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

Abstract

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with ((117m)Sn labelled) Sn(II) complexed to the bone seeking bisphosphonate, N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD, Pamindronate). This work is performed to utilise the idea that the low bone marrow radio toxicity of (117m)Sn could afford a highly effective radiopharmaceutical in pain palliation but also in the curative treatment of bone metastasis. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca(2+), Mg(2+), Zn(2+) as well as the added metal ion, Sn(2+) were measured by glass electrode potentiometry at 25 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from tests on a rodent model. The ((117m)Sn-labelled) Sn(II)-APDDMP complex was found to have only some liver and bone uptake although a high trabecular to normal bone ratio was recorded. From the blood plasma model this was shown to be primarily due to the high affinity of APDDMP for Ca(II) causing some of the Sn(II)-APDDMP complex to dissociate. High kidney uptake and excretion as well as high bladder uptake was recorded which was shown to be due to the dissociation of the Sn(II)-APDDMP complex in blood plasma. Animal model observations could be explained by the blood plasma modelling.

• Authors: Jan Rijn Zeevaart, David R Jansen, M Filomena Botelho, Antero Abrunhosa, Celia Gomes, Luiz Metello, Zvonimir I Kolar, Gerard C Krijger, Werner K A Louw, Irene C Dormehl
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 98 Issue 9 Pg. 1521-30 (Sep 2004) ISSN: 0162-0134 [Print] United States
• PMID: 15337604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkenes
• Blood Proteins
• Diphosphonates
• Ligands
• N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate
• Radiopharmaceuticals
• Tin

Topics

• Alkenes (blood, chemistry, metabolism, pharmacokinetics)
• Animals
• Blood Proteins (metabolism)
• Diphosphonates (blood, chemistry, metabolism, pharmacokinetics)
• Humans
• Ligands
• Models, Animal
• Models, Molecular
• Potentiometry
• Protein Binding
• Radiopharmaceuticals (blood, chemistry, metabolism, pharmacokinetics)
• Rats
• Tin (blood, chemistry, metabolism, pharmacokinetics)
• Tissue Distribution