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 metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling.

Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals.

In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropililydenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic beta-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37 degrees C and I = 150 mmol dm-3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho-APD complex was taken up primarily by the liver due to precipitation or colloid formation.

Mechanistic studies of metal ion binding to water-soluble polymers using potentiometry.

A method for elucidating metal ion binding mechanisms with water-soluble polymers has been developed in which the polymer is treated as a collection of monomeric units. Data obtained from potentiometric titrations are analysed by the ESTA library of programs and apparent formation constants may be calculated. From this information, predictions may be made as to metal ion separation using complexation-ultrafiltration techniques. The polymer used in this study was Polymin Water-Free and its complexation with Hg(II), Cd(II), Pb(II), Co(II) and Ni(II) was successfully modelled.

Mechanistic studies of chelating resins using two-phase potentiometry.

The elucidation of metal ion binding mechanisms with chelating resins by treating the resin as a collection of monomeric units is an established approach. In this paper, this approach is used to treat data obtained from two-phase potentiometric titrations by the programme ESTA. Apparent protonation and formation constants could be calculated. From these, species distribution plots could be obtained. These, in turn, allowed the calculation of the more familiar distribution ratios. The method was tested on Fe(III) and Nd(III) bonding with the iminodiacetate functionalized resin, Chelex 100; and Ca(II) bonding to the aminomethylphosphonate functionalized resin, Purolite S940. Good results were obtained indicating the applicability of this method. Comparisons with the literature are made.