Radionuclide therapy of bone metastases

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The radionuclide therapy of bone metastases is a nuclear medical process for the palliative treatment of bone metastases .

description

In radionuclide therapy of bone metastases , radiopharmaceuticals are injected into the patient . Radionuclides are currently (as of 2011) essentially only β-emitters , such as 89 Sr (as chloride ), 90 Y (as citrate ), 32 P (as sodium phosphate), samarium -153-EDTMP (ethylenediamine-tetra (methylenephosphonic acid); a phosphonate - analogue of ethylenediaminetetraacetic acid ) and rhenium -186-HEDP (hydroxy-ethylene diphosphonate) are used. These radiopharmaceuticals have a high affinity for bones , which means that they are built into the bones quickly and to a large extent after administration (application). Areas with high bone turnover, such as bone metastases, absorb these β-emitters to a greater extent. The tissue damage is therefore particularly high in the area of ​​the metastases. Depending on the range of the electron released during decay, a few millimeters of the surrounding healthy tissue are also damaged. Due to their chemical similarity to calcium, 89 strontium and 90 Y are incorporated directly into the bones as free ions. Also, 32 P as phosphate absorbed directly from the bone. In the case of the radionuclides 153 Sm and 186 Re , the bone affinity is achieved through the chemical bond to bisphosphonates with an affinity for bone. As with radiation therapy, radionuclide therapy inhibits bone remodeling and inflammation in the area of ​​the bone metastases. The effectiveness of radionuclide therapy for bone metastases in breast cancer and prostate cancer has been demonstrated in several studies . The response rate is around 70% of the treated patients. Complete freedom from pain is achieved in around 30% of patients. Pain relief begins about 48 hours after treatment with 186 Re and 153 Sm and lasts between one and twelve months. In the first two to four days, about 10 to 30% of patients experience an initial worsening of pain ( pain flare ) lasting an average of three days .

Iodine-131 ( radioiodine therapy ) can be used to treat bone metastases from thyroid carcinoma . The bone metastases can be detected beforehand with the help of the diagnostic radionuclide iodine-123 and the potential radioiodine uptake for the therapy can be checked. In contrast to most other tumors, the chances of a cure in thyroid cancer are relatively high, even after metastasis to the bones. The 5-year and 10-year survival rates in a study from 2001 were 41 and 15%, respectively.

The range of the β-radiation is - depending on the radionuclide used - in the range of several millimeters. This can affect the healthy bone marrow surrounding the bone metastases. The myelotoxicity , meaning the damage blood cell-forming stem cells of the bone marrow limited both the applicable activity and the number of treatment cycles. The normal activity of radionuclides for the treatment of bone metastases reduces the function of blood formation in the red bone marrow to about a third of the initial values. This effect subsides after about two months. Patients with anemia or leukopenia are therefore usually excluded from radionuclide therapy.

The radiobiological effectiveness ( radio biological effectiveness , RBE) of the β-radiation is relatively low. In contrast to this, α emitters have a significantly higher energy input and thus a significantly higher radiobiological effectiveness. In this context, one speaks of a high linear energy transfer ( high LET , high linear energy transfer ). β emitters have a low linear energy transfer ( low LET ). The low-LET only occasionally leads to strand breaks in the DNA of the tumor cells, while the high-LET triggers irreparable double-strand breaks in the DNA. The cell's repair mechanisms are largely overwhelmed by the effects of α emitters. The dose-effect relationship is almost linear with high-LET radiation sources, while it is linear-quadratic with low-LET radiation sources. Another advantage is the short range of the α-particles in the body tissue of less than 100 µm. The dependence of the effectiveness of a radionuclide therapy on the cell cycle (G 0 ) is significantly less than with the β-emitters due to the severe damage that α-radiation causes in the cells.

With 223 Ra -chloride (Alpharadin, trade name Xofigo) an α-emitter is approved for the treatment of symptomatic bone metastases of castration-resistant prostate carcinomas. The 223 Ra is also intended to damage the bone metastases in a targeted manner and - due to the very short range of the α radiation - largely protect the surrounding tissue. In Phase II clinical trials, the median survival time of patients receiving radium-223 was 65.3 weeks, while it was 46.4 weeks for patients receiving placebo . Because of its similarity to calcium, the body prefers to build radium into the bones. Bone-building metastases enrich the radium to a greater extent because of their high mineral requirements.

Individual evidence

  1. ^ RG Robinson, DF Preston, M. Schiefelbein, KG Baxter: Strontium 89 therapy for the palliation of pain due to osseous metastases. In: JAMA Volume 274, Number 5, August 1995, pp. 420-424, ISSN  0098-7484 . PMID 7542352 . (Review).
  2. ↑ SK Shukla, GS Limouris, R. Cusumano, A. Acconcia, C. Cipriani, G. Atzei, G. Argirò, S. Boemi: Advanced prostate cancer diagnosis and therapy with gallium-67 and yttrium-90, respectively. In: Anticancer Research Volume 17, Number 3B, 1997 May-Jun, pp. 1731-1734, ISSN  0250-7005 . PMID 9179226 .
  3. ↑ a b E. B. Silberstein: Teletherapy and radiopharmaceutical therapy of painful bone metastases. In: Seminars in nuclear medicine Volume 35, Number 2, April 2005, pp. 152-158, ISSN  0001-2998 . doi : 10.1053 / j.semnuclmed.2004.11.006 . PMID 15765378 . (Review).
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  5. ↑ Palliative pain therapy for skeletal metastases. ( Memento of the original from May 30, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Ulm University Hospital, accessed on February 25, 2011 @1@ 2Template: Webachiv / IABot / www.uniklinik-ulm.de
  6. ^ A b D. A. Loblaw, JS Wu, P. Kirkbride, T. Panzarella, K. Smith, J. Aslanidis, P. Warde: Pain flare in patients with bone metastases after palliative radiotherapy - a nested randomized control trial. In: Supportive care in cancer Volume 15, Number 4, April 2007, pp. 451-455, ISSN  0941-4355 . doi : 10.1007 / s00520-006-0166-y . PMID 17093912 .
  7. ↑ JC Sisson, YK Dewaraja, EJ Wizauer, TJ Giordano, AM Avram: Thyroid carcinoma metastasis to skull with infringement of brain: treatment with radioiodine. In: Thyroid Volume 19, Number 3, March 2009, pp. 297-303, ISSN  1557-9077 . doi : 10.1089 / thy.2008.0426 . PMID 19207003 . PMC 2727798 (free full text).
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  11. ↑ TO Serafini: Current status of systemic intravenous radiopharmaceuticals for the treatment of painful metastatic bone disease. In: International journal of radiation oncology, biology, physics Volume 30, Number 5, December 1994, pp. 1187-1194, ISSN  0360-3016 . PMID 7525518 . (Review).
  12. ^ P. Koehler: Radiation therapy of bone metastases. ( Memento of the original from March 31, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 606 kB) In: radiologen-konstanz.de 4, 2005 @1@ 2Template: Webachiv / IABot / www.radiologen-konstanz.de
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  15. ↑ W. Hiddemann, CR Bartram: Die Onkologie. Verlag Springer, 2009, ISBN 3-540-79724-6 , p. 246. ISBN limited preview in the Google book search
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  17. ^ A b S. Nilsson, RH Larsen, SD Fosså, L. Balteskard, KW Borch, JE Westlin, G. Salberg, OS Bruland: First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. In: Clinical Cancer Research Volume 11, Number 12, June 2005, pp. 4451-4459, ISSN  1078-0432 . doi : 10.1158 / 1078-0432.CCR-04-2244 . PMID 15958630 .
  18. ↑ European Medicines Agency : Xofigo. Radium-223 dichloride (PDF; 75 kB). EMA / 579264/2013, EMEA / H / C / 002653, November 13, 2013.
  19. ↑ Bayer and Algeta are jointly developing treatments for cancer patients with bone metastases.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. Bayer Schering Pharma press release dated September 3, 2009@1@ 2Template: Dead Link / viva.vita.bayerhealthcare.com  
  20. ↑ clinicaltrials.gov: A Phase III Study of Alpharadin (Radium-223) in Patients With Symptomatic Hormone Refractory Prostate Cancer With Skeletal Metastases (ALSYMPCA). As of January 6, 2011, accessed February 25, 2011
  21. ↑ S. Nilsson, L. Franzén, C. Parker, C. Tyrrell, R. Blom, J. Tennvall, B. Lennernäs, U. Petersson, DC Johannessen, M. Sokal, K. Pigott, J. Yachnin, M. Garkavij, P. Strang, J. Harmenberg, B. Bolstad, OS Bruland: Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomized, multicentre, placebo-controlled phase II study. In: The Lancet Oncology Volume 8, Number 7, July 2007, pp. 587-594, ISSN  1470-2045 . doi : 10.1016 / S1470-2045 (07) 70147-X . PMID 17544845 .
  22. ^ RL Carter: Patterns and mechanisms of bone metastases. In: Journal of the Royal Society of Medicine Volume 78 Suppl 9, 1985, pp. 2-6, ISSN  0141-0768 . PMID 4045915 . PMC 1289525 (free full text).
  23. ↑ Shelley MD, Mason MD: Radium-223 for men with hormone-refractory prostate cancer and bone metastases. In: The lancet oncology Volume 8, Number 7, July 2007, pp. 564-565, ISSN  1470-2045 . doi : 10.1016 / S1470-2045 (07) 70180-8 . PMID 17613416 .
  24. ↑ Ø. Bruland, S. Nilsson, DR Fisher, RH Larsen: High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? In: Clinical cancer research Volume 12, Number 20 Pt 2, October 2006, pp. 6250s-6257s, ISSN  1078-0432 . doi : 10.1158 / 1078-0432.CCR-06-0841 . PMID 17062709 .