European Nuclear Medicine Guide
Radiopharmaceutical: Strontium-89 chloride ([89Sr]SrCl2).
Nuclide: Strontium-89 emits a β particle with a maximum energy of 1.46 MeV, mean energy of 0.58 MeV, average soft tissue range of 2.4 mm, and 0.01% abundant γ emission with a 0.91 MeV photo peak. The physical half-life is 50.5 days.
Activity: 150 MBq (1.5-2.2 MBq/kg).
Administration: Strontium-89 is available as [89Sr]SrCl2 in a sterile water solution for intravenous (i.v.) administration.
Strontium-89, a group II metal, is taken up like calcium in osteoblastic skeletal metastases [54]. Approximately 85% of the Strontium-89 is ultimately excreted into the urine with a renal plasma clearance of approximately 1.5 to 11.5 L/day. Less than 10% is excreted on the first day. This rate of excretion is usually lower in patients with skeletal metastases. The total body retention after three months varies between 11% and 88% depending on the extent of metastasis.
Patients should meet the following conditions:
Relative Contraindications:
In general, there is an increased risk of haematological adverse reactions such as neutropenia and thrombocytopenia in patients with evidence of compromised bone marrow reserve, e.g. following prior cytotoxic chemotherapy and/or radiation treatment (such as extensive external beam radiation therapy, EBRT) or in patients with advanced diffuse metastatic infiltration of the bone. These patients should be treated only after careful clinical risk-benefit assessment. Close monitoring is necessary. Usually a superscan appearance on the bone scan corresponds to a major site of bone marrow involvement and is a contraindication because of possible side effects. Moreover, therapy with bone-seeking radiopharmaceuticals cannot be recommended in this situation, since valid data on overall efficacy are not available.
A relatively low blood cell count, within certain limits, may be a relative contraindication to radionuclide bone treatment because of possible myelotoxicity. Nevertheless, the precise lower limit is not well defined in the literature and the use of granulocyte colony-stimulating factors may further lower the limit.
The following cell count limits should be applied:
The presence of bone marrow involvement does not represent a contraindication provided that blood values remain within the cited limits and the extent of substitution does not exceed a threshold above which severe myelotoxicity is expected.
Blood cell counts should be stable before undertaking bone palliation therapy. If there is any doubt or delay in performing the therapy due to low blood cell counts, it might be worthwhile repeating blood sampling just before the treatment to exclude rapid deterioration in blood cell counts before administration of the therapeutic radionuclides.
The facilities required will depend on the national legislation for the emission of β-γ emitting therapy agents.
According to EANM guidelines published in 2008, there is no evidence of competition between bisphosphonates and bone seeking radionuclides including [89Sr]SrCl2 Therefore, they may be used Concomitantly [53]. Calcium therapy should be preferably discontinued for at least two weeks prior to treatment.
[89Sr]SrCl2 should be slowly administered intravenously, through a drip or butterfly needle and three-way tap, over a period of four minutes and subsequently flushed with saline. The syringe containing [89Sr]SrCl2 should be protected with a Perspex syringe shield. The product can be administered on an out-patient basis, and there are no restrictions on normal interactions with friends or relations.
The radiopharmaceutical is excreted mainly into the urine and the toilet to be used should therefore be connected to sewage, and not a septic tank.
Haematological values should be checked every two weeks following therapy to determine whether the thrombocyte levels have returned to normal (after approximately 8 weeks). The first outpatient follow-up appointment should be scheduled for three weeks after treatment. In the event of a significant reduction in thrombocytes, the patient should return for weekly follow-up appointments until the thrombocyte level has returned to normal. Follow-up nuclear medicine appointments should be scheduled in close collaboration with the patient’s lead specialist. The patient should be instructed to use adequate contraception for the four months following treatment. Incontinent patients should be given sufficient incontinence materials to last five days. It is important to note that patients excrete significant amounts of Strontium-89 in the urine for a significant period of time following the treatment.
Operating theatres and pathology laboratories are usually not required to take any additional radiation safety measures (other than normal radiation safety procedures) when working with patients who require surgery within two weeks of receiving [89Sr]SrCl2 therapy, but it may vary according to national legislations.
Death of the patient following administration of Strontium-89: Cremation of the patient is usually not prohibited although scattering of the ashes over land may not permitted, depending on national legislation.
The radiation dose to individual bone metastases is between 9-92 Gy depending on the size of the lesion with a median of 68 cGy/MBq [54,56].
Absorbed doses per administered activity of Strontium-89 are: for bone surface 17.0 mGy/MBq, for red bone marrow 11.0 mGy/MBq, for lower bowel wall 4.7 mGy/MBq, for bladder wall 1.3 mGy/MBq, for testes 0.8 mGy/MBq, for ovaries 0.8 mGy/MBq, for uterine wall 0.8 mGy/MBq, and kidneys 0.8 mGy/MBq [57].
The effectiveness of Strontium-89 is comparable to that of external radiotherapy. External radiotherapy (or neurosurgery) is always preferable in patients with myelocompression or threatened/current neurological deficit. Extensive neurological examination should be a standard part of the analysis of patients with painful skeletal metastases. Previous external radiotherapy confined to a limited area is not a contraindication for treatment using Strontium-89.
Patients with prostate cancer are often suitable for chemotherapy. Due to its long physical half-life, Strontium-89 is not recommended in patients receiving (myelotoxic) chemotherapy. Therefore, the use of [89Sr]SrCl2 for bone metastasis of prostate cancer is nowadays limited. Short-lived radiopharmaceuticals such as [188Re]Re-HEDP and [153Sm]Sm-EDTMP are preferred. In contrast to [188Re]Re-HEDP and [153Sm]Sm-EDTMP, [89Sr]SrCl2 is not indicated for patients with bone metastases from primaries other than prostate cancer.
During the first 48 h following administration of the Strontium-89, a small number of patients might experience an increase in pain (known as the ‘flare phenomenon’) which recedes spontaneously and is generally followed by a good response to the Strontium-89 therapy.
The thrombocyte count is the most sensitive parameter with regard to bone marrow toxicity. Thrombocytopenia with a decrease of approximately 70% from baseline blood counts could occur and usually reaches its lowest point after 4-6 weeks; recovery is seen within 3-6 months. Severe thrombocytopenia is rare and could occur in patients with known bone marrow deficiency, for example, as a result of chemotherapy. Bone marrow toxicity also increases with repeated [89Sr]SrCl2 treatments.
Strontium-89 is approved in some European countries for pain reduction as supportive care for symptomatic bone metastases from prostate cancer [53].