Targeted alpha therapy using Radium-223: From physics to biological effects

2018 ◽  
Vol 68 ◽  
pp. 47-54 ◽  
Author(s):  
I.A. Marques ◽  
A.R. Neves ◽  
A.M. Abrantes ◽  
A.S. Pires ◽  
E. Tavares-da-Silva ◽  
...  
Keyword(s):  
Biological Effects ◽  
Targeted Alpha Therapy ◽  
Radium 223 ◽  
Alpha Therapy

scholarly journals The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis

2019 ◽  
Vol 20 (16) ◽  
pp. 3899 ◽  
Author(s):  
Mari I. Suominen ◽  
Timothy Wilson ◽  
Sanna-Maria Käkönen ◽  
Arne Scholz
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Cells ◽  
Bone Cells ◽  
Metastatic Cancer ◽  
Signal Molecules ◽  
Targeted Alpha Therapy ◽  
Radium 223 ◽  
Alpha Therapy

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metastatic cancer cells. In order to improve the prognosis of patients with bone metastases this cycle must be broken. Radium-223 dichloride (radium-223), the first targeted alpha therapy (TAT) approved, is an osteomimetic radionuclide that is incorporated into bone metastases where its high-linear energy transfer alpha radiation disrupts both the activity of bone cells and cancer cells. Therefore, radium-223 treatment has been shown preclinically to directly affect cancer cells in both osteolytic breast cancer and osteoblastic prostate cancer bone metastases as well as to inhibit the differentiation of osteoblasts and osteoclasts. Clinical studies have demonstrated an increase in survival in patients with metastatic castration-resistant prostate cancer. Due to the effectiveness and low toxicity of radium-223, several novel combination treatment strategies are currently eliciting considerable research interest.

scholarly journals Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The “Hopeful Eight”

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 906
Author(s):  
Romain Eychenne ◽  
Michel Chérel ◽  
Férid Haddad ◽  
François Guérard ◽  
Jean-François Gestin
Keyword(s):  
Production Process ◽  
Clinical Studies ◽  
Physical Characteristics ◽  
Preclinical Studies ◽  
Chemical Behavior ◽  
Targeted Alpha Therapy ◽  
Therapeutic Applications ◽  
Radium 223 ◽  
Chemical Design ◽  
Alpha Therapy

Among all existing radionuclides, only a few are of interest for therapeutic applications and more specifically for targeted alpha therapy (TAT). From this selection, actinium-225, astatine-211, bismuth-212, bismuth-213, lead-212, radium-223, terbium-149 and thorium-227 are considered as the most suitable. Despite common general features, they all have their own physical characteristics that make them singular and so promising for TAT. These radionuclides were largely studied over the last two decades, leading to a better knowledge of their production process and chemical behavior, allowing for an increasing number of biological evaluations. The aim of this review is to summarize the main properties of these eight chosen radionuclides. An overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.

scholarly journals Introduction of the targeted alpha therapy (with Radium-223) into clinical practice in Japan: learnings and implementation

2018 ◽  
Vol 33 (3) ◽  
pp. 211-221 ◽  
Author(s):  
Makoto Hosono ◽  
Hideharu Ikebuchi ◽  
Yoshihide Nakamura ◽  
Sachiko Yanagida ◽  
Seigo Kinuya
Keyword(s):  
Clinical Practice ◽  
Targeted Alpha Therapy ◽  
Radium 223 ◽  
Alpha Therapy

scholarly journals Radium-223 voor gemetastaseerd castratieresistent prostaatcarcinoom: stand van zaken en toekomstperspectief

2020 ◽  
Vol 10 (6-7) ◽  
pp. 131-140 ◽  
Author(s):  
Dirk N. J. Wyndaele
Keyword(s):  
Targeted Alpha Therapy ◽  
Radium 223 ◽  
Alpha Therapy

Samenvatting Het arsenaal aan levensverlengende systemische behandelingen voor gemetastaseerd castratieresistent prostaatcarcinoom (mCRPC) is de afgelopen jaren uitgebreid met radium-223 (Ra-223), abirateron, enzalutamide en cabazitaxel. Ra-223 is sinds 2013 in de Europese Unie als Targeted alpha Therapy (TaT) geregistreerd voor de behandeling van patiënten met mCRPC met symptomatische botmetastasen. Recente aanbevelingen van een Europese expertgroep voor de optimale inzet van alle levensverlengende behandelopties voor mCRPC geven aan dat Ra-223 een relevante optie is voor de tweede- en derdelijnsbehandeling na androgeenreceptorremmers en/of docetaxel. Dit overzichtsartikel vat deze aanbevelingen samen. Tevens wordt de praktijkervaring beschreven die de afgelopen jaren met Ra-223 is opgebouwd en wordt ingegaan op de belangrijkste recent voltooide en nog lopende klinische studies naar Ra-223 in combinatie met docetaxel, androgeenreceptorremmers, immuunmodulerende antikankermiddelen of PARP-remmers. De mogelijk toekomstige toepassing van op PSMA gerichte radioligandtherapie bij prostaatkanker wordt kort uitgelicht.

scholarly journals Revisiting the Radiobiology of Targeted Alpha Therapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Jean-Pierre Pouget ◽  
Julie Constanzo
Keyword(s):  
Biological Effects ◽  
Dna Lesions ◽  
Alpha Particles ◽  
Systemic Effects ◽  
X Rays ◽  
Castration Resistant Prostate Cancer ◽  
Bystander Effects ◽  
Targeted Alpha Therapy ◽  
Alpha Emitter ◽  
Alpha Therapy

Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of 223RaCl2 for patients with metastatic castration-resistant prostate cancer and the development of several alpha emitter-based radiopharmaceuticals. It is acknowledged that alpha particles are highly cytotoxic because they produce complex DNA lesions. Hence, the nucleus is considered their critical target, and many studies did not report any effect in other subcellular compartments. Moreover, their physical features, including their range in tissues (<100 μm) and their linear energy transfer (50–230 keV/μm), are well-characterized. Theoretically, TAT is indicated for very small-volume, disseminated tumors (e.g., micrometastases, circulating tumor cells). Moreover, due to their high cytotoxicity, alpha particles should be preferred to beta particles and X-rays to overcome radiation resistance. However, clinical studies showed that TAT might be efficient also in quite large tumors, and biological effects have been observed also away from irradiated cells. These distant effects are called bystander effects when occurring at short distance (<1 mm), and systemic effects when occurring at much longer distance. Systemic effects implicate the immune system. These findings showed that cells can die without receiving any radiation dose, and that a more complex and integrated view of radiobiology is required. This includes the notion that the direct, bystander and systemic responses cannot be dissociated because DNA damage is intimately linked to bystander effects and immune response. Here, we provide a brief overview of the paradigms that need to be revisited.

Nanoconstructs in Targeted Alpha-Therapy

2015 ◽  
Vol 4 (2) ◽  
pp. 71-76 ◽  
Author(s):  
Jan Kozempel ◽  
Martin Vlk
Keyword(s):  
Targeted Alpha Therapy ◽  
Alpha Therapy
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