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• W2046093911 abstract "Nanoscale materials have been envisioned as carriers for various therapeutic drugs, including radioisotopes. Inorganic nanoparticles (NPs) are particularly appealing vehicles for targeted radiotherapy because they can package several radioactive atoms into a single carrier and can potentially retain daughter radioisotopes produced by in vivo generators such as actinium-225 (225Ac, t1/2 = 10 d). Decay of this radioisotope to stable bismuth-209 proceeds through a chain of short-lived daughters accompanied by the emission of four α-particles that release >27 MeV of energy. The challenge in realizing the enhanced cytotoxic potential of in vivo generators lies in retaining the daughter nuclei at the therapy site. When 225Ac is attached to targeting agents via standard chelate conjugation methods, all of the daughter radionuclides are released after the initial α-decay occurs. In this work, 225Ac was incorporated into lanthanum phosphate NPs to determine whether the radioisotope and its daughters would be retained within the dense mineral lattice. Further, the 225Ac-doped NPs were conjugated to the monoclonal antibody mAb 201B, which targets mouse lung endothelium through the vasculature, to ascertain the targeting efficacy and in vivo retention of radioisotopes. Standard biodistribution techniques and microSPECT/CT imaging of 225Ac as well as the daughter radioisotopes showed that the NPs accumulated rapidly in mouse lung after intravenous injection. By showing that excess, competing, uncoupled antibodies or NPs coupled to control mAbs are deposited primarily in the liver and spleen, specific targeting of NP-mAb 201B conjugates was demonstrated. Biodistribution analysis showed that ∼30% of the total injected dose of La(225Ac)PO4 NPs accumulated in mouse lungs 1 h postinjection, yielding a value of % ID/g >200. Furthermore, after 24 h, 80% of the 213Bi daughter produced from 225Ac decay was retained within the target organ and 213Bi retention increased to ∼87% at 120 h. In vitro analyses, conducted over a 1 month interval, demonstrated that ∼50% of the daughters were retained within the La(225Ac)PO4 NPs at any point over that time frame. Although most of the γ-rays from radionuclides in the 225Ac decay chain are too energetic to be captured efficiently by SPECT detectors, appropriate energy windows were found that provided dramatic microSPECT images of the NP distribution in vivo. We conclude that La(225Ac)PO4−mAb 201B conjugates can be targeted efficiently to mouse lung while partially retaining daughter products and that targeting can be monitored by biodistribution techniques and microSPECT imaging." @default.
• W2046093911 created "2016-06-24" @default.
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• W2046093911 date "2011-03-24" @default.
• W2046093911 modified "2023-10-03" @default.
• W2046093911 title "LaPO₄ Nanoparticles Doped with Actinium-225 that Partially Sequester Daughter Radionuclides" @default.
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• W2046093911 doi "https://doi.org/10.1021/bc100574f" @default.
• W2046093911 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21434681" @default.
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