Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis

Abstract

Osteosarcoma (OST) is the most common bone tumor in children and adolescents with a second peak of incidence in elderly adults usually diagnosed as secondary tumors in Paget's disease or irradiated bone. Subjects with metastatic disease or whose disease relapses after the initial therapy have a poor prognosis. Moreover, multifocal OST contains tumor-initiating cells that are resistant to chemotherapy. The use of aggressive therapies in an attempt to eradicate these cells can have long-term negative consequences in these vulnerable patient populations. 227 Th-labeled molecular probes based on ligands to OST-associated receptors such as IGF-1R (insulin-like growth factor receptor 1), HER2 (human epidermal growth factor receptor 2), and PSMA (prostate-specific membrane antigen) are expected to detect and treat osseous and nonosseous sites of multifocal OST. Published reports indicate that 227 Th has limited myelotoxicity, can be stably chelated to its carriers and, as it decays at targeted sites, 227 Th produces 223 Ra that is subsequently incorporated into the areas of increased osteoblastic activity, that is, osseous metastatic lesions. Linear energy transfer of a particles emitted by 227 Th and its daughter 223 Ra is within the range of the optimum relative biological effectiveness. The radiotoxicity of a particles is virtually independent of the phase in the cell cycle, oxygenation, and the dose rate. For these reasons, even resistant OST cells remain susceptible to killing by high-energy a particles, which can also kill adjacent quiescent OST cells or cells with low expression of targeted receptors. Systemic side effects are minimized by the limited range of these intense radiations. Quantitative single-photon emission computed tomography of 227 Th and 223 Ra is feasible. Additionally, the availability of radionuclide pairs, for example, 89 Zr for positron emission tomography and 227 Th for therapy, establish a strong basis for the theranostic use of 227 Th in the individualized treatment of multifocal OST.

Actinium-225 targeted alpha particle therapy for prostate cancer

“…The TTC process involves binding the alpha-emitting Thorium-227 ( 227 Th) to a chelator, strategically linked to a monoclonal antibody (MAb) or small molecules engineered for tumor targeting 126 . 227 Th, belonging to the actinide series (half-life of 18.7 days), follows a decay scheme featuring a cascade of alpha (five alpha particles) and beta emissions, culminating in the formation of the stable isotope 207 Pb ( Figure 9 ) 127 . The alpha particle emitted during the decay of 227 Th possesses a mean energy of 5.9 MeV, contributing to a total energy of 34 MeV from all the five alpha particles in the decay series.…”

Application of Hybrid Radionuclide Imaging Technologies and Radionuclide Therapy in Patients with Osteogenic Sarcoma

“…Впоследствии применение дихлорида радия-223 стало частью рекомендаций NCCN по лечению рецидивирующей остеосаркомы. Были продемонстрированы также безопасность вводимой активности в пределах 55,5-111 кБк/ кг [39] и проникновение радия-223 через гематоэнцефалический барьер при локализации метастазов остеосаркомы в головном мозге [40]. Есть указания на то, что при лечении больных с остеосаркомой нужно увеличивать активность до 100 кБк на 1 кг массы тела [41].…”

Exploring the Potential of Nanotechnology in Pediatric Healthcare: Advances, Challenges, and Future Directions

“…These innovations aim to improve the effectiveness of treatments while minimizing potential side effects. One particularly promising treatment approach involves alpha-particle therapy utilizing (227)Th and (223)Ra, which has demonstrated efficacy in treating multifocal osteosarcoma while exhibiting limited myelotoxicity and high relative biological effectiveness [ 15 ]. Additionally, exosome mimetics derived from BMSCs offer a natural platform for nano drug delivery, delivering potent tumor inhibition activity with reduced side effects [ 16 ].…”

“…Furthermore, nanomedicines, nanoparticle-based drug delivery systems, and nanotechnological-based miRNA interventions hold promise for addressing neuroblastoma [ 9 , 10 , 11 , 12 , 13 , 14 ]. Nanotechnology also shows potential in improving outcomes for osteosarcoma treatment through alpha-particle therapy, exosome mimetics, nanocarriers, and targeted drug delivery systems [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…Disease/ConditionKey Findings Ref.Multifocal osteosarcomaAlpha-particle therapy with (227)Th and (223)Ra is a potential treatment for difficult-to-treat bone tumors due to its limited myelotoxicity and high relative biological effectiveness [15]. Exosome mimetics derived from BMSCs Natural nano drug delivery platform with potent tumor inhibition activity and fewer side effects [16].…”