Radionuclide therapy

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Radionuclide therapy
ICD-9-CM 92.28

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]

Contents

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

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

90Y in the form of a resin or glass spheres can be used to treat primary and metastatic liver cancers. [17]

Neuroendocrine tumours

Iodine-131 mIBG

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

Lutetium-177

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]

Related Research Articles

<span class="mw-page-title-main">Radiation therapy</span> Therapy using ionizing radiation, usually to treat cancer

Radiation therapy or radiotherapy is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.

<span class="mw-page-title-main">Nuclear medicine</span> Medical specialty

Nuclear medicine, or nucleology, is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, radiology done inside out, because it records radiation emitted from within the body rather than radiation that is transmitted through the body from external sources like X-ray generators. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a physiological imaging modality. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans are the two most common imaging modalities in nuclear medicine.

A radioligand is a microscopic particle which consists of a therapeutic radioactive isotope and the cell-targeting compound - the ligand. The ligand is the target binding site, it may be on the surface of the targeted cancer cell for therapeutic purposes. Radioisotopes can occur naturally or be synthesized and produced in a cyclotron/nuclear reactor. The different types of radioisotopes include Y-90, H-3, C-11, Lu-177, Ac-225, Ra-223, In-111, I-131, I-125, etc. Thus, radioligands must be produced in special nuclear reactors for the radioisotope to remain stable. Radioligands can be used to analyze/characterize receptors, to perform binding assays, to help in diagnostic imaging, and to provide targeted cancer therapy. Radiation is a novel method of treating cancer and is effective in short distances along with being unique/personalizable and causing minimal harm to normal surrounding cells. Furthermore, radioligand binding can provide information about receptor-ligand interactions in vitro and in vivo. Choosing the right radioligand for the desired application is important. The radioligand must be radiochemically pure, stable, and demonstrate a high degree of selectivity, and high affinity for their target.

<span class="mw-page-title-main">Nuclear fission product</span> Atoms or particles produced by nuclear fission

Nuclear fission products are the atomic fragments left after a large atomic nucleus undergoes nuclear fission. Typically, a large nucleus like that of uranium fissions by splitting into two smaller nuclei, along with a few neutrons, the release of heat energy, and gamma rays. The two smaller nuclei are the fission products..

<span class="mw-page-title-main">Scintigraphy</span> Diagnostic imaging test in nuclear medicine

Scintigraphy, also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally and the emitted gamma radiation is captured by gamma cameras, which are external detectors that form two-dimensional images in a process similar to the capture of x-ray images. In contrast, SPECT and positron emission tomography (PET) form 3-dimensional images and are therefore classified as separate techniques from scintigraphy, although they also use gamma cameras to detect internal radiation. Scintigraphy is unlike a diagnostic X-ray where external radiation is passed through the body to form an image.

<span class="mw-page-title-main">Potassium iodide</span> Ionic compound (KI)

Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are used. In the third world it is also used for treating skin sporotrichosis and phycomycosis. It is a supplement used by people with low dietary intake of iodine. It is administered orally.

Strontium-89 is a radioactive isotope of strontium produced by nuclear fission, with a half-life of 50.57 days. It undergoes β− decay into yttrium-89. Strontium-89 has an application in medicine.

<span class="mw-page-title-main">Iodine-131</span> Isotope of iodine

Iodine-131 is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuclear energy, medical diagnostic and treatment procedures, and natural gas production. It also plays a major role as a radioactive isotope present in nuclear fission products, and was a significant contributor to the health hazards from open-air atomic bomb testing in the 1950s, and from the Chernobyl disaster, as well as being a large fraction of the contamination hazard in the first weeks in the Fukushima nuclear crisis. This is because 131I is a major fission product of uranium and plutonium, comprising nearly 3% of the total products of fission. See fission product yield for a comparison with other radioactive fission products. 131I is also a major fission product of uranium-233, produced from thorium.

<span class="mw-page-title-main">Isotopes of iodine</span> Nuclides with atomic number of 53 but with different mass numbers

There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element.

Iodine-125 (125I) is a radioisotope of iodine which has uses in biological assays, nuclear medicine imaging and in radiation therapy as brachytherapy to treat a number of conditions, including prostate cancer, uveal melanomas, and brain tumors. It is the second longest-lived radioisotope of iodine, after iodine-129.

Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2230 hours; the decay by electron capture to tellurium-123 emits gamma radiation with a predominant energy of 159 keV. In medical applications, the radiation is detected by a gamma camera. The isotope is typically applied as iodide-123, the anionic form.

<span class="mw-page-title-main">Iobenguane</span> Chemical compound

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine (noradrenaline), typically used as a radiopharmaceutical. It acts as a blocking agent for adrenergic neurons. When radiolabeled, it can be used in nuclear medicinal diagnostic and therapy techniques as well as in neuroendocrine chemotherapy treatments.

Radium-223 is an isotope of radium with an 11.4-day half-life. It was discovered in 1905 by T. Godlewski, a Polish chemist from Kraków, and was historically known as actinium X (AcX). Radium-223 dichloride is an alpha particle-emitting radiotherapy drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover. The principal use of radium-223, as a radiopharmaceutical to treat metastatic cancers in bone, takes advantage of its chemical similarity to calcium, and the short range of the alpha radiation it emits.

<span class="mw-page-title-main">Bone metastasis</span> Medical condition

Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing sarcoma are rare; the most common bone tumor is a metastasis. Bone metastases can be classified as osteolytic, osteoblastic, or both. Unlike hematologic malignancies which originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases, especially in a state of advanced disease, can cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.

<span class="mw-page-title-main">Radioactive iodine uptake test</span> Diagnostic test for causes of hyperthyroidism

The radioactive iodine uptake test is a type of scan used in the diagnosis of thyroid problems, particularly hyperthyroidism. It is entirely different from radioactive iodine therapy, which uses much higher doses to destroy cancerous cells. The RAIU test is also used as a follow-up to RAI therapy to verify that no thyroid cells survived, which could still be cancerous.

The history of radiation therapy or radiotherapy can be traced back to experiments made soon after the discovery of X-rays (1895), when it was shown that exposure to radiation produced cutaneous burns. Influenced by electrotherapy and escharotics—the medical application of caustic substances—doctors began using radiation to treat growths and lesions produced by diseases such as lupus, basal cell carcinoma, and epithelioma. Radiation was generally believed to have bactericidal properties, so when radium was discovered, in addition to treatments similar to those used with x-rays, it was also used as an additive to medical treatments for diseases such as tuberculosis where there were resistant bacilli.

A medical isotope is an isotope used in medicine. The first uses of isotopes in medicine were in radiopharmaceuticals, and this is still the most common use. However more recently, separated stable isotopes have come into use.

Targeted alpha-particle therapy 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. It has the potential to provide highly targeted treatment, especially to microscopic tumour cells. Targets include leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis. 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.

<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Samuel M. Seidlin was Russian-born American endocrinologist who pioneered the field of nuclear medicine by using radioiodine for diagnosis and therapy of thyroid cancer during the early 1940s.

References

  1. ↑ Buscombe, J.; Navalkissoor, S. (1 August 2012). "Molecular radiotherapy". Clinical Medicine. 12 (4): 381–386. doi: 10.7861/clinmedicine.12-4-381 . PMC   4952132 . PMID   22930888.
  2. ↑ Volkert, Wynn A.; Hoffman, Timothy J. (1999). "Therapeutic Radiopharmaceuticals". Chemical Reviews. 99 (9): 2269–2292. doi:10.1021/cr9804386. PMID   11749482.
  3. ↑ Nicol, Alice; Waddington, Wendy (2011). Dosimetry for radionuclide therapy. York: Institute of Physics and Engineering in Medicine. ISBN   9781903613467.
  4. ↑ Martin, Elizabeth A; McFerran, Tanya A, eds. (2014). A dictionary of nursing (6th ed.). Oxford: Oxford University Press. doi:10.1093/acref/9780199666379.001.0001. ISBN   9780199666379.
  5. ↑ 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. (11 July 2012). "The SNMMI Practice Guideline for Therapy of Thyroid Disease with 131I 3.0". Journal of Nuclear Medicine. 53 (10): 1633–1651. doi: 10.2967/jnumed.112.105148 . PMID   22787108.
  7. ↑ IAEA (1996). Manual on therapeutic uses of iodine-131 (PDF). Vienna: International Atomic Energy Agency. p. 7.
  8. ↑ IAEA; ICRP (2009). Release of patients after radionuclide therapy. Vienna, Austria: International Atomic Energy Agency. ISBN   978-92-0-108909-0.
  9. ↑ Den, RB; Doyle, LA; Knudsen, KE (April 2014). "Practical guide to the use of radium 223 dichloride". The Canadian Journal of Urology. 21 (2 Supp 1): 70–6. PMID   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; Hartsell, William (March 2011). "Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline". International Journal of Radiation Oncology, Biology, Physics. 79 (4): 965–976. doi: 10.1016/j.ijrobp.2010.11.026 . PMID   21277118.
  11. ↑ Goyal, Jatinder; Antonarakis, Emmanuel S. (October 2012). "Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases". Cancer Letters. 323 (2): 135–146. doi:10.1016/j.canlet.2012.04.001. PMC   4124611 . PMID   22521546.
  12. ↑ Serafini, AN (15 June 2000). "Samarium Sm-153 lexidronam for the palliation of bone pain associated with metastases". Cancer. 88 (12 Suppl): 2934–9. doi:10.1002/1097-0142(20000615)88:12+<2934::AID-CNCR9>3.0.CO;2-S. PMID   10898337. S2CID   45863868.
  13. ↑ Tennvall, Jan; Brans, Boudewijn (30 March 2007). "EANM procedure guideline for 32P phosphate treatment of myeloproliferative diseases". European Journal of Nuclear Medicine and Molecular Imaging. 34 (8): 1324–1327. doi:10.1007/s00259-007-0407-4. PMID   17396258. S2CID   21759615.
  14. ↑ Raj, Gurdeep. Advanced Inorganic Chemistry Vol 1. Krishna Prakashan Media. p. 497. ISBN   9788187224037.
  15. ↑ Gropper, Sareen S.; Smith, Jack L. (2012-06-01). Advanced Nutrition and Human Metabolism. Cengage Learning. p. 432. ISBN   978-1133104056.
  16. ↑ Siegel, Michael E.; Siegel, Herrick J.; Luck, James V. (October 1997). "Radiosynovectomy's clinical applications and cost effectiveness: A review". Seminars in Nuclear Medicine. 27 (4): 364–371. doi:10.1016/S0001-2998(97)80009-8. PMID   9364646.
  17. ↑ Allen, Theresa M. (October 2002). "Ligand-targeted therapeutics in anticancer therapy". Nature Reviews Cancer. 2 (10): 750–763. doi:10.1038/nrc903. PMID   12360278. S2CID   21014917.
  18. ↑ Sharp, Susan E.; Trout, Andrew T.; Weiss, Brian D.; Gelfand, Michael J. (January 2016). "MIBG in Neuroblastoma Diagnostic Imaging and Therapy". RadioGraphics. 36 (1): 258–278. doi:10.1148/rg.2016150099. PMID   26761540.
  19. ↑ Maqsood, Muhammad Haisum; Tameez Ud Din, Asim; Khan, Ameer H (30 January 2019). "Neuroendocrine Tumor Therapy with Lutetium-177: A Literature Review". Cureus. 11 (1): e3986. doi: 10.7759/cureus.3986 . PMC   6443107 . PMID   30972265.
  20. ↑ Morgenstern, Alfred; Bruchertseifer, Frank; Apostolidis, Christos (1 June 2012). "Bismuth-213 and Actinium-225 – Generator Performance and Evolving Therapeutic Applications of Two Generator-Derived Alpha-Emitting Radioisotopes". Current Radiopharmaceuticals. 5 (3): 221–227. doi:10.2174/1874471011205030221. PMID   22642390.
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