Radionuclide therapy explained

Radionuclide therapy

Radionuclide therapy (RNT, also known as unsealed source radiotherapy or molecular radiotherapy) uses radioactive substances called radiopharmaceuticals to treat medical conditions, particularly cancer. These are introduced into the body by various means (injection or ingestion are the two most commonplace) and localise to specific locations, organs or tissues depending on their properties and administration routes. This includes anything from a simple compound such as sodium iodide that locates to the thyroid via trapping the iodide ion, to complex biopharmaceuticals such as recombinant antibodies which are attached to radionuclides and seek out specific antigens on cell surfaces.[1] [2]

This is a type of targeted therapy which uses the physical, chemical and biological properties of the radiopharmaceutical to target areas of the body for radiation treatment.[3] The related diagnostic modality of nuclear medicine employs the same principles but uses different types or quantities of radiopharmaceuticals in order to image or analyse functional systems within the patient.

RNT contrasts with sealed-source therapy (brachytherapy) where the radionuclide remains in a capsule or metal wire during treatment and needs to be physically placed precisely at the treatment position.[4]

When the radionuclides are ligands (such as with Lutathera and Pluvicto), the technique is also known as radioligand therapy.[5]

Clinical use

Thyroid conditions

Iodine-131 (131I) is the most common RNT worldwide and uses the simple compound sodium iodide with a radioactive isotope of iodine. The patient (human or animal) may ingest an oral solid or liquid amount or receive an intravenous injection of a solution of the compound. The iodide ion is selectively taken up by the thyroid gland. Both benign conditions like thyrotoxicosis and certain malignant conditions like papillary thyroid cancer can be treated with the radiation emitted by radioiodine.[6] Iodine-131 produces beta and gamma radiation. The beta radiation released damages both normal thyroid tissue and any thyroid cancer that behaves like normal thyroid in taking up iodine, so providing the therapeutic effect, whilst most of the gamma radiation escapes the patient's body.[7]

Most of the iodine not taken up by thyroid tissue is excreted through the kidneys into the urine. After radioiodine treatment the urine will be radioactive or 'hot', and the patients themselves will also emit gamma radiation. Depending on the amount of radioactivity administered, it can take several days for the radioactivity to reduce to the point where the patient does not pose a radiation hazard to bystanders. Patients are often treated as inpatients and there are international guidelines, as well as legislation in many countries, which govern the point at which they may return home.[8]

Bone metastasis

See also: Targeted alpha-particle therapy. Radium-223 chloride, strontium-89 chloride and samarium-153 EDTMP are used to treat secondary cancer in the bones.[9] [10] Radium and strontium mimic calcium in the body.[11] Samarium is bound to tetraphosphate EDTMP, phosphates are taken up by osteoblastic (bone forming) repairs that occur adjacent to some metastatic lesions.[12]

Bone marrow conditions

Beta emitting phosphorus-32 (32P), as sodium phosphate, is used to treat overactive bone marrow, in which it is otherwise naturally metabolised.[13] [14] [15]

Joint inflammation

Yttrium-90 colloid

An yttrium-90 (90Y) colloidal suspension is used for radiosynovectomy in the knee joint.[16]

Liver tumours

Yttrium-90 spheres

See main article: Selective internal radiation therapy. 90Y in the form of a resin or glass spheres can be used to treat primary and metastic liver cancers.[17]

Neuroendocrine tumours

Iodine-131 mIBG

131I-mIBG (metaiodobenzylguanidine) is used for the treatment of phaeochromocytoma and neuroblastoma.[18]

Lutetium-177

See also: Peptide receptor radionuclide therapy. 177Lu is bound with a DOTA chelator to target neuroendocrine tumours.[19]

Experimental antibody based methods

At the Institute for Transuranium Elements (ITU) work is being done on alpha-immunotherapy, this is an experimental method where antibodies bearing alpha isotopes are used. Bismuth-213 is one of the isotopes which has been used. This is made by the alpha decay of actinium-225. The generation of one short-lived isotope from longer lived isotope is a useful method of providing a portable supply of a short-lived isotope. This is similar to the generation of technetium-99m by a technetium generator. The actinium-225 is made by the irradiation of radium-226 with a cyclotron.[20]

Notes and References

  1. Buscombe. J.. Navalkissoor. S.. Molecular radiotherapy. Clinical Medicine. 1 August 2012. 12. 4. 381–386. 10.7861/clinmedicine.12-4-381. 22930888. 4952132. free.
  2. Volkert . Wynn A. . Hoffman . Timothy J. . Therapeutic Radiopharmaceuticals . Chemical Reviews . 99 . 9 . 1999 . 2269–2292 . 10.1021/cr9804386 . 11749482.
  3. Book: Nicol. Alice. Waddington. Wendy. Dosimetry for radionuclide therapy. 2011. Institute of Physics and Engineering in Medicine. York. 9781903613467.
  4. Book: Elizabeth A. Martin. Tanya A. McFerran. A dictionary of nursing. 2014. Oxford University Press. Oxford. 9780199666379. 6th. 10.1093/acref/9780199666379.001.0001.
  5. https://www.cnbc.com/2023/02/11/radioligand-cancer-therapy-forces-manufacturers-to-race-the-clock.html Radioligand therapy, a ‘game-changer’ for cancer treatment, forces manufacturers to race against a ticking clock
  6. Silberstein. E. B.. Alavi. A.. Balon. H. R.. Clarke. S. E. M.. Divgi. C.. Gelfand. M. J.. Goldsmith. S. J.. Jadvar. H.. Marcus. C. S.. Martin. W. H.. Parker. J. A.. Royal. H. D.. Sarkar. S. D.. Stabin. M.. Waxman. A. D.. The SNMMI Practice Guideline for Therapy of Thyroid Disease with 131I 3.0. Journal of Nuclear Medicine. 11 July 2012. 53. 10. 1633–1651. 10.2967/jnumed.112.105148. 22787108. free.
  7. Book: IAEA. Manual on therapeutic uses of iodine-131. 1996. International Atomic Energy Agency. Vienna. 7.
  8. Book: IAEA. ICRP. Release of patients after radionuclide therapy. 2009. International Atomic Energy Agency. Vienna, Austria. 978-92-0-108909-0.
  9. Den. RB. Doyle. LA. Knudsen. KE. Practical guide to the use of radium 223 dichloride.. The Canadian Journal of Urology. April 2014. 21. 2 Supp 1. 70–6. 24775727.
  10. Lutz. Stephen. Berk. Lawrence. Chang. Eric. Chow. Edward. Hahn. Carol. Hoskin. Peter. Howell. David. Konski. Andre. Kachnic. Lisa. Lo. Simon. Sahgal. Arjun. Silverman. Larry. von Gunten. Charles. Mendel. Ehud. Vassil. Andrew. Bruner. Deborah Watkins Bruner. Deborah Watkins. Hartsell. William. Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline. International Journal of Radiation Oncology, Biology, Physics. March 2011. 79. 4. 965–976. 10.1016/j.ijrobp.2010.11.026. 21277118. free.
  11. Goyal. Jatinder. Antonarakis. Emmanuel S.. Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases. Cancer Letters. October 2012. 323. 2. 135–146. 10.1016/j.canlet.2012.04.001. 4124611. 22521546.
  12. Serafini. AN. Samarium Sm-153 lexidronam for the palliation of bone pain associated with metastases.. Cancer. 15 June 2000. 88. 12 Suppl. 2934–9. 10.1002/1097-0142(20000615)88:12+<2934::AID-CNCR9>3.0.CO;2-S. 10898337. 45863868 .
  13. Tennvall. Jan. Brans. Boudewijn. EANM procedure guideline for 32P phosphate treatment of myeloproliferative diseases. European Journal of Nuclear Medicine and Molecular Imaging. 30 March 2007. 34. 8. 1324–1327. 10.1007/s00259-007-0407-4. 17396258. 21759615.
  14. Book: Raj. Gurdeep. Advanced Inorganic Chemistry Vol 1. Krishna Prakashan Media. 9788187224037. 497. en.
  15. Book: Gropper. Sareen S.. Smith. Jack L.. Advanced Nutrition and Human Metabolism. Cengage Learning. 978-1133104056. 432. en. 2012-06-01.
  16. Siegel. Michael E.. Siegel. Herrick J.. Luck. James V.. Radiosynovectomy's clinical applications and cost effectiveness: A review. Seminars in Nuclear Medicine. October 1997. 27. 4. 364–371. 10.1016/S0001-2998(97)80009-8. 9364646.
  17. Allen. Theresa M.. Ligand-targeted therapeutics in anticancer therapy. Nature Reviews Cancer. October 2002. 2. 10. 750–763. 10.1038/nrc903. 12360278. 21014917.
  18. Sharp. Susan E.. Trout. Andrew T.. Weiss. Brian D.. Gelfand. Michael J.. MIBG in Neuroblastoma Diagnostic Imaging and Therapy. RadioGraphics. January 2016. 36. 1. 258–278. 10.1148/rg.2016150099. 26761540.
  19. Maqsood . Muhammad Haisum . Tameez Ud Din . Asim . Khan . Ameer H . Neuroendocrine Tumor Therapy with Lutetium-177: A Literature Review . Cureus . 30 January 2019 . 11 . 1 . e3986 . 10.7759/cureus.3986 . 30972265 . 6443107. free.
  20. Morgenstern. Alfred. Bruchertseifer. Frank. Apostolidis. Christos. Bismuth-213 and Actinium-225 – Generator Performance and Evolving Therapeutic Applications of Two Generator-Derived Alpha-Emitting Radioisotopes. Current Radiopharmaceuticals. 1 June 2012. 5. 3. 221–227. 10.2174/1874471011205030221. 22642390.

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