Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model

Comparison of the predicted in vivo behaviour of the Sn(II)–APDDMP complex and the results as studied in a rodent model

“…The liver organ mainly traps neutral and positively charged molecules. Animal experiments [8] confirmed that indeed 166 Ho-APDDMP is taken up in various organs while 153 Sm-APDDMP showed good bone uptake although less than 153 Sm-EDTMP [4]. Due to increased negative charge on the complexes only slight liver uptake was observed, confirming the importance of charge in designing radiopharmaceuticals [8].…”

“…Although more of APDDMP stays bound in blood plasma than the last two, not nearly as much Sn(II) stays bound to AP-DDMP as is the case with PEI-MP. The reason for this is the high affinity of APDDMP for Ca(II) and Mg(II) as seen in Table 3 which compares the values for AP-DDMP and PEI-MP in blood plasma at concentrations LOH 20.73 ± 0.03 2Sn + L-2H ¡ Sn 2 L(OH) 2 13.04 ± 0.03 2Sn + L-3H ¡ Sn 2 L(OH) 3 3.45 ± 0.03 2Sn + L-4H ¡ Sn 2 L(OH) 4 )6.93 ± 0.05 Sn + L ¡ SnL 15.26 ± 0.02 Sn + L-H ¡ SnL(OH) 6.51 ± 0.03…”

“…This abbreviations will be used throughout the article for all labelled compounds.) In studies undertaken to elucidate the in vivo behaviour of 153 Sm-EDTMP [3,4] the use of the blood plasma model evaluation of constituent concentration in large equilibrium systems (ECCLES) [5] proved to be particularly useful and was found to predict closely the clinical observations. ECCLES was further used in successive research on other bisphosphonates and phosphonate ligands, viz., methylenediphosphonic acid (MDP), 1-hydroxy-ethylenediphosphonic acid (HEDP) [6], 1-hydroxy-3-aminopropylidenediphosphonic acid (APD) [7], N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylide-nediphosphonate (APDDMP) [8] and, recently, polyethyleneimine functionalised with methylene phosphonate groups (PEI-MP) [9][10][11].…”

Application of radioisotopes in the field of nuclear medicine

“…In vivo behavior of 153Sm-EDTMP is independent of the amount of EDTMP at 1 hour post injection but at 24 hour post injection the liver uptake of this complex significantly decreases whereas bone uptake decreases lightly with increasing amount of injected EDTMP. [51][52][53][54][55] It has been observed that 153Sm particulate hydroxyapatite (153Sm-HYP) has two major advantages, namely, the particle size can be controlled prior the radiolabeling procedure and particulate hydroxyapatite is a natural constituent of bone. 56 The clinical outcome and tolerability of 153Sm-HYP was evaluated in patients with persistent rheumatoid knee synovitis.…”

Development of 166Ho-pamidronate for bone pain palliation therapy

“…The use of bisphosphonates has made a significant change in the therapeutic approach to management of bone metastasis and pain prevention in breast cancer and multiple myeloma [4]. Various therapeutic 166 Ho bone-seeking agents have been reported such as 166 Ho-DOTMP [5,6], 166 Ho-EDTMP [7,8], 166 Ho-AP-DDMP [9], as well as 166 Dy/ 166 Ho-EDTMP demonstrating adequate properties as a stable in vivo generator system for bone marrow ablation [10].…”