scholarly journals 212Pb: Production Approaches and Targeted Therapy Applications

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 189
Author(s):  
Konstantin V. Kokov ◽  
Bayirta V. Egorova ◽  
Marina N. German ◽  
Ilya D. Klabukov ◽  
Michael E. Krasheninnikov ◽  
...  

Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of 10.64 h, and daughter alpha-emitter short-lived 212Bi (T1/2 = 1 h), provides the possibility for the synthesis and purification of complex radiopharmaceuticals with minimum loss of radioactivity during preparation. As a benefit for clinical implementation, it can be milked from a radionuclide generator in different ways. The main approaches applied for these purposes are considered and described in this review, including chromatographic, solution, and other techniques to isolate 212Pb from its parent radionuclide. Furthermore, molecules used for lead’s binding and radiochemical features of preparation and stability of compounds labeled with 212Pb are discussed. The results of preclinical studies with an estimation of therapeutic and tolerant doses as well as recently initiated clinical trials of targeted radiopharmaceuticals are presented.

Author(s):  
Tadashi Watabe ◽  
Makoto Hosono ◽  
Seigo Kinuya ◽  
Takahiro Yamada ◽  
Sachiko Yanagida ◽  
...  

AbstractWe present the guideline for use of [211At] sodium astatide (NaAt) for targeted alpha therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on 8th Feb, 2021. The study showed that patients receiving [211At]NaAt do not need to be admitted to a radiotherapy room and outpatient treatment is possible. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers. Precautions for patients and their families, safety management associated with the use of [211At]NaAt, education and training, and disposal of medical radioactive contaminants are also included in this guideline. Treatment using [211At]NaAt in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection and evaluation methodology shown here are considered internationally useful as well.


2008 ◽  
Vol 1 (3) ◽  
pp. 240-250 ◽  
Author(s):  
Barry Allen ◽  
Chand Raja ◽  
Syed Rizvi ◽  
Peter Graham ◽  
John Kearsley

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1974
Author(s):  
Falco Reissig ◽  
David Bauer ◽  
Kristof Zarschler ◽  
Zbynek Novy ◽  
Katerina Bendova ◽  
...  

Currently, targeted alpha therapy is one of the most investigated topics in radiopharmaceutical cancer management. Especially, the alpha emitter 225Ac has excellent nuclear properties and is gaining increasing popularity for the treatment of various tumor entities. We herein report on the synthesis of two universal 225Ac-chelators for mild condition radiolabeling and binding to conjugate molecules of pharmacological interest via the copper-mediated click chemistry. A convenient radiolabeling procedure was investigated as well as the complex stability proved for both chelators and two PSMA (prostate-specific membrane antigen)-targeting model radioconjugates. Studies regarding affinity and cell survival were performed on LNCaP cells followed by biodistribution studies, which were performed using LNCaP tumor-bearing mice. High efficiency radiolabeling for all conjugates was demonstrated. Cell binding studies revealed a fourfold lower cell affinity for the PSMA radioconjugate with one targeting motif compared to the radioconjugate owing two targeting motifs. Additionally, these differences were verified by in vitro cell survival evaluation and biodistribution studies, both showing a higher cell killing efficiency for the same dose, a higher tumor uptake (15%ID/g) and a rapid whole body clearance after 24 h. The synthesized chelators will overcome obstacles of lacking stability and worse labeling needs regarding 225Ac complexation using the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid) chelator. Moreover, the universal functionalization expands the coverage of these chelators in combination with any sensitive bio(macro)molecule, thus improving treatment of any addressable tumor target.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 906
Author(s):  
Romain Eychenne ◽  
Michel Chérel ◽  
Férid Haddad ◽  
François Guérard ◽  
Jean-François Gestin

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.


2014 ◽  
Vol 3 ◽  
Author(s):  
Jörgen Elgqvist ◽  
Sofia Frost ◽  
Jean-Pierre Pouget ◽  
Per Albertsson

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 49
Author(s):  
Bryce Nelson ◽  
Jan Andersson ◽  
Frank Wuest

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinical trials; and an outlook on the future of TAT.


2001 ◽  
Vol 3 (5) ◽  
pp. 345-353 ◽  
Author(s):  
S. M. A. Rizvi ◽  
B. J. Allen ◽  
Z. Tian ◽  
G. Goozee ◽  
S. Sarkar

2021 ◽  
Vol 252 ◽  
pp. 03002
Author(s):  
S.J. Yennello ◽  
L.A McIntosh ◽  
J.D. Burns ◽  
E.E. Tereshatov ◽  
G. Tabacaru ◽  
...  

Alpha emitting radionuclides with medically relevant half-lives are interesting for treatment of tumors and other diseases because they deposit large amounts of energy close to the location of the radioisotope. Researchers at the Cyclotron Institute at Texas A&M University are developing a program to produce 211At, an alpha emitter with a medically relevant half-life. The properties of 211At make it a great candidate for targeted alpha therapy for cancer due to its short half-life (7.2 h). Astatine-211 has now been produced multiple times and reliability of this process is being improved.


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