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

Abstract

Zirconium-89 is a promising radionuclide for nuclear medicine. The aim of the present work was to find a suitable method for obtaining zirconium-89 solutions for radiopharmaceutical purposes. For this purpose, the ion exchange behavior of zirconium-89 solutions was studied. Radio-TLC (thin layer chromatography) and biodistribution studies were carried out to understand speciation of zirconium-89 complexes and their role in the development of new radiopharmaceuticals. Three methods of zirconium-89 isolation were studied using ZR (hydroxamate) and Chelex-100 resins. It was found that ZR-resin alone is not enough to obtain stable zirconium-89 formulations. An easy and effective method of reconstitution of [89Zr]Zr-oxalate to [89Zr]Zr-citrate using Chelex-100 resin was developed. Developed procedures allow obtaining [89Zr]Zr-oxalate (in 0.1 M sodium oxalate solution) and [89Zr]Zr-citrate (in 0.1–1.0 M sodium citrate solution). These solutions are perfectly suitable and convenient for radiopharmaceutical purposes. Our results prove [89Zr]Zr-citrate to be advantageous over [89Zr]Zr-oxalate. During evaluation of speciation of zirconium-89 complexes, a new TLC method was developed, since it was proved that there is no comprehensive method for analysis or zirconium-89 preparations. The new method provides valuable insights about the content of “active” ionic form of zirconium-89. The interrelation of the chromatographic behavior of zirconium-89 preparations and their biodistribution was studied.

Multilayer Microcapsules with Shell-Chelated 89Zr for PET Imaging and Controlled Delivery

“…Unchelated 89 Zr as the oxalate salt has previously been employed in animal biodistribution models of radiotracers and has been shown to localize mainly (∼15% ID/ g at 6 days postinjection) in bone including the spine and femur as major sites. 58,59 Indeed, femur uptake was found to be low and was only 1.3 ± 0.1% ID/g in the athymic mice after 7 days, implying an excellent stability of 89 Zr−DFO and 89 Zr− TA complexes in the capsule shell (Figure 8, empty bar). For healthy mice, the bone (femur) uptake was found to be low reaching 4.1 ± 1.5% ID/g, which was 3-fold higher than that for athymic mice (Figure 8, dotted bar, *p < 0.05).…”

Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis

“…Considering the published results on the successful extraction of n.c.a. scandium radionuclides ( 43,44,47 Sc) using chelating resins Chelex 100 [13,[29][30][31] and NOBIAS Chelate-PA1 [32], as well as our results on the efficient isolation of medical radionuclides from oxalate solutions with Chelex 100 (e.g., 89 Zr [33]), this type of resin has also been tested for the recovery of scandium-44 from the generator eluate.…”

On the Versatility of Nanozeolite Linde Type L for Biomedical Applications: Zirconium-89 Radiolabeling and In Vivo Positron Emission Tomography Study

“…Increased beam energies (>17 MeV) might lead to higher radiochemical yields but are accompanied with the formation of long-lived byproducts, such as 88 Zr ( t 1/2 = 83.4 d) and 88 Y ( t 1/2 = 106.65 d) via the 89 Y­(p,2n) 88 Zr reaction . As these impurities represent a serious problem, the following steps of chelation of 89 Zr in the final PET agent and separation strategies are under close attention of radiochemists . The proposed methods to isolate 89 Zr from the target include extraction and chromatography by the exchange of either cations or anions .…”

“…22 As these impurities represent a serious problem, the following steps of chelation of 89 Zr in the final PET agent and separation strategies are under close attention of radiochemists. 23 The proposed methods to isolate 89 Zr from the target include extraction 24 and chromatography by the exchange of either cations 25 or anions. 26 Typically, ion-exchange is applied for which the target is first dissolved in concentrated HCl, then the resulting solution is passed through a column, and finally, desorption of 89 Zr is achieved by elution with a solution of oxalic acid in 1 M HCl.…”