Samarium153 Lexidronam Edtmp Ethylenediaminetetramethylphosphonate

This radiopharmaceutical is a chelate holding the Sm-153 atom. At the hydroxy-apatite surface, an oxygen atom on a phosphonate moiety may coordinate with a calcium atom on the bone mineral surface. There is some evidence that samarium atoms may also be hydrolytically released at the hydroxyapatite surface because of a higher affinity of Sm-153 for oxygen atoms of the hydroxyapatite, forming samarium oxide. It is a gamma emitter but is far too expensive to be used to detect osteoblastic activity prior to administration of a larger therapeutic dose. Technetium (Tc)-99m-medronate or oxidronate is employed for this purpose. As with the other radiopharmaceuticals under consideration, skeletal retention is related to the extent of increased osteoblastic lesions throughout the skeleton. With a much shorter half-life than Sr-89, its dose rate is higher and much of the dose is delivered over the first two half-lives. Skeletal retention is complete by about six hours, with very little Sm-153 found in the urine thereafter. Reported response rates range from 55% to 80%, generally do not increase with dose escalation (although, predictably, myelotoxicity does), and are also independent of the tumor type treated.

There have been several placebo-controlled studies using Sm-153 lexidro-nam.The response rate from 1.0 mCi/kg was more rapid than that from 0.5 mCi/ kg, in one of these, but the clinical response was equivalent between the two groups after five weeks, and both were better than the placebo. There was mye-lotoxicity up to grade 3 or 4 in 10% of the patients, with recovery of depressed blood counts by about eight weeks. Marrow suppression was more severe in the presence of widespread metastases, previous chemotherapy or teletherapy, or with significant marrow involvement two other controlled studies have confirmed the efficacy of this treatment, with the higher dose (1.0 mCi/kg) showing a response greater than 0.5 mCi/kg in each of the first four weeks after injection. Response rates ranged between 55% and 70% and were not significantly different. The reduction in pain has been reported to last between 2 and 17 weeks, with one study claiming that 50% of responses lasted 16 weeks. In the blinded studies noted before, response duration averaged six weeks. Multiple dosages have been successfully given with repeated responses. In one study, a multiple dose regimen (two to four doses, separated by three-month intervals) led to a higher overall response than a single dosage. Because of the shorter half-life of Sm-153 (given as the lexidronman chelate) compared with Sr-89, there is a widespread belief that myelotoxicity resolves more quickly with Sm-153 lexidronam, but there are no studies directly comparing the two radiopharmaceuticals to provide confirmation of this.

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