Targeted alpha therapy and its role in a modern nuclear medicine
Authors:
Petra Suchánková 1; Jaroslav Červenák 2,3; Ján Kozempel 1; Martin Vlk 1
Authors‘ workplace:
Fakulta jaderná a fyzikálně inženýrská, Katedra jaderné chemie, České vysoké učení technické v Praze, ČR
1; Ústav jaderné fyziky Akademie věd České republiky, v. v. i., Husinec-Řež, ČR
2; Všeobecná fakultní nemocnice v Praze, ČR
3
Published in:
NuklMed 2018;7:7-13
Category:
Review Article
Overview
Aim:
Summary of the development of therapy using radionuclides and potential of alpha radionuclides in targeted therapy.
Introduction:
The interest aimed on radionuclides emitting alpha particles is constantly growing in nuclear medicine. In the case of targeted alpha therapy, not only radionuclides decaying by one or several alphas are used, but also the suitable carriers for these radionuclides are developed and could be used as radiopharmaceuticals.
Material:
Since 1908, less than ten years after its discovery, radium had been used in medicine mainly to treat skin diseases. Since then therapy using radionuclides has gone a long way – from radium-226, through electron emitters, 211At, to nuclides forming short-lived decay chains known as in vivo generators, e.g. 225Ac, 213Bi or 223Ra.
The advantage of alpha therapy is the release of a high energy in a small volume, which leads to lower radiation exposure of surrounding tissues. Due to the high LET of alpha particles, double-strand breaks of DNA molecules, which are lethal for the cell, are formed. For this reason, the carriers of alpha radionuclides should resist to the high released energy, in order to prevent its radiolysis. The stabilisation of reflected daughter nuclide is also important because of its release into surrounding tissue and thus its damage. Among studied carriers of alpha radionuclides inorganic nanomaterials dominate, e.g. iron, titanium or gold oxide nanoparticles or hydroxyapatite.
Conclusions:
The research in the field of targeted alpha therapy opens the way to treatment of some types of cancerous diseases and especially the increase of patients’ life quality and its extension. Therefore, the effort to prepare new radionuclides should continue, suitable both for early diagnosis and subsequent therapy. Particular attention should also be given to the therapeutic radionuclide carriers, best suited to the theranostic concept, with regard to their chemical and radiation stability and availability.
Key Words:
alpha radionuclides, 223Ra, carriers, nanoparticles, targeted therapy, theranostics
Sources
1. Běhounek F. Radium a paprsky X (Tajemství hmoty a energie). Praha, Šolc a Šimáček, Nakladatelská společnost s r. o. 1924, 174 p
2. Bayounes O, Souffrin C, Meunier D La radium: découverte, utilisation et danger; [online]. 2013. [cit. 1. 9. 2015]. Dostupné na: http://culturesciences.chimie.ens.fr/content/le-radium-découverte-utilisation-et-danger.
3. Curiová E. Paní Curiová. Praha, vyd. Mladá fronta, nakladatelství Máj, 1964, 320 p
4. Zalutsky MR, Reardonb DA, Pozzia OR et al. Targeted α-Particle Radiotherapy with 211At-labeled Monoclonal Antibodies. Nucl Med Biol. 2007;34:779-785
5. Zalutsky MR, Reardon DA, Akabani G, et al. Clinical Experience with α-Particle–Emitting 211At: Treatment of Recurrent Brain Tumor Patients with 211At-Labeled Chimeric Antitenascin Monoclonal Antibody 81C6. J Nucl Med. 2008;49:30-38
6. Kozempel J, Vlk M. Nanoconstructs in Tagreted Alpha-Therapy. Recent Patents on Nanomedicine 2014;4:71-76
7. Humm JL. Dosimetric Aspect of Radiolabeled Antibodies for Tumor Therapy. J Nucl Med. 1986;27:1490-1497
8. Vértes A, Nagy S, Klencsár Z, et al. Handbook of Nuclear Chemistry, Heidelberg, Springer Sciences Business Media B.V. 2011, 389 p
9. Shishkin DN, Krupitskii SV, Kuznetsov SA. Extraction Generator of Ra-223 for Nuclear Medicine, Radiochemistry, 2011;53:404-406
10. Steyn GF, Vermeulen C, Szelecsenyi F et al. Cross sections of proton-induced reactions on 152Gd, 155Gd and 159Tb with emphasis on the production of selected Tb radionuclides. Nucl Instrum Methods Phys Res B. 2014;319:128-140
11. Morgenstern A, Lebeda O, Stursa J, et al. Production of U-230/Th-226 for Targeted Alpha Therapy via Proton Irradiation of Pa-231, Anal. Chem. 2008;80:8763-8770
12. NuDat 2.6 National Nuclear Data Center, Brookhaven National Laboratory; [online]. [cit. 1. 4. 2016]. Dostupné na: www.nndc.bnl.gov/nudat2/.
13. Andersson H, Elqqvist J, Horvath G et al. Astatine-211-labeled Antibodies for Treatment of Disseminated Ovarian Cancer: An Overview of Results in an Ovarian Tumor Model. Clin Cancer Res. 2003;9:3914-3921
14. Andersson H, Palm S, Lindegren S et al. Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer. Anticancer Res. 2001;21:409-412
15. Apostolidis C, Molinet R, McGinley J et al. Cyclotron production of Ac-225 for targeted alpha therapy. Appl Radiat Isot. 2005;62:383-387
16. U.S. National Institutes of health. Low Dose Cytarabine and Lintuzumab-Ac-225 in Older AML Patients. Ident. No.: NCT02575963
17. U.S. National Institutes of health. Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies. Ident. No.: NCT00672165
18. Kratochwil C, Bruchertseifer F, Giesel FL et al. 225Ac-PMSA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. J Nucl Med 2016;57:1941-1944
19. Meredith R F, Torgue J, Shen S et al. Pharmacokinetics and Imaging of 212Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients. Cancer Biotherapy & Radiopharmaceuticals. 2014;29:12-17
20. Sgouros G, Ballangrud AM, Jurcic JG et al. Pharmacokinetics and Dosimetry of an α-Particle Emitter Labeled Antibody: 213Bi-HuM195 (Anti-CD33) in Patients with Leukemia. J Nucl Med. 1999;40:1935-1946
21. Kozempel J, Vlk M, Málková E et al. Prospective carriers of Ra-223 for targeted alpha particle therapy. J Radioanal Nucl Chem. 2014;34:443-447
22. EMA: Xofigo (radium Ra-223 dichloride) [online]. 2017. [cit. 2. 1. 2016]. Dostupné na: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002653/human_med_001692.jsp&mid=WC0b01ac058001d124.
23. Etchebehere EC, Milton DR, Araujo JC et al. Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution. Eur J Nucl Med Mol Imaging. 2016;43:8-20
24. Rojas JV, Woodward JD, Chen N et al. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy. Nucl Med Biol. 2015;42:614-620
25. Piotrowska A, Leszczuk E, Bruchertseifer F et al. Functionalized NaA nanozeolites labeled with 224,225Ra for targeted alpha therapy. J Nanopart Res. 2013;15:2082-2092
26. Mokhodoeva O, Vlk M, Málková E et al. Study of 223Ra uptake mechanism by Fe3O4 nanoparticles: towards new prospective theranostic SPIONs. J Nanopart Res 2016;18:301
27. Matsumura Y, Maeda H. A new Concept for Macromolecular therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Research 1986;46:6387-6392
28. Maeda H, Tsukigawa K, Fang J et al. A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next-Generation chemotherapeutics and Photodynamic Therapy – Problems, Solutions and Prospects. Microcirculation. 2016;23:173-182
29. Van Butsele K, Jérôme R, Jérôme C. Functional amphiphilic and biodegradable copolymers for intravenous vectorisation. Polymer. 2007;48:7431-7443
30. Patra Ch R, Bhattacharya R, Mukhopadhyay D. et al. Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer. Advanced Drug Delivery Reviews 2010;62:346-361
31. Janiszewska Ł, Koźmiński P, Pruszyński M. et al. Gold Nanoparticle-Substance P(5-11) Conjugate as a Carrier for 211At in Alpha Particle Therapy. Abstrakt – 9th Symposium on Targeted Alpha Therapy, Varšava, Polsko (2015)
32. Kučka J, Hrubý M, Koňák Č. et al. Astatination of nanoparticles containing silver as possible carriers of 211At. Applied Radiation and Isotopes. 2006;64:201-206
Labels
Paediatric radiology Nuclear medicine Clinical oncology Radiodiagnostics RadiotherapyArticle was published in
Nuclear Medicine
2018 Issue 1
Most read in this issue
- Targeted alpha therapy and its role in a modern nuclear medicine
- Influence of a department monitoring to the staff radiation exposure at a PET department
- Vascular malformation of the face detected on a bone scan