Radiophosphorus therapy

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The radiophosphorus therapy is a radionuclide in vera Polycythemia and essential thrombocythemia . The radionuclide 32 phosphorus is used. The method is considered an alternative to conventional treatment methods - due to its side effect profile, however, it is mainly used in older patients over 65 or 70 years of age.

Areas of application and alternatives

The most common indication for radiophosphorus therapy is polycythemia vera (PV), which is one of the myeloproliferative diseases . Another indication is essential thrombocythemia (ET).

Pregnancy and breastfeeding are considered absolute contraindications for treatment with 32 P, and women of childbearing age are considered relative contraindications . Due to the age distribution of the disease, these contraindications rarely occur in practice. Other relative contraindications are a rapid deterioration in kidney function , a very low number of white blood cells ( leukocytopenia ) or - in the case of ET - a very low hemoglobin level ( anemia , anemia ).

The therapy of choice for polycythemia vera is initially bloodletting . Since there is a risk of osteomyelofibrosis with bloodletting therapy alone , additional therapies with hydroxycarbamide or busulfan are usually carried out .

Therapy principle and physical basics

Dihydrogen phosphate ion

The radioactive phosphorus isotope 32 phosphorus ( 32 P) used is produced in nuclear reactors and is available for therapy as dihydrogen phosphate or as sodium phosphate in liquid form. The radionuclide is - after clarification and consent of the patient - strictly intravenously through a peripheral venous catheter administered (applied). To reduce the radiation dose of the punctured vessel, the punctured vein should then be flushed with isotonic saline solution . Oral administration can also be used as an alternative .

The specified activities are 3.7  MBq per kilogram of body weight or 80 to 110 MBq per m 2 of body surface . The maximum activity of a single treatment is given as 185 to 260 MBq. Some authors call for an activity reduction of 25% for patients over 80 years of age.

32 P is absorbed into the pool of inorganic phosphorus and 20% is excreted with the urine within 24 hours. For reasons of radiation protection , it is therefore recommended to carry out the therapy in a facility that is connected to a decay system or to collect the urine and only dispose of it when the radioactivity has subsided. The remaining 80% is absorbed into various organic and inorganic phosphorus compounds in the human body. For example, phosphorus is incorporated directly into nucleic acids and therefore accumulates in tissues with high cell proliferation , to which the bone marrow belongs as the site of blood formation . If, due to the disease, there is also blood formation outside the bone marrow (extramedullary blood formation), the radiopharmaceutical will also accumulate there. 32 Phosphorus is also absorbed into the calcium phosphate of the bone and from there contributes to the radiation dose to the bone marrow.

32 P is a pure beta emitter with a maximum energy of 1.71  MeV , an average energy of 0.70 MeV, a maximum range in tissue of 7.9  mm , an average range of 3 mm and a physical half-life of 14.3 Days. The biological half-life in the bone marrow is about 7 to 9 days. The highest doses of radiation arise in the bone marrow, liver and spleen .

The radiation from the 32 P causes damage to the DNA in the immediate vicinity , in particular double strand breaks, which ultimately lead to the initiation of programmed cell death ( apoptosis ) (→  mechanism of action of radiation therapy ). This antiproliferative effect includes the cell lines that are affected in polycythemia vera. The result is an inhibition of the hyperproliferative cell lines, not an extinction.

The therapeutic goals of polycythemia vera are normalization of the total volume of all erythrocytes , a reduction in the number of platelets below 500,000 / µl and a decrease in splenomegaly . If the goals are not achieved with the first treatment, the radiophosphorus therapy can be repeated after 4 months with a quarter increase in activity . The total dose should not exceed 600 MBq per year.

Risks and Side Effects

If the injection of the radiopharmaceutical does not get into the vein but into the tissue around the vein ( extravasation ), the tissue there can die ( radionecrosis ).

Relative leukocytopenia (decrease in the number of white blood cells) and thrombocytopenia (decrease in the number of blood platelets) usually develop within four to six weeks, and regress within four months.

Approximately 10% (2 to 15%) of patients treated with 32 P develop acute myeloid leukemia within 10 years of treatment . The frequency seems to depend on the activity involved. According to other sources, there is no significant association between total activity administered and the rate of leukemia. However, roughly the same frequencies for the development of leukemia also apply to patients who were treated with hydroxycarbamide or busulfan .

Another complication described, which can also occur with other forms of therapy, is osteomyelofibrosis .

successes

98% of patients - according to other sources only 60 to 90% - achieve a complete remission within three to four months , which lasts for a median of three years. After 14 years of maintenance therapy with low-dose hydroxycarbamide , 60% of the patients still had a complete remission. Radiophosphorus therapy is therefore considered "a well-tolerated and efficient therapy for older patients with polycythemia vera, which leads to a long mean survival time with excellent quality of life".

history

The first radionuclide therapy with 32 P for polycythemia vera was described by Lawrence in 1953. The method had previously been used for leukemia .

Literature and Sources

Individual evidence
  1. ↑ a b c d e f Jan Tennvall, Boudewijn Brans. EANM procedure guideline for 32 P phosphate treatment of myeloproliferative diseases. (PDF, 101 kB) Eur J Nucl Med Mol Imaging (2007) 34: 1324-1327. doi : 10.1007 / s00259-007-0407-4 Guideline (2007) of the European Association of Nuclear Medicine (EANM).
  2. ↑ Najean Y, Rain JD, Goguel A., et al. : [Treatment of polycythemia. I - Using radiophosphorus with or without treatment in 483 patients over 65 years of age] . In: Ann Med Interne (Paris) . 149, No. 2, March 1998, pp. 87-93. PMID 11490530 .
  3. ^ A b c Hans-Joachim Hermann: Nuclear medicine . Elsevier, Urban and Fischer, Munich 2004, ISBN 3-437-47550-9 ( limited preview in Google book search).
  4. ↑ Najean Y, Rain JD: Treatment of polycythemia vera: use of 32P alone or in combination with maintenance therapy using hydroxyurea in 461 patients greater than 65 years of age. The French Polycythemia Study Group . In: Blood . 89, No. 7, April 1997, pp. 2319-27. PMID 9116275 .
  5. ^ Freimut DE youth, Thomas Krause. Special nuclear medicine therapies. in: Torsten Kuwert, Frank Grünwald , Uwe Haberkorn , Thomas Krause (Eds.) Nuclear Medicine. Stuttgart 2008 ISBN 978-3-13-118504-4 p. 457
  6. ^ JH Lawrence, HI Berlin, RL Huff: The nature and treatment of polycythemia; studies on 263 patients . In: Medicine (Baltimore) . 32, No. 3, September 1953, pp. 323-88. PMID 13086142 .