Quadramet (samarium Sm-153 EDTMP) has an affinity for bone and concentrates in areas of bone turnover in association with hydroxya-patite. 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.

Distribution: Human protein binding has not been studied; however, in dog, rat and bovine studies, less than 0.5% of samarium-153 EDTMP is bound to protein. At physiologic pH, >90% of the complex is present as ¹⁵³Sm[EDTMP]^-5, and <10% as ¹⁵³SmH[EDTMP]^-4. The octanol/ water partition coefficient is <10^-5.

Skeletal Uptake: The greater the number of metastatic lesions, the more skeletal uptake of Sm-153 radioactivity. The relationship between skeletal uptake and the size of the metastatic lesions has not been studied. The total skeletal uptake of radioactivity was 65.5% ± 15.5% of the injected dose in 453 patients with metastatic lesions from a variety of primary malignancies. In a study of 22 patients with a wide range in the number of metastatic sites, the % of the injected dose (% ID) taken up by bone ranged from 56.3% in a patient with 5 meta-static lesions to 76.7% in a patient with 52 metastatic lesions. If the number of metastatic lesions is fixed, over the range 0.1 to 3.0 mCi/ kg, the % ID taken up by bone is the same regardless of the dose.

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.

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 t_1/2 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.

Gender Differences: Gender did not affect the samarium Sm-153 EDTMP blood pharmacoki-netics, the cumulative % of radioactivity excreted in urine, or the % radioactivity retained in the skeleton when the number of metastatic lesions is taken into account.

Elderly: The pharmacokinetics of samarium Sm-153 EDTMP did not change with age as seen from comparison of values from people in the age range of 22 to 64 compared to the range 65 to 86 years.

Hepatic Insufficiency: Samarium Sm-153 EDTMP scintiscans in 5 patients with metastatic bone disease did not reveal accumulation of activity in the liver or the intestine; this suggests that hepatobiliary excretion did not occur.

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