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.
Jansen
David R
DR
Radiochemistry, Department of Applied Chemistry, Necsa (South African Nuclear Energy Corporation Ltd.), P.O. Box 582, Pretoria 0001, South Africa. davidj@necsa.co.za
Zeevaart
Jan Rijn
JR
Denkova
Antonia
A
Kolar
Zvonimir I
ZI
Krijger
Gerard C
GC
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