β-emitter bone-pain palliation

Indications

• Painful bone metastases with an osteoblastic or mixed pattern, confirmed by intense uptake at the painful sites on a bone scan within 8 weeks (EANM 2018, grade A).
• Multifocal pain when analgesia and local radiotherapy are inadequate, or as an adjunct to local radiotherapy.
• Labels: Metastron (EU) for prostate cancer bone pain after hormone therapy failure, as an adjunct or alternative to radiotherapy. Sr-89 (US) for bone pain from skeletal metastases. Quadramet (EU) for multiple painful osteoblastic metastases that take up ⁹⁹ᵐTc-bisphosphonate.
• Breast cancer and other osteoblastic primaries are treated too, but the evidence is weaker (EANM: level 4 for breast cancer).
• mCRPC with bone-only disease: consider ²²³Ra first, because it is the only bone-seeking radionuclide with a survival benefit (EANM 2018).
• ¹⁸⁶Re-HEDP and generator-produced ¹⁸⁸Re-HEDP are used where available; availability of all these agents varies by country.

Contraindications

• Absolute: pregnancy and breastfeeding (EANM).
• Superscan on the bone scan (diffuse marrow involvement; high toxicity risk, no efficacy data).
• Marrow failure, or counts below the limits (EANM: Hb <90 g/L, WBC <3.5 ×10⁹/L, platelets <100 ×10⁹/L). Subclinical DIC raises the risk of severe thrombocytopenia.
• Severe renal impairment: creatinine >180 µmol/L and/or GFR <30 mL/min.
• Life expectancy under 4 weeks.
• Not a primary treatment for spinal cord compression or impending pathological fracture; use radiotherapy or surgery.
• Bone scan negative at the painful site: use external beam radiotherapy instead.
• ¹⁵³Sm-EDTMP (EU SmPC): hypersensitivity to phosphonates; chemotherapy or hemibody radiotherapy in the previous 6 weeks; concurrent myelotoxic chemotherapy.

• Blood-count thresholds differ by source. EANM (grade C): do not treat if Hb <90 g/L, WBC <3.5 ×10⁹/L or platelets <100 ×10⁹/L. Metastron SmPC: WBC >3.0 ×10⁹/L, platelets >100 ×10⁹/L, Hb >90 g/L. Quadramet SmPC: consider not treating if Hb <100 g/L, WBC <5, ANC <2 or platelets <100 ×10⁹/L. US Sr-89 PI: caution if platelets <60 or WBC <2.4 ×10⁹/L.
• Choice of agent (EANM): short-lived agents such as ¹⁵³Sm give quicker relief and suit progressive disease with pain; long-lived ⁸⁹Sr gives longer responses but more prolonged myelosuppression. No clear difference in response rate has been shown.
• Onset of relief: within 1 week for ¹⁵³Sm (SmPC); typically 7–20 days for ⁸⁹Sr (US PI).
• ¹⁸⁸Re-HEDP dose escalation used 1.3–4.4 GBq; 4.4 GBq may be tolerable when platelets are well above 200 ×10⁹/L. For ¹⁸⁶Re-HEDP in breast cancer, the maximum tolerated activity was 2405 MBq.
• Effective dose: 465 mSv for 150 MBq ⁸⁹Sr (Metastron SmPC); 798 mSv for 2600 MBq ¹⁵³Sm-EDTMP (Quadramet SmPC).

• Myelosuppression is the main toxicity: thrombocytopenia and leucopenia. Grade 3–4 toxicity depends on prior myelosuppressive therapy and marrow reserve. Recovery is usually complete or partial within 3 months (EANM).
• Nadir by agent: ¹⁵³Sm 3–5 weeks, with recovery by about 8 weeks; ⁸⁹Sr 12–16 weeks, with slow recovery; rhenium-HEDP weeks 2–5.
• Pain flare in about 10%, usually within 72 h (36–72 h for ⁸⁹Sr): mild and self-limiting, treated with analgesics, and often a sign of response.
• Spinal cord compression may follow when there are cervicodorsal spinal metastases; image first and consider prophylactic steroids.
• Calcium-like flushing if ⁸⁹Sr is injected in under 30 s.
• Rare serious events after ¹⁵³Sm: DIC, bone marrow failure, intracranial haemorrhage with thrombocytopenia, and hypersensitivity (Quadramet SmPC).
• Hold further bone-seeker or myelosuppressive treatment until counts recover; withhold myelosuppressive systemic therapy for about 12 weeks afterwards.

• Follow national release rules. Where outpatient treatment is allowed, EANM advises keeping the patient in the department for 4–6 h after injection; where national law requires admission, use a shielded room with an en-suite toilet.
• Excretion is mainly urinary, highest in the first 2–3 days. ¹⁵³Sm urinary excretion is nearly complete by 8–12 h (35% of activity by 12 h). ⁸⁹Sr is excreted about two-thirds in urine and one-third in faeces.
• Hygiene advice (EANM): avoid soiling clothes or the area around the toilet for 1 week after ⁸⁹Sr or 2–3 days after ¹⁵³Sm; double flush; wash hands; wash heavily soiled clothes separately.
• Incontinence: catheterise before injection and keep the catheter for 4 days (⁸⁹Sr) or 24 h (¹⁵³Sm); carers wear gloves and empty bags often.
• ¹⁵³Sm: limit close contact with infants and pregnant women for 48 h (Quadramet SmPC).
• Avoid pregnancy for at least 6 months after ⁸⁹Sr or ¹⁵³Sm (EANM). Stop breastfeeding before ⁸⁹Sr (US PI).
• Staff: shield the vial (⁸⁹Sr bremsstrahlung adds to the contact dose); treat unused product and administration sets as radioactive waste. A medical emergency takes priority over radiation precautions.