Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals

In a quest for more effective radiopharmaceuticals for pain palliation of m etastatic bone cancer, this paper relates results obtained with Ho-166 and Sm-153 complexed to the bone seeking phosphonate, N,N-dimethylenephosphonat e 1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylid enediphosphonate (APD) and was complexed to lanthanide trivalent metal ions . This work is performed to utilise the idea that the energetic beta -parti cle emitter, Ho-166, coupled With phosphonate ligands such as APD and APDDM P could afford a highly effective radiopharmaceutical in the treatment of b one cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3and Sm3+ were measured by glass electrode potentiometry at 37 degreesC and 1=150 mM. Blood plasma models were constructed using the computer code ECCL ES and the results compared with those gathered from animal tests. The Ho-1 66-APDDMP complex was found to have little liver or bone uptake while Sm-15 3-APDDMP had a moderate bone uptake. This was primarily due to the high aff inity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling. (C) 2001 Elsevier Science B.V. All rights reserved .