527 KiB  
Article
Stability of Patches of Higher Population Density within the Heterogenous Distribution of the Gray Field Slug Deroceras reticulatum in Arable Fields in the UK
by Emily Forbes, Matthew Back, Andrew Brooks, Natalia B. Petrovskaya, Sergei V. Petrovskii, Tom Pope and Keith F.A. Walters
Insects 2021, 12(1), 9; https://doi.org/10.3390/insects12010009 - 25 Dec 2020
Cited by 5 | Viewed by 2749
Abstract
Exploitation of heterogenous distributions of Deroceras reticulatum, in arable fields by targeting molluscicide applications toward areas with higher slug densities, relies on these patches displaying sufficient spatio-temporal stability. Regular sampling of slug activity/distribution was undertaken using 1 ha rectangular grids of 100 [...] Read more.
Exploitation of heterogenous distributions of Deroceras reticulatum, in arable fields by targeting molluscicide applications toward areas with higher slug densities, relies on these patches displaying sufficient spatio-temporal stability. Regular sampling of slug activity/distribution was undertaken using 1 ha rectangular grids of 100 refuge traps established in 22 commercial arable field crops. Activity varied significantly between the three years of the study, and the degree of aggregation (Taylor’s Power Law) was higher in fields with higher mean trap catches. Hot spot analysis detected statistically significant spatial clusters in all fields, and in 162 of the 167 individual assessment visits. The five assessment visits in which no clusters were detected coincided with low slug activity (≤0.07 per trap). Generalized Linear Models showed significant spatial stability of patches in 11 fields, with non-significant fields also characterized by low slug activity (≤1.2 per trap). Mantel’s permutation tests revealed a high degree of correlation between location of individual patches between sampling dates. It was concluded that patches of higher slug density were spatio-temporally stable, but detection using surface refuge traps (which rely on slug activity on the soil surface) was less reliable when adverse environmental conditions resulted in slugs retreating into the upper soil horizons. Full article
(This article belongs to the Special Issue Biology and Management of Slug and Snail Pests)
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