Comparison of Systemic Toxicities of 177Lu-DOTMP and 153Sm-EDTMP Administered Intravenously at Equivalent Skeletal Doses to Normal Dogs

Abstract

The dogs receiving (177)Lu-DOTMP tolerated the administration and the effects of the compound without apparent clinical toxicity. The results of this experiment support the further evaluation in tumor-bearing dogs of (177)Lu-DOTMP as a potential therapy for metastatic bone cancer and primary bone tumors in humans and dogs.

Proceedings of the Second NCI–SNMMI Workshop on Targeted Radionuclide Therapy

“…To evaluate 177 Lu-DOTMP toxicity, researchers from the University of Missouri studied the effects of radiopharmaceutical administration on dogs (2). The preliminary findings supported evaluation of the radiopharmaceutical as a potential therapy for primary and metastatic bone cancer in both dogs and humans.…”

Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153

“…This radiopharmaceutical causes less myelosuppression than an equivalent dose of 153 Sm-EDTMP (Bryan et al, 2009).…”

“…For example, the decay of 125 I has been shown to lead to the deposition of a very high dose (≈10 9 cGy/decaying atom) in the immediate vicinity (≈2 nm 3 ) of the decay site and a sharp and significant drop in the energy deposited (from ≈10 9 to ≈10 6 cGy) as a function of increasing distance (few nanometres) from the decaying 125 I atom (Kassis, 2011). For example, when 125 I is localized within the cytoplasm, the survival curve is of the low LET type and the number of decays needed to reduce survival is ≈80 times that of DNA-incorporated 125 I (Kassis, 2011 (Abbasi, 2012(Abbasi, , 2011Argyrou et al, 2013a;Bączyk, 2011;Bryan et al, 2009;Chakraborty et al, 2008;Daha et al, 2010;Das et al, 2009;Harrison et al, 2013;Lewington, 2005;Máthé et al, 2010;Neves et al, 2005;Nilsson et al, 2013bNilsson et al, , 2007Nilsson et al, , 2005aNilsson et al, , 2005bPandit-Taskar et al, 2014;Ramdahl et al, 2013;Sartor, 2004;Simón et al, 2012;Sivaprasad and Rajagopal, 2012;Tomblyn, 2012;Vigna et al, 2011;Volkert and Hoffman, 1999;Wang et al, 2011). Despite the growing number of radionuclides investigated for treatment of bone metastases, the use of 89 Sr and 153 Sm still accounts for the bulk of radiopharmaceutical bonetargeted therapeutics in the clinical context and the majority of the review articles available in the literature focus on those two radionuclides.…”

Production and quality control 177Lu (NCA)—DOTMP as a potential agent for bone pain palliation

“…The two most important criteria that determine the utility of any bone‐targeted radiopharmaceutical in a given situation are which radionuclide is being used and which site‐specific carrier is included (7) . Phosphonates carriers, such as EDTMP(diethylenetriamine penta(methylene phosphonic acid)), DOTMP(1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethylene phosphonic acid), APD(1‐hydroxy‐3‐ amino propylidene‐diphosphonic acid), TTHMP(Triehtylenetetramine hexamethylene phosphonate), are being used for the other radiopharmaceuticals that are site‐specific for skeletal lesions 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 . Low‐energy β ‐ emitting radionuclides, such as 177 Lu, 153 Sm, 175 Yb, and 186 Re, are used for palliation of bone pain, whereas radionuclides with higher energies including 166 Ho, 90 Y, and 188 Re are recommended for bone marrow ablation.…”