Targeted alpha-particle therapy (or TAT) is an in-development method of targeted radionuclide therapy of various cancers. It employs radioactive substances which undergo alpha decay to treat diseased tissue at close proximity.[1] It has the potential to provide highly targeted treatment, especially to microscopic tumour cells. Targets include leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis.[2] As in diagnostic nuclear medicine, appropriate radionuclides can be chemically bound to a targeting biomolecule which carries the combined radiopharmaceutical to a specific treatment point.[3]
It has been said that "α-emitters are indispensable with regard to optimisation of strategies for tumour therapy".[4]
Advantages of alpha emitters
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/2/28/SEM_-_range_of_%CE%B1_and_%CE%B2%E2%88%92_particles.jpg/220px-SEM_-_range_of_%CE%B1_and_%CE%B2%E2%88%92_particles.jpg)
The primary advantage of alpha particle (α) emitters over other types of radioactive sources is their very high linear energy transfer (LET) and relative biological effectiveness (RBE).[5] Beta particle (β) emitters such as yttrium-90 can travel considerable distances beyond the immediate tissue before depositing their energy, while alpha particles deposit their energy in 70–100 μm long tracks.[6]
Alpha particles are more likely than other types of radiation to cause double-strand breaks to DNA molecules, which is one of several effective causes of cell death.[7][8]
Production
[edit]Some α emitting isotopes such as 225Ac and 213Bi are only available in limited quantities from 229Th decay, although cyclotron production is feasible.[9][10][11] Among alpha-emitting radiometals according to availability, chelation chemistry, and half-life, 212Pb is also a promising candidate for targeted alpha-therapy.[12][13]
The ARRONAX cyclotron can produce 211At by irradiation of 209Bi.[14][9]
Applications
[edit]Though many α-emitters exist, useful isotopes would have a sufficient energy to cause damage to cancer cells, and a half-life that is long enough to provide a therapeutic dose without remaining long enough to damage healthy tissue.
Immunotherapy
[edit]Several radionuclides have been studied for use in immunotherapy. Though β-emitters are more popular, in part due to their availability, trials have taken place involving 225Ac, 211At, 212Pb and 213Bi.[9]
Peritoneal carcinomas
[edit]Treatment of peritoneal carcinomas has promising early results limited by availability of α-emitters compared to β-emitters.[4]
Bone metastases
[edit]223Ra was the first α-emitter approved by the FDA in the United States for treatment of bone metastases from prostate cancer, and is a recommended treatment in the UK by NICE.[3][15] In a phase III trial comparing 223Ra to a placebo, survival was significantly improved.[16]
Leukaemia
[edit]Early trials of 225Ac and 213Bi have shown evidence of anti-tumour activity in Leukaemia patients.[17]
Melanomas
[edit]Phase I trials on melanomas have shown 213Bi is effective in causing tumour regression.[18][19]
Solid tumours
[edit]The short path length of alpha particles in tissue, which makes them well suited to treatment of the above types of disease, is a negative when it comes to treatment of larger bodies of solid tumour by intravenous injection.[20][21] Potential methods to solve this problem of delivery exist, such as direct intratumoral injection[22] and anti-angiogenic drugs.[23][3] Limited treatment experience of low grade malignant gliomas has shown possible efficacy.[24]
See also
[edit]References
[edit]- ^ "Targeted Radionuclide Therapy". Advancing nuclear medicine through innovation. Washington, D.C.: National Academies Press. 2007. doi:10.17226/11985. ISBN 978-0-309-11067-9. PMID 20669430.
- ^ Mulford, DA; Scheinberg, DA; Jurcic, JG (January 2005). "The promise of targeted {alpha}-particle therapy". Journal of Nuclear Medicine. 46 (Suppl 1): 199S–204S. PMID 15653670.
- ^ a b c Dekempeneer, Yana; Keyaerts, Marleen; Krasniqi, Ahmet; Puttemans, Janik; Muyldermans, Serge; Lahoutte, Tony; D’huyvetter, Matthias; Devoogdt, Nick (19 May 2016). "Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle". Expert Opinion on Biological Therapy. 16 (8): 1035–1047. doi:10.1080/14712598.2016.1185412. PMC 4940885. PMID 27145158.
- ^ a b Seidl, Christof; Senekowitsch-Schmidtke, Reingard (2011). "Targeted Alpha Particle Therapy of Peritoneal Carcinomas". In Baum, Richard P. (ed.). Therapeutic nuclear medicine. Berlin: Springer. pp. 557–567. doi:10.1007/174_2012_678. ISBN 978-3-540-36718-5.
- ^ Kane, Suzanne Amador (2003). Introduction to physics in modern medicine (Repr. ed.). London: Taylor & Francis. p. 243. ISBN 9780415299633.
- ^ Elgqvist, Jörgen; Frost, Sofia; Pouget, Jean-Pierre; Albertsson, Per (2014). "The Potential and Hurdles of Targeted Alpha Therapy – Clinical Trials and Beyond". Frontiers in Oncology. 3: 324. doi:10.3389/fonc.2013.00324. PMC 3890691. PMID 24459634.
- ^ Baum, Richard P (2014). Therapeutic Nuclear Medicine. Heidelberg: Springer. p. 98. ISBN 9783540367192.
- ^ Hodgkins, Paul S.; O'Neill, Peter; Stevens, David; Fairman, Micaela P. (December 1996). "The Severity of Alpha-Particle-Induced DNA Damage Is Revealed by Exposure to Cell-Free Extracts". Radiation Research. 146 (6): 660–7. Bibcode:1996RadR..146..660H. doi:10.2307/3579382. JSTOR 3579382. PMID 8955716.
- ^ a b c Seidl, Christof (April 2014). "Radioimmunotherapy with α-particle-emitting radionuclides". Immunotherapy. 6 (4): 431–458. doi:10.2217/imt.14.16. PMID 24815783.
- ^ Apostolidis, C.; Molinet, R.; McGinley, J.; Abbas, K.; Möllenbeck, J.; Morgenstern, A. (March 2005). "Cyclotron production of Ac-225 for targeted alpha therapy". Applied Radiation and Isotopes. 62 (3): 383–387. doi:10.1016/j.apradiso.2004.06.013. PMID 15607913.
- ^ Miederer, Matthias; Scheinberg, David A.; McDevitt, Michael R. (September 2008). "Realizing the potential of the Actinium-225 radionuclide generator in targeted alpha particle therapy applications". Advanced Drug Delivery Reviews. 60 (12): 1371–1382. doi:10.1016/j.addr.2008.04.009. PMC 3630456. PMID 18514364.
- ^ Kokov, K.V.; Egorova, B.V.; German, M.N.; Klabukov, I.D.; Krasheninnikov, M.E.; Larkin-Kondrov, A.A.; Makoveeva, K.A.; Ovchinnikov, M.V.; Sidorova, M.V.; Chuvilin, D.Y. (2022). "212Pb: Production Approaches and Targeted Therapy Applications". Pharmaceutics. 14 (1): 189. doi:10.3390/pharmaceutics14010189. ISSN 1999-4923. PMC 8777968. PMID 35057083.
- ^ Yang, Hua; Wilson, Justin J.; Orvig, Chris; Li, Yawen; Wilbur, D. Scott; Ramogida, Caterina F.; Radchenko, Valery; Schaffer, Paul (2022). "Harnessing α-Emitting Radionuclides for Therapy: Radiolabeling Method Review". Journal of Nuclear Medicine. 63 (1): 5–13. doi:10.2967/jnumed.121.262687. ISSN 1535-5667. PMC 8717181. PMID 34503958.
- ^ Haddad, Ferid; Barbet, Jacques; Chatal, Jean-Francois (1 July 2011). "The ARRONAX Project". Current Radiopharmaceuticals. 4 (3): 186–196. doi:10.2174/1874471011104030186. PMID 22201708.
- ^ "Radium-223 dichloride for treating hormone-relapsed prostate cancer with bone metastases". National Institute for Health and Care Excellence. 28 September 2016. Retrieved 19 December 2016.
- ^ Parker, C.; Nilsson, S.; Heinrich, D.; Helle, S.I.; O'Sullivan, J.M.; Fosså, S.D.; Chodacki, A.; Wiechno, P.; Logue, J.; Seke, M.; Widmark, A.; Johannessen, D.C.; Hoskin, P.; Bottomley, D.; James, N.D.; Solberg, A.; Syndikus, I.; Kliment, J.; Wedel, S.; Boehmer, S.; Dall'Oglio, M.; Franzén, L.; Coleman, R.; Vogelzang, N.J.; O'Bryan-Tear, C.G.; Staudacher, K.; Garcia-Vargas, J.; Shan, M.; Bruland, Ø.S.; Sartor, O. (18 July 2013). "Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer". New England Journal of Medicine. 369 (3): 213–223. doi:10.1056/NEJMoa1213755. PMID 23863050.
- ^ Jurcic, Joseph G.; Rosenblat, Todd L. (2014). "Targeted Alpha-Particle Immunotherapy for Acute Myeloid Leukemia". American Society of Clinical Oncology Educational Book. 34 (34): e126–e131. doi:10.14694/EdBook_AM.2014.34.e126. PMID 24857092.
- ^ Allen, Barry J; Raja, Chand; Rizvi, Syed; Li, Yong; Tsui, Wendy; Zhang, David; Song, Emma; Qu, Chang Fa; Kearsley, John; Graham, Peter; Thompson, John (21 August 2004). "Targeted alpha therapy for cancer". Physics in Medicine and Biology. 49 (16): 3703–3712. Bibcode:2004PMB....49.3703A. doi:10.1088/0031-9155/49/16/016. PMID 15446799. S2CID 250862050.
- ^ Kim, Young-Seung; Brechbiel, Martin W. (6 December 2011). "An overview of targeted alpha therapy". Tumor Biology. 33 (3): 573–590. doi:10.1007/s13277-011-0286-y. PMC 7450491. PMID 22143940.
- ^ Larson, Steven M.; Carrasquillo, Jorge A.; Cheung, Nai-Kong V.; Press, Oliver W. (22 May 2015). "Radioimmunotherapy of human tumours". Nature Reviews Cancer. 15 (6): 347–360. doi:10.1038/nrc3925. PMC 4798425. PMID 25998714.
- ^ Sofou, S (2008). "Radionuclide carriers for targeting of cancer". International Journal of Nanomedicine. 3 (2): 181–99. doi:10.2147/ijn.s2736. PMC 2527672. PMID 18686778.
- ^ Arazi, L; Cooks, T; Schmidt, M; Keisari, Y; Kelson, I (21 August 2007). "Treatment of solid tumors by interstitial release of recoiling short-lived alpha emitters". Physics in Medicine and Biology. 52 (16): 5025–5042. Bibcode:2007PMB....52.5025A. doi:10.1088/0031-9155/52/16/021. PMID 17671351. S2CID 1585204.
- ^ Huang, Chen-Yu; Pourgholami, Mohammad H.; Allen, Barry J. (November 2012). "Optimizing radioimmunoconjugate delivery in the treatment of solid tumor". Cancer Treatment Reviews. 38 (7): 854–860. doi:10.1016/j.ctrv.2011.12.005. PMID 22226242.
- ^ Cordier, Dominik; Krolicki, Leszek; Morgenstern, Alfred; Merlo, Adrian (May 2016). "Targeted Radiolabeled Compounds in Glioma Therapy". Seminars in Nuclear Medicine. 46 (3): 243–249. doi:10.1053/j.semnuclmed.2016.01.009. PMID 27067505.
Well, that’s interesting to know that Psilotum nudum are known as whisk ferns. Psilotum nudum is the commoner species of the two. While the P. flaccidum is a rare species and is found in the tropical islands. Both the species are usually epiphytic in habit and grow upon tree ferns. These species may also be terrestrial and grow in humus or in the crevices of the rocks.
View the detailed Guide of Psilotum nudum: Detailed Study Of Psilotum Nudum (Whisk Fern), Classification, Anatomy, Reproduction