Samarium Sm 153 lexidronam is a radioactive medication used to treat pain caused by cancer: A Review

Mr. Mayur S. Jain¹, Dr. Shashikant D. Barhate²

¹Neri, Tal. Jamner, Dist.- Jalgaon (Maharashtra)

²Institutional affiliation: Shree Sureshadada Jain Institutes of Pharmaceutical Education and Research, Jammer, Maharashtra (India)

*Corresponding Author E-mail: mayurjain176@gmail.com

ABSTRACT:

Samarium Sm 153 lexidronam is a radioactive medication used to treat pain caused by cancer that has spread to the bone. It is a radiopharmaceutical. Radiopharmaceuticals are radioactive agents that may be used to diagnose some diseases by studying the function of the body's organs or to treat certain diseases. Samarium Sm 153 lexidronam is used to help relieve the bone pain that may occur with certain kinds of cancer. The radioactive samarium is taken up in the bone cancer area and gives off radiation that helps provide relief of pain.

KEYWORDS: Samarium Sm 153 lexidronam.

INTRODUCTION:

Samarium Sm 153 lexidronam targets the sites of new bone formation, concentrating in regions of the bone that have been invaded with metastatic tumor. The drug goes to the source of cancer bone pain and irradiates the osteoblastic tumor sites resulting in relief of pain. The onset of pain relief was experienced as early as one week in the majority of patients.

Samarium (¹⁵³Sm) lexidronam (chemical name Samarium-153-ethylene diamine tetramethylene phosphonate, abbreviated Samarium-153 EDTMP, trade name Quadramet) is a chelated complex of a radioisotope of the element samarium with EDTMP. It is used to treat pain when cancer has spread to the bone.^[1]^[2]

It is injected into a vein and distributed throughout the body, where it is preferentially absorbed in areas where cancer has invaded the bone. The radioisotope ¹⁵³Sm, with a half-life of 46.3 hours, decays by emitting beta particles (electrons), which kill the nearby cells. Pain begins to improve in the first week for most people and the effects can last several months. It is commonly used in lung cancer, prostate cancer, breast cancer, and osteosarcoma. ^[1]

The pentasodium salt of samarium Sm 153 lexidronam, a therapeutic agent consisting of a medium energy beta- and gamma-emitting radioisotope, samarium Sm 153, and a teraphosphonate chelator, ethylenediamine tetramethylene phosphonic acid (EDTMP). The chelator moiety of samarium Sm 153 lexidronam associates with hydroxyapatite crystals concentrated in areas of bone turnover, thereby selectively delivering samarium Sm 153-mediated cytotoxic radiation to osteoblastic bone metastases. Check for active clinical trials using this agent ^[1]^[2]

Samarium-153 emits both medium-energy beta particles and an imageable gamma photon, and has a period of 46.3 hours (1.93 days). The primary radiation emissions of samarium-153 are shown in Table 1.

TABLE 1: SAMARIUM-153 PRINCIPAL RADIATION EMISSION DATA

Radiation	Energy (keV)	Abundance
Beta	640	30%
Beta	710	50%
Beta	810	20%
Gamma	103	29%

Maximum energies are listed for the beta emissions, the average beta particle energy is 233 keV.

External Radiation:

The specific gamma-ray constant for samarium-153 is 0.46 R/mCi-hr at 1 cm (1.24×10-5 mSv/MBq- hr at 1 Meter). The half-value thickness of lead (Pb) for samarium-153 is approximately 0.10 mm. The use of 1 mm of lead will decrease the external radiation exposure by a factor of approximately 1,000. QUADRAMET® should be stored in a lead-shielded container and frozen until use.

Structure:

(153Sm) samarium (3+) ion hydrogen {[(hydrogen phosphonomethyl) ({2- [(hydrogen phosphonomethyl) (phosphonomethyl)amino] ethyl}) amino] methyl} phosphonate

Chemical formula: C₆H₁₇N₂O₁₂

Weight: Average: 586.021. Monoisotopic: 585.895290894

Physical Characteristics:

Samarium-153 is produced in high yield and purity by neutron irradiation of isotopically enriched samarium Sm 152 oxide (152Sm2O3). It emits both medium-energy beta particles and a gamma photon, and has a physical half-life of 46.3 hours (1.93 days). Samarium-153 has average and maximum beta particle ranges in water of 0.5 mm and 3.0 mm, respectively

Indication:

Investigated for use/treatment in bone metastases, multiple myeloma, prostate cancer, and rheumatoid arthritis.

Route of administration:

Intravenous

Mechanism of action:

Clinical Pharmacology:

QUADRAMET® (samarium Sm-153 EDTMP) has an affinity for bone and concentrates in areas of bone turnover in association with hydroxyapatite. In clinical studies employing planar imaging techniques, more QUADRAMET® accumulates in osteoblastic lesions than in normal bone with a lesion-to-normal bone ratio of approximately 5. The mechanism of action of QUADRAMET® in relieving the pain of bone metastases is not known.

Pharmacodynamics:

The beta particle of 153Sm-EDTMP travels a maximum distance of 3.0 mm in soft tissue and 1.7 mm in bone. In clinical trials of 78 patients with metastatic bone lesions who had 13 specific bone scan sites evaluated, the presence or absence of 153Sm-EDTMP uptake is similar to the presence or absence of 99mTc diphosphonate uptake (range 67 to 96% agreement depending upon the blinded reader and the site of the body). Whether the amount of 153Sm-EDTMP uptake varies with the size of the lesion or to the presence of osteolytic components has not been studied. The clinical benefit of Sm-153-EDTMP in patients with osteolytic lesions is not known. The relationship of different tumor cell types to clinical response has not been studied.

Metabolism:

The complex formed by samarium and EDTMP is excreted as an intact, single species that consists of one atom of the Sm-153 and one molecule of the EDTMP, as shown by an analysis of urine samples from patients (n=5) administered samarium Sm-153 EDTMP. Metabolic products of samarium Sm-153 EDTMP were not detected in humans. ^[3]^[4]

Elimination:

For QUADRAMET®, calculations of the % ID detected in the whole body, urine and blood were corrected for radionuclide decay. The clearance of activity through the urine is expressed as the cumulated activity excreted. The whole body retention is the simple reciprocal of the cumulated urine activity. (See Skeletal Uptake Section).

Blood:

Clearance of radioactivity from the blood demonstrated biexponential kinetics after intravenous injection in 19 patients (10 men, 9 women) with a variety of primary cancers that were metastatic to bone. Over the first 30 minutes, the radioactivity (mean ± SD) in the blood decreased to 15% (±8%) of the injected dose with a t 1/2 of 5.5 min (±1.1 min). After 30 minutes, the radioactivity cleared from the blood more slowly with a t1/2 of 65.4 min (± 9.6 min). Less than 1% of the dose injected remained in the blood 5 hr after injection.

Urine:

Samarium Sm-153 EDTMP radioactivity was excreted in the urine after intravenous injection. During the first 6 hours, 34.5% (±15.5%) was excreted. Overall, the greater the number of metastatic lesions, the less radioactivity was excreted.

Information for Patients:

Patients who receive QUADRAMET® should be advised that for several hours following administration, radioactivity will be present in excreted urine. To help protect themselves and others in their environment, precautions need to be taken for 12 hours following administration. Whenever possible, a toilet should be used, rather than a urinal, and the toilet should be flushed several times after each use. Spilled urine should be cleaned up completely and patients should wash their hands thoroughly. If blood or urine gets onto clothing, the clothing should be washed separately, or stored for 1-2 weeks to allow for decay of the Sm-153.

Some patients have reported a transient increase in bone pain shortly after injection (flare reaction). This is usually mild and self-limiting and occurs within 72 hours of injection. Such reactions are usually responsive to analgesics.

Patients who respond to QUADRAMET® might begin to notice the onset of pain relief one week after QUADRAMET®. Maximal pain relief generally occurs at 3-4 weeks after injection of QUADRAMET®. Patients who experience a reduction in pain may be encouraged to decrease their use of opioid analgesics. ^[3]^[4]

Side effects:

· Black, tarry stools

· Blood in urine/stool

· Cough, hoarseness

· Fever/chills

· Lower back/side pain

· Painful or difficult urination

· Pinpoint red spots on skin

· Irregular heartbeat

· Nausea, vomiting

Contraindications:

Hypersensitivity to the active substance (ethylenediaminetetramethylenephosphonate (EDTMP) or similar phosphonates)., in pregnant women, in patients having received chemotherapy or hemi-body external radiation therapy in a preceding period of 6 weeks.

Pharmaceutical Form:

Solution for injection. Clear, colourless to light amber solution

PH Range:

Between 7.0 and 8.5

Storage:

Store frozen at -10° to -20°C (14° to -4°F) in a lead shielded container.

CONCLUSION:

ACKNOWLEDGEMENT:

The authors would like to thanks Shree. Sureshadada Jain Institutes of Pharmaceutical Education and Research, Jamner Maharashtra (India) for supporting the fulfillment of this work.

CONFLICT OF INTEREST:

Declared none.

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Received on 10.12.2019 Modified on 10.01.2020

Asian J. Pharm. Res. 2020; 10(1):48-51.

DOI: 10.5958/2231-5691.2020.00010.6