Evaluation of a chloride-based 89Zr isolation strategy using a tributyl phosphate (TBP)-functionalized extraction resin

Abstract

TBP-functionalized resin appears promising for the direct isolation of Zr-chloride from irradiatedY targets. Excellent Zr recovery efficiencies were obtained, and chemical purity was sufficient for proof-of-concept chelation studies.

Re-Evaluations of Zr-DFO Complex Coordination Chemistry for the Estimation of Radiochemical Yields and Chelator-to-Antibody Ratios of 89Zr Immune-PET Tracers

“…The competition titration of Zr vs Y to DFO eliminated the concern about Y, as even excess amounts of Y (even Y/Zr ≥ 10 4 or Y/DFO ≥ 10 2 ) did not inhibit the complexation of Zr-DFO. The amount of Y was about ~10 −5 mol/L in the purified 89 Zr solution [ 28 ]. Considering that purified 89 Zr solution is diluted 10-fold in radiolabeling reaction, the concentration of Y in radiolabeling reaction is estimated to be about ~10 −6 mol/L.…”

Preparation of Zirconium-89 Solutions for Radiopharmaceutical Purposes: Interrelation Between Formulation, Radiochemical Purity, Stability and Biodistribution

“…The evaluation of the resin suitability for zirconium-89 separation from solutions of an irradiated target was not the goal of this work, and these experiments are in future plans. At the same time, the effectiveness of ZR-resin for the isolation of zirconium-89 from target solutions has already been demonstrated by Graves et al [50], thus there is no reason to think that the purification in our case can go any other way. We did carry out experiments on metal impurities using model solutions (Y, Cu, and Fe added with the concentration of 25 mg/L) and MP-AES.…”

“…Since today there are publications describing the possibility of synthesizing zirconium-89 complexes with macrocyclic ligands (DOTA, etc.) exhibiting high stability [48,50], and such reactions require heating, we studied the stability of the preparations obtained by using zirconium-89 when heated. From the results, zirconium-89 preparations in 0.1 M sodium citrate solution (pH 6) did not withstand heating, in contrast to 1.0 M sodium citrate solutions and 0.1 M sodium oxalate solutions with the same pH values.…”

“…Thus, it is likely that the difference in the yield of complexation of zirconium-89 with macrocyclic ligands, shown in [48], may be due not only to the transformation of zirconium-89 from one to another chemical form, but also due to the influence of the concentration of oxalate anion itself on the reactivity these chelators. In addition, the observed difference in the measured average apparent molar activity of obtained [ 89 Zr]Zr-DOTA complexes for TBP-separated [ 89 Zr]Zr-chloride (oxalate-free) and QMA-reconstituted [ 89 Zr]Zr-chloride [50] is probably related to the presence of residual oxalic acid and the presence of zirconium-89 in the form of oxalate complexes after the reconstitution (and, therefore, with the degree of hydrolysis of zirconium-89).…”

“…Unfortunately, today, there are few papers describing the processes of using ZR-resin to isolate zirconium-89. Noteworthy is the work of Graves et al, who carried out the evaluation of the suitability of tributylphosphate(TBP)-impregnated solid-phase resin (TrisKem International) for the isolation of zirconium-89 [50]. As a comparison, a ZR-resin was used.…”