Preclinical evaluation of Sm-153-DOTMP as a therapeutic bone-seeking radiopharmaceutical

1751 Objectives High-dose bone-seeking radiopharmaceuticals have been investigated for treating conditions such as breast cancer bone metastasis or multiple myeloma. Bartlett et al. have reported a saturation effect within the range of desirable administered activities of high-dose Sm-153-EDTMP. Sm-153-DOTMP (1, 4, 7, 10-tetraazacyclododecanetetramethylenephosphonic acid) is theoretically superior because of its more favorable chelant-to-metal ratio (1.5:1 vs. 273:1). This study in a rat model looked for a saturation effect for high-dose Sm-153-DOTMP and assessed its biodistribution. Methods Five cohorts of seven Sprague-Dawley rats, weighing 275±11.1 g, were administered Sm-153-DOTMP using a tail vein injection. The dosage consisted of 100 uCi of Sm-153 and sufficient Sm-152 to simulate 8, 16, 24, 32, or 40 mCi administered activity at a chelant-to-metal ratio of 1.5:1 in a volume of 100 uL for the five cohorts respectively. These dosages correspond to 2, 4, 6, 8 and 10 Ci in human beings. The animals were sacrificed 3.09±0.11 hours after administration. Blood, heart, lung, liver, spleen, kidney, muscle, stomach, intestines, femur and excreta were collected and assayed. Then, three cohorts of seven rats were administered simulated dosages of 40 mCi of Sm-153-DOTMP, sacrificed at 2, 24, and 48 hours respectively, and processed as above. Results In the saturation study, the slope of the linear regression for each of the sampled tissues of the percentage administered activity (%ID) vs. dosage was not significantly different from zero (p Conclusions Sm-153-DOTMP does not exhibit a saturation effect at dosages equivalent to those that would be administered to human beings for therapy with curative intent. The biodistribution and clearance of Sm-153-DOTMP is favorable for a bone-seeking, therapeutic radiopharmaceutical. Research Support NCI R43CA150601