Blood plasma model predictions for the proposed bone-seeking radiopharmaceutical [(117m)Sn]Sn(IV)-N,N',N'-trimethylenephosphonate-poly(ethyleneimine).
In an attempt to elucidate the in vivo stability of the prospective radiopharmaceutical [(117m)Sn]Sn(IV)-PEI-MP, where PEI-MP stands for N,N',N'-trimethylenephosphonate-polyethyleneimine, glass electrode potentiometry was used to determine the stability constants of the Sn(4+) ion as complexed with a variety of physiological amino acids. In addition, linear free energy relationship (LFER) correlation plots were used to extrapolate the constants of the major blood plasma ligands, based on data from Cu(2+), Pb(2+), and Zn(2+). In so doing, a thermodynamic model of blood plasma was established for Sn(4+) from which the complexation tendencies of Sn(4+) were predicted in the event of the intravenous administration of such a drug. It was found that the Sn(IV)-PEI-MP could succumb to competition by the glutamine amino acid, which forms more stable complex(es), whilst the PEI-MP gets taken up largely by Ca(2+). Also, this study shows the value of the in vitro experiments and modeling performed for radiopharmaceutical research and for attempts to reduce the number of animal experiments.
Jansen
David R
DR
Department of Applied Chemistry, South African Nuclear Energy Corporation Ltd., Pretoria, South Africa. davidj@necsa.co.za
Krijger
Gerard C
GC
Wagener
Judith
J
Senwedi
Ratanang M
RM
Gabanamotse
Kenneth
K
Kgadiete
Mpho
M
Kolar
Zvonimir I
ZI
Zeevaart
Jan Rijn
JR
D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002264:Carboxylic Acids / Q000097:blood / Q000378:metabolism; D003198:Computer Simulation; D016208:Databases, Factual; D004355:Drug Stability; D005973:Glutamine / Q000097:blood / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D015394:Molecular Structure; D009947:Organotin Compounds / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011199:Potentiometry; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011878:Radiotherapy; D014004:Tin Radioisotopes / Q000097:blood / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D002264:Carboxylic Acids; D008024:Ligands; D009947:Organotin Compounds; D019275:Radiopharmaceuticals; C544097:Sn(IV)-N,N',N'-trimethylenephosphonate-poly(ethyleneimine); D014004:Tin Radioisotopes; D005973:Glutamine; D002118:Calcium