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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Actinium Pharmaceuticals Inc is presently developing tumor-targeted antibodies conjugated to the alpha-emitting radioisotopes Actinium-225 and Bismuth-213. The company claims that the use of alpha particles (a treatment they call Alpha Particle Immunotherapy or “APIT”) has advantages over beta particles because the killing power of radioactivity is directly proportional to its energy but inversely proportional to its range. Thus, alpha particles carry the most energy (i.e., 100 times more than beta particles) but travel the shortest path. This contrasts with beta particles which are less energetic but travel further in the body causing more collateral damage to healthy tissue. Another potential advantage is that both Actinium-225 and the isotope derived from it, Bismuth-213, have relatively short half-lives (10 days and 46 minutes, respectively) and favorable pharmacokinetics. However, for logistical and cost reasons the company is focusing on antibodies conjugated to Actinium-225.
Radioimmunotherapy of Hematological Malignancies
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
α-Emitters produce a helium nucleus particle of very high energy but with a very short path length. The high linear energy transfer (LET) radiation of α-emitters may be lethal to cells with a single collision; however, the very short path length means that the isotope must be adjacent to, or internalized by, the cell to be effective and is likely to have little or no cross-fire effect. The suitability of α-emitters, therefore, appears limited to readily accessible tumors such as leukemia cells confined to the blood or bone marrow. The short half-life of a-emitters [e.g., astatine-211 (211At)—7 hours or bismuth-213 (213Bi)—45 minutes] complicates the radiopharmaceutical preparation, meaning that such radioisotopes are likely to require generation on the same site as delivery in the clinic. Despite this logistical hurdle, early clinical data in the treatment of leukemia appear extremely promising (19,20).
Indoor Air Quality
Published in James M. Rippe, Lifestyle Medicine, 2019
Anthony C. Campagna, Dhruv Desai
Radon-222 is a noble gas that is produced from the decay of uranium-238 and radium-226, which are naturally present in the earth’s rock and soil. It decays with a half-life of 3.8 days. It can diffuse itself into the soil and air before decaying. The breakdown of radon-222 occurs by emission of an alpha particle which produces radioactive progeny that include polonium-218 and polonium-214.34,35 These are known as the “short-lived” progeny, and they, in turn, break down into “long-lived” progeny that include lead-210, which yields bismuth-210, which yields the stable isotopes polonium-210 and lead-206. This whole decay process takes hundreds of years. When inhaled into the lung, the alpha-particles can damage cellular DNA and lead to mutagenesis in never-smoking lung cancer cases.36
Clinical development of an anti-GPC-1 antibody for the treatment of cancer
Published in Expert Opinion on Biological Therapy, 2022
Saikat Ghosh, Pie Huda, Nicholas Fletcher, Douglas Campbell, Kristofer J. Thurecht, Bradley Walsh
Recently, Sabanathan et al. highlighted the importance of GPC-1 as a radioimmunotherapy target in an extensive review [50]. A list of preclinical and clinical studies conducted using GPC-1 directed radiopharmaceuticals were compiled in that article. A comprehensive literature survey suggested that the majority of the RIT trials reported to date involved the GPC-1 antibody, Miltuximab® (Glytherix Ltd.) [41,51,52] or its parent antibody BLCA-3822, [34]. Since its early days as BLCA-38, to the present-day Miltuximab®, this anti-GPC-1 antibody has been extensively evaluated for its potential as an RIT agent. Initial imaging studies using iodine-131 (131I) and samarium-153 (153Sm)-conjugated BLCA-38 were successful in visualizing human bladder cancer xenografts [53,54]. On the other hand, iodine-125 (125I) and bismuth-213 (213Bi) coupled BLCA-38 inhibited growth of human prostate cancer xenografts in mouse models [40,55]. In the most recent preclinical study, 89Zr-labeled Miltuximab® and 177Lu-labeled Miltuximab® were tested for their tumor imaging and therapeutic capabilities, respectively, in a DU-145 prostate cancer model [51]. 89Zr-Miltuximab® emerged as a promising PET tracer for imaging DU-145 tumors and the β-emitting 177Lu-Miltuximab® was highly effective in inhibiting tumor growth in vivo. 177Lu-Miltuximab® enabled dose-dependent (3, 6, and 10 MBq) regression of prostatic tumors significantly, with a substantial improvement in ethical endpoint survival as compared to controls.
The potential of PSMA-targeted alpha therapy in the management of prostate cancer
Published in Expert Review of Anticancer Therapy, 2020
Luca Filippi, Agostino Chiaravalloti, Orazio Schillaci, Oreste Bagni
Beside 223Ra-radionuclide, actinium-225 (225Ac) and bismuth-213 (213Bi) represent the 2 alpha emitters with the most promising characteristics for TAT. 225Ac has a half-life of 9.9 days and presents a complex pathway of disintegration leading to the nuclide thallium-209 (209Tl). In 225Ac disintegration cascade 4 alpha-emitting daughters with an energy ranging from 5.8 to 8.4 MeV and a tissue penetration between 47 and 85 micron are produced. If on the one hand, the long half-life and the complex mechanism of disintegration make 225Ac a potentially powerful tumoricidal weapon, on the other hand the numerous recoiling daughters make this radionuclide less controllable as a TAT agent. Figure 3 schematizes 225Ac complex pathway of disintegration.
Peptide receptor radionuclide therapy in neuroendocrine neoplasms and related tumors: from fundamentals to personalization and the newer experimental approaches
Published in Expert Review of Precision Medicine and Drug Development, 2023
6. Bismuth-213 (213Bi): 213Bi is an α emitter (T1/2 = 45.6 min, Eα = 8.4 MeV, γ = 440 keV, α-particle range = 40–80 µm) and decay product of 225Ac. It also emits β− particles (492 keV in 98% abundance). Just like 225Ac, this has also shown proven efficacy even in 177Lu/90Y resistant patients [12]. It forms a stable chelate complex with DTPA, NETA, and DOTA and has more stable chemistry for therapeutic uses [11]. It has the benefit of manufacturing and suitable scheduling patients in clinical seating as it can be extracted from 225Ac in form of the 225Ac-131Bi generator system.