Determination of stability constants in Y-DTPA-peptide-systems: Evaluationof a radiochemical method using n.c.a. Yttrium-88

Stability constants of various Yttrium-DTPA-peptides (DTPA: diethylenetriam inepentaacetic acid) were measured by a radiochemical method using no-carri er-added (n.c.a.) Y-88. The stability constants were calculated via a ligan d-ligand competition reaction with EDTA (ethylenediaminetetraacetic acid) a s the competing ligand. The radiochemical method was first evaluated by cal culating the overall stability constants (log beta) of Y-CDTA (CDTA: trans- 1,2-cyclohexyldiaminotetraacetic acid) in the Y-88/EDTA/CDTA system. The pr otonation constants of CDTA and the overall stability constant of Y-CDTA we re in good accordance with data determined by potentiometric titration. Sub sequently, the protonation constants and stability constants of three DTPA- peptides, DTPA-Phe-Gyl-Gly, DTPA-Phe-Trp and DTPA-Phe-Tyr were determined. The protonation constants were comparable to potentiometric titration data. The resulting stability constants of the corresponding Y-88-complexes show ed the same course shown by similar Gd-DTPA-systems. Finally, the overall s tability constant of Y-DTPA-(D)-Phe(1)-octreotide, a promising candidate in the field of nuclear medicine was determined. The overall stability consta nt was log beta = 19.25, indicating a stability loss of 3 magnitudes compar ed to Y-DTPA (log beta = 22.05) due to the occupation of one coordinating s ite.