Thermodynamic evaluation of the stability of the bone-seeking radiopharmaceutical [177Lu]Lu(III)-DOTP under simulated blood plasma conditions.
The stability and in vivo robustness of [(177)Lu]Lu-DOTP as a potential bone-targeting radiopharmaceutical was determined with the aid of thermodynamic blood plasma modeling simulations. Glass electrode potentiometry was employed to measure the stability constants of the complexes of Lu(3+) with DOTP. Similarly, the complexes of DOTP with a selection of the important physiological metal ions: Ca(2+), Mg(2+), and Cu(2+) were determined, representing the typical interactions that the ligand would encounter upon administration. This made possible the construction of a blood plasma model of DOTP, aiding in establishing the potential susceptibility of the radiopharmaceutical. The ligand binds predominantly to calcium in vivo, accounting for 59.6% of that initially introduced as a component of the Lu-DOTP complex. Furthermore, due to a preference of the DOTP to bind to Cu(2+) it causes mobilization of the ions in blood plasma, and would therefore indicate a deficiency if the ligand is administered at a concentration of 8.5 × 10(-5) mol dm(-3). The lutetium-ions are preferentially bound to DOTP, with as much as 98.1% of the Lu(3+) occupying the ligand under physiological conditions.
Radiochemistry, Department of Applied Chemistry, Necsa, South African Nuclear Energy Corporation Ltd., Pretoria, South Africa.
Lebogang C
LC
Sepini
Neil V
NV
Jarvis
David R
DR
Jansen
Jan Rijn
JR
Zeevaart
D001859:Bone Neoplasms / Q000532:radiotherapy; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D056831:Coordination Complexes / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000097:blood / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D008024:Ligands; D008274:Magnesium / Q000097:blood / Q000378:metabolism; D008954:Models, Biological; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D010146:Pain / Q000532:radiotherapy; D011199:Potentiometry; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
C575343:(177Lu)Lu(III)1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methane-phosphonic acid); D056831:Coordination Complexes; D008024:Ligands; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D003300:Copper; D008274:Magnesium; D002118:Calcium