No abstract

Actinium-225 is a promising isotope for targeted-α therapy. Unfortunately, progress in developing chelators for medicinal applications has been hindered by a limited understanding of actinium chemistry. This knowledge gap is primarily associated with handling actinium, as it is highly radioactive and in short supply. Hence, AcIII reactivity is often inferred from the lanthanides and minor actinides (that is, Am, Cm), with limited success. Here we overcome these challenges and characterize actinium in HCl solutions using X-ray absorption spectroscopy and molecular dynamics density functional theory. The Ac–Cl and Ac–OH2O distances are measured to be 2.95(3) and 2.59(3) Å, respectively. The X-ray absorption spectroscopy comparisons between AcIII and AmIII in HCl solutions indicate AcIII coordinates more inner-sphere Cl1– ligands (3.2±1.1) than AmIII (0.8±0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique AcIII chemical behaviour.

Molecular structures of both Fe"'(TFPPBr8)Cl and Fe"(TFPPBrE)(py)z porphyrins reveal saddle distortions: Fell'-(TFPPBr8)Cl in triclinic space group Pi, a = 13.649(4) A, b = 14.474(4) A, c = 14.537 A, a = 89.26(2)", p = 67.13(1)", y = 71.82(2)", V = 2494.3(13) A3, Z = 2; Fe"(TFPPBrs)(py)z in triclinic space group Pi, a = 12.459-(7) A, b = 13.125(8) A, c = 20.989(11) A, a = 84.72(5)", , L3 = 72.87(4)", y = 69.04(5)", V = 3063(3) A3, Z =2. Similar to other chloro-iron(II1) porphyrins, peff at room temperature (5.96 p~) is that of a 6A1 state; peff at 2 K (4.2 p~) indicates a large zero-field splitting.

Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting. Numerous studies have demonstrated the in vitro and in vivo efficacy of the targeted α-therapy. Radium-223 (Ra) dichloride (Xofigo®) is the first α-emitter to have received FDA approval for the treatment of prostate cancer with metastatic bone lesions. There is a significant increase in the number of clinical trials in oncology using several radionuclides such as Actinium-225 (Ac), Bismuth-213 (Bi), Lead-212 (Pb), Astatine (At) or Radium-223 (Ra) assessing their safety and preliminary activity. This review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.

Cross sections for (223,)(225)Ra, (225)Ac and (227)Th production by the proton bombardment of natural thorium targets were measured at proton energies below 200 MeV. Our measurements are in good agreement with previously published data and offer a complete excitation function for (223,)(225)Ra in the energy range above 90 MeV. Comparison of theoretical predictions with the experimental data shows reasonable-to-good agreement. Results indicate that accelerator-based production of (225)Ac and (223)Ra below 200 MeV is a viable production method.