Initially intermittent pain of variable intensity; progresses to chronic pain with breakthrough acute episodes
Major impact on quality of life
Mechanical allodynia (normal, nonpainful activities become painful, e.g., coughing)
Metastatic bone tumor therapy
Radiopharmaceutical treatment of metastatic bone pain refractory to analgesics
Alpha emitter: Ra-223 (trade name Xofigo; formerly known as Alpharadin)
ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial showed survival benefit of Ra-223 treatment in castration-resistant prostate cancer (CRPC) patients
Median survival advantage of 3.6 months as compared to placebo
30% ↓ in risk of death compared to placebo
Monthly IV administration of Ra-223 for 6 months
Usually effective by 3rd Ra-223 administration (3 months)
Approved for prostate cancer
Beta emitters: Sm-153, Sr-89
Considered palliative to reduce pain
One-time IV therapy, but can be repeated
Usually effective within 1-2 weeks after administration
Approved for multiple tumors that metastasize to bone
Alpha Emitter
Ra-223
1st α-particle therapy approved in United States
1st radiopharmaceutical therapy that extends survival in patients with bone metastases
Bone-seeking α emitter mimicking calcium, 4 α-particles generated for each decay
Produced from Ra-223 extraction generator (parent isotopes Ac-227 and Th-227)
t1/2: 11.43 days
Alpha emission (95.3%; energy range: 5-7.5 MeV), beta emission (3.6%; average energies: 0.445 MeV and 0.492 MeV), gamma emission (1.1%; energy range: 0.01-1.27 MeV)
Greater biologic effectiveness due to high linear energy transfer
Less hematologic toxicity due to shorter path length (60-100 µm) of α-particles
Rapid blood clearance (< 1% blood activity at 24 hours), no significant redistribution
Decreases bone specific alkaline phosphatase (ALP), marker for tumor response in CRPC
Excretion: Gastrointestinal (52% activity in bowel at 24 hours), minimal urinary excretion (< 5%)
Mechanism of action
Increased uptake and complex formation with hydroxyapatite at sites of increased bone turnover
α-particle-induced double-stranded DNA breaks
Benefits
Survival benefit in symptomatic and progressive metastatic CRPC (≥ 2 skeletal metastases, no visceral metastases) regardless of disease extent, previous treatment with docetaxel and current treatment with bisphosphonates (ALSYMPCA trial)
16% of patients showed ≥ 30% drop in PSA at 12 weeks
Delayed onset of first symptomatic skeletal event (symptomatic pathologic bone fracture)
Pain relief
Improved quality of life
Delayed increase in ALP and PSA
Beta Emitters
Sm-153 (Lexidronam/Quadramet)
t1/2: 1.9 days
Dose: 1 mCi (37 MBq)/kg maximum
Mixed beta and gamma emitter
640, 710, and 810 keV beta emissions (mean: 0.23 MeV); average path length: 0.6 mm
Can image 103 keV gamma emissions (28% abundance)
Labeled to bisphosphonate ethylenediamine tetramethylene phosphate (EDTMP) (↑ bone-seeking properties)
Urinary excretion: Complete ~ 6 hours after administration
< 1% activity in blood 5 hours after injection
Sr-89 (Metastron)
t1/2: 50.5 days
Dose 40-60 uCi (1-1.6 MBq)/kg up to 4 mCi (148 MBq); dose can be repeated after 3-4 months
Pure beta emitter (1.49 MeV maximum energy; mean: 0.58 MeV), maximum path length: 8 mm; average path length: 2.4 mm
Bremsstrahlung imaging possible, but not practical
Used in patients with moderate pain, reasonable life expectancy (> 3 months) due to long response duration
P-32
First tracer used for metastatic bone pain palliation
Not widely used for bone pain palliation since 1980s; now abandoned
t1/2: 14.3 days
Pure beta emitter
Bremsstrahlung imaging possible, but not practical
Major drawback: Normal marrow receives high radiation dose relative to metastatic deposits (→ myelosuppression)
Also used to treat hematologic disease, primarily polycythemia vera
Rhenium 186 (Re-186)
t1/2: 90 hours
Not approved in United States
Similar to technetium, labeled to bisphosphonate
Gamma emission (187 keV) suitable for imaging
High radiation dose to normal bone
Tin 117m (Sn-117m), lutetium 177 (Lu-177)
Primarily investigational
Not currently in clinical use
Mechanism of action
Not well understood
Localized radiation to metastatic sites
May ↓ tumor volume
Likely ↓ in circulating cytokine, humoral factors that sensitize and stimulate nerve endings
PREPROCEDURE
Indications
Contraindications
Getting Started
PROCEDURE
Procedure Steps
Alternative Procedures/Therapies
POST PROCEDURE
Expected Outcome
OUTCOMES
Problems
Complications
Selected References
Den RB et al: Ra-223 treatment for bone metastases in castrate-resistant prostate cancer: Practical management issues for patient selection. Am J Clin Oncol. 42(4):399-406, 2019
Abi-Ghanem AS et al: Radionuclide therapy for osseous metastases in prostate cancer. Semin Nucl Med. 45(1):66-80, 2015
Shore ND: Radium-223 dichloride for metastatic castration-resistant prostate cancer: The urologist's perspective. Urology. 85(4):717-24, 2015
Pandit-Taskar N et al: Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride. J Nucl Med. 55(2):268-74, 2014
Wadas TJ et al: Molecular targeted α-particle therapy for oncologic applications. AJR Am J Roentgenol. 203(2):253-60, 2014
Wieder HA et al: Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters. World J Radiol. 6(7):480-5, 2014
Parker C et al: Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 369(3):213-23, 2013
Chiacchio S et al: Radionuclide therapy and integrated protocols for bone metastases. Q J Nucl Med Mol Imaging. 55(4):431-47, 2011
Bauman G et al: Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review. Radiother Oncol. 75(3):258-70, 2005
Damerla V et al: Recent developments in nuclear medicine in the management of bone metastases: a review and perspective. Am J Clin Oncol. 28(5):513-20, 2005
Liepe K et al: Systemic radionuclide therapy in pain palliation. Am J Hosp Palliat Care. 22(6):457-64, 2005
Liepe K et al: The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain. J Cancer Res Clin Oncol. 131(1):60-6, 2005
Pinski J et al: Prostate cancer metastases to bone: pathophysiology, pain management, and the promise of targeted therapy. Eur J Cancer. 41(6):932-40, 2005
Reisfield GM et al: Radiopharmaceuticals for the palliation of painful bone metastases. Am J Hosp Palliat Care. 22(1):41-6, 2005
Lam MG et al: 186Re-HEDP for metastatic bone pain in breast cancer patients. Eur J Nucl Med Mol Imaging. 31 Suppl 1:S162-70, 2004
Maini CL et al: 153Sm-EDTMP for bone pain palliation in skeletal metastases. Eur J Nucl Med Mol Imaging. 31 Suppl 1:S171-8, 2004
Pandit-Taskar N et al: Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 45(8):1358-65, 2004
Sapienza MT et al: Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy. Rev Hosp Clin Fac Med Sao Paulo. 59(6):321-8, 2004
Sartor O et al: Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 63(5):940-5, 2004
Ashayeri E et al: Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience. J Natl Med Assoc. 94(8):706-11, 2002
Lewington VJ: A practical guide to targeted therapy for bone pain palliation. Nucl Med Commun. 23(9):833-6, 2002
Giammarile F et al: Bone pain palliation with strontium-89 in cancer patients with bone metastases. Q J Nucl Med. 45(1):78-83, 2001
Hamdy NA et al: The palliative management of skeletal metastases in prostate cancer: use of bone-seeking radionuclides and bisphosphonates. Semin Nucl Med. 31(1):62-8, 2001
Han SH et al: 186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases. Q J Nucl Med. 45(1):84-90, 2001
Related Anatomy
Loading...
Related Differential Diagnoses
Loading...
References
Tables
Tables
KEY FACTS
Terminology
Preprocedure
Procedure
Post Procedure
TERMINOLOGY
Definitions
Bone pain is cardinal symptom of bone metastases
Initially intermittent pain of variable intensity; progresses to chronic pain with breakthrough acute episodes
Major impact on quality of life
Mechanical allodynia (normal, nonpainful activities become painful, e.g., coughing)
Metastatic bone tumor therapy
Radiopharmaceutical treatment of metastatic bone pain refractory to analgesics
Alpha emitter: Ra-223 (trade name Xofigo; formerly known as Alpharadin)
ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial showed survival benefit of Ra-223 treatment in castration-resistant prostate cancer (CRPC) patients
Median survival advantage of 3.6 months as compared to placebo
30% ↓ in risk of death compared to placebo
Monthly IV administration of Ra-223 for 6 months
Usually effective by 3rd Ra-223 administration (3 months)
Approved for prostate cancer
Beta emitters: Sm-153, Sr-89
Considered palliative to reduce pain
One-time IV therapy, but can be repeated
Usually effective within 1-2 weeks after administration
Approved for multiple tumors that metastasize to bone
Alpha Emitter
Ra-223
1st α-particle therapy approved in United States
1st radiopharmaceutical therapy that extends survival in patients with bone metastases
Bone-seeking α emitter mimicking calcium, 4 α-particles generated for each decay
Produced from Ra-223 extraction generator (parent isotopes Ac-227 and Th-227)
t1/2: 11.43 days
Alpha emission (95.3%; energy range: 5-7.5 MeV), beta emission (3.6%; average energies: 0.445 MeV and 0.492 MeV), gamma emission (1.1%; energy range: 0.01-1.27 MeV)
Greater biologic effectiveness due to high linear energy transfer
Less hematologic toxicity due to shorter path length (60-100 µm) of α-particles
Rapid blood clearance (< 1% blood activity at 24 hours), no significant redistribution
Decreases bone specific alkaline phosphatase (ALP), marker for tumor response in CRPC
Excretion: Gastrointestinal (52% activity in bowel at 24 hours), minimal urinary excretion (< 5%)
Mechanism of action
Increased uptake and complex formation with hydroxyapatite at sites of increased bone turnover
α-particle-induced double-stranded DNA breaks
Benefits
Survival benefit in symptomatic and progressive metastatic CRPC (≥ 2 skeletal metastases, no visceral metastases) regardless of disease extent, previous treatment with docetaxel and current treatment with bisphosphonates (ALSYMPCA trial)
16% of patients showed ≥ 30% drop in PSA at 12 weeks
Delayed onset of first symptomatic skeletal event (symptomatic pathologic bone fracture)
Pain relief
Improved quality of life
Delayed increase in ALP and PSA
Beta Emitters
Sm-153 (Lexidronam/Quadramet)
t1/2: 1.9 days
Dose: 1 mCi (37 MBq)/kg maximum
Mixed beta and gamma emitter
640, 710, and 810 keV beta emissions (mean: 0.23 MeV); average path length: 0.6 mm
Can image 103 keV gamma emissions (28% abundance)
Labeled to bisphosphonate ethylenediamine tetramethylene phosphate (EDTMP) (↑ bone-seeking properties)
Urinary excretion: Complete ~ 6 hours after administration
< 1% activity in blood 5 hours after injection
Sr-89 (Metastron)
t1/2: 50.5 days
Dose 40-60 uCi (1-1.6 MBq)/kg up to 4 mCi (148 MBq); dose can be repeated after 3-4 months
Pure beta emitter (1.49 MeV maximum energy; mean: 0.58 MeV), maximum path length: 8 mm; average path length: 2.4 mm
Bremsstrahlung imaging possible, but not practical
Used in patients with moderate pain, reasonable life expectancy (> 3 months) due to long response duration
P-32
First tracer used for metastatic bone pain palliation
Not widely used for bone pain palliation since 1980s; now abandoned
t1/2: 14.3 days
Pure beta emitter
Bremsstrahlung imaging possible, but not practical
Major drawback: Normal marrow receives high radiation dose relative to metastatic deposits (→ myelosuppression)
Also used to treat hematologic disease, primarily polycythemia vera
Rhenium 186 (Re-186)
t1/2: 90 hours
Not approved in United States
Similar to technetium, labeled to bisphosphonate
Gamma emission (187 keV) suitable for imaging
High radiation dose to normal bone
Tin 117m (Sn-117m), lutetium 177 (Lu-177)
Primarily investigational
Not currently in clinical use
Mechanism of action
Not well understood
Localized radiation to metastatic sites
May ↓ tumor volume
Likely ↓ in circulating cytokine, humoral factors that sensitize and stimulate nerve endings
PREPROCEDURE
Indications
Contraindications
Getting Started
PROCEDURE
Procedure Steps
Alternative Procedures/Therapies
POST PROCEDURE
Expected Outcome
OUTCOMES
Problems
Complications
Selected References
Den RB et al: Ra-223 treatment for bone metastases in castrate-resistant prostate cancer: Practical management issues for patient selection. Am J Clin Oncol. 42(4):399-406, 2019
Abi-Ghanem AS et al: Radionuclide therapy for osseous metastases in prostate cancer. Semin Nucl Med. 45(1):66-80, 2015
Shore ND: Radium-223 dichloride for metastatic castration-resistant prostate cancer: The urologist's perspective. Urology. 85(4):717-24, 2015
Pandit-Taskar N et al: Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride. J Nucl Med. 55(2):268-74, 2014
Wadas TJ et al: Molecular targeted α-particle therapy for oncologic applications. AJR Am J Roentgenol. 203(2):253-60, 2014
Wieder HA et al: Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters. World J Radiol. 6(7):480-5, 2014
Parker C et al: Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 369(3):213-23, 2013
Chiacchio S et al: Radionuclide therapy and integrated protocols for bone metastases. Q J Nucl Med Mol Imaging. 55(4):431-47, 2011
Bauman G et al: Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review. Radiother Oncol. 75(3):258-70, 2005
Damerla V et al: Recent developments in nuclear medicine in the management of bone metastases: a review and perspective. Am J Clin Oncol. 28(5):513-20, 2005
Liepe K et al: Systemic radionuclide therapy in pain palliation. Am J Hosp Palliat Care. 22(6):457-64, 2005
Liepe K et al: The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain. J Cancer Res Clin Oncol. 131(1):60-6, 2005
Pinski J et al: Prostate cancer metastases to bone: pathophysiology, pain management, and the promise of targeted therapy. Eur J Cancer. 41(6):932-40, 2005
Reisfield GM et al: Radiopharmaceuticals for the palliation of painful bone metastases. Am J Hosp Palliat Care. 22(1):41-6, 2005
Lam MG et al: 186Re-HEDP for metastatic bone pain in breast cancer patients. Eur J Nucl Med Mol Imaging. 31 Suppl 1:S162-70, 2004
Maini CL et al: 153Sm-EDTMP for bone pain palliation in skeletal metastases. Eur J Nucl Med Mol Imaging. 31 Suppl 1:S171-8, 2004
Pandit-Taskar N et al: Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 45(8):1358-65, 2004
Sapienza MT et al: Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy. Rev Hosp Clin Fac Med Sao Paulo. 59(6):321-8, 2004
Sartor O et al: Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 63(5):940-5, 2004
Ashayeri E et al: Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience. J Natl Med Assoc. 94(8):706-11, 2002
Lewington VJ: A practical guide to targeted therapy for bone pain palliation. Nucl Med Commun. 23(9):833-6, 2002
Giammarile F et al: Bone pain palliation with strontium-89 in cancer patients with bone metastases. Q J Nucl Med. 45(1):78-83, 2001
Hamdy NA et al: The palliative management of skeletal metastases in prostate cancer: use of bone-seeking radionuclides and bisphosphonates. Semin Nucl Med. 31(1):62-8, 2001
Han SH et al: 186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases. Q J Nucl Med. 45(1):84-90, 2001
STATdx includes over 200,000 searchable images, including x-ray, CT, MR, and ultrasound images. To access all images, please log in or subscribe.