Hydroxyapatite chemisorption of N,N',N'-trimethylenephosphonate-poly(ethyleneimine) (PEI-MP) combined with Sn2+ or Sn4+.
To study the mechanism by which proposed bone-seeking radiopharmaceuticals consisting of tin (as l17mSn) and N,N',N'-trimethylenephosphonate-poly(ethyleneimine) (PEI-MP) are taken up and accumulated in bone tissue, the adsorption of Sn2+, Sn4+, and phosphonate polymer PEI-MP on hydroxyapatite was measured in vitro. Hydroxyapatite is the main mineral phase of bone; therefore, by determining the affinity of the metal ions and the ligand-and hence their complexes-for hydroxyapatite, the extent to which the radiopharmaceutical will be adsorbed can be predicted. The adsorption of the tin-phosphonate complexes and the two individual components to the solid phase was measured by inductively coupled plasma optical emission spectroscopy at physiological pH, at room temperature, and for a period of 48 h. The tin complexes and free ligand exhibited unique binding affinities. By varying the oxidation state of the metal ion (Sn2+, and Sn4+) and the size of the polyphosphonate ligand (using 10-30 and 30-50 kDa fractions), the adsorption characteristics of the individual components could be adapted. The tin-PEI-MP combination that showed the most favorable adsorption behavior was that of Sn2+ and PEI-MP(10-30 kDa), which had a maximum adsorption capacity of 2.21 +/- 0.14 micromol m(-2) and an affinity of 9.8 +/- 4.0 dm3 mmol(-1) with respect to the ligand and 2.30 +/- 0.07 micromol m(-2) and 26.6 +/- 6.1 dm3 mmol(-1) for the metal ion-as derived from the Langmuir adsorption model. The ligand showed enhanced adsorption when complexed with tin. This research provided a preliminary indication that the tin-PEI-MP combination could be favorable to other bone-seeking radiopharmaceuticals since the maximum adsorption capacities are comparable while PEI-MP offers the opportunity of using the enhanced permeability and retention effect for enhanced tumor accumulation.
Radiochemistry, Department of Applied Chemistry, Necsa (South African Nuclear Energy Corporation Ltd.), P.O. Box 582, Pretoria 0001, South Africa. davidj@necsa.co.za
David R
DR
Jansen
Jan Rijn
JR
Zeevaart
Antonia
A
Denkova
Zvonimir I
ZI
Kolar
Gerard C
GC
Krijger
D000327:Adsorption; D001842:Bone and Bones / Q000000981:diagnostic imaging; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D009369:Neoplasms / Q000532:radiotherapy; D063065:Organophosphonates / Q000737:chemistry; D009947:Organotin Compounds / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry; D013053:Spectrophotometry / Q000379:methods; D013499:Surface Properties; D013696:Temperature; D014001:Tin / Q000737:chemistry*
C489335:(polyethyleneiminomethyl phosphonate)tin(II); D008024:Ligands; D063065:Organophosphonates; D009947:Organotin Compounds; D019275:Radiopharmaceuticals; D014001:Tin; D011094:Polyethyleneimine; D017886:Durapatite