The impact of zirconium-89 solution formulation on the efficiency of [89 Zr]Zr-deferoxamine synthesis.

In recent years, clinical imaging with 89 Zr-based radiopharmaceuticals has been gaining significant importance in nuclear medicine. This article provides the results of a comparative study of methods for obtaining 89 Zr solutions using ZR, Chelex-100, and TBP resins in the form of [89 Zr]Zr-oxalate, [89 Zr]Zr-chloride, and [89 Zr]Zr-citrate in terms of purification and labeling efficiency. All evaluated methods allowed us to obtain 89 Zr with high yield (>90% in 1 ml). The chemical form of 89 Zr has a significant influence on the radiolabeling efficiency of the deferoxamine (DFO) chelator and its derivatives. Compared with [89 Zr]Zr-oxalate, the application of [89 Zr]Zr-chloride and [89 Zr]Zr-citrate solutions leads to a higher efficacy of [89 Zr]Zr-DFO complex formation. It should be noted that the sequence of mixing of the reagents during the radiolabeling reaction and the residual concentration of oxalic acid appeared to be crucial in the case of [89 Zr]Zr-chloride. According to the experimental data, radiolabeling of DFO and its derivatives is preferable to use more stable chemical forms of 89 Zr, such as [89 Zr]Zr-citrate. The concept will be applied in the further studies involving antibody-based bioconjugates.

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.

Today, 44Sc is an attractive radionuclide for molecular imaging with PET. In this work, we evaluated a 44Ti/44Sc radionuclide generator based on TEVA resin as a source of 44Sc. The generator prototype (5 MBq) exhibits high 44Ti retention and stable yield of 44Sc (91 ± 6 %) in 1 mL of eluate (20 bed volumes, eluent-0.1 M oxalic acid/0.2 M HCl) during one year of monitoring (more than 120 elutions). The breakthrough of 44Ti did not exceed 1.5 × 10-5% (average value was 6.5 × 10-6%). Post-processing of the eluate for further use in radiopharmaceutical synthesis was proposed. The post-processing procedure using a combination of Presep® PolyChelate and TK221 resins made it possible to obtain 44Sc-radioconjugates with high labeling yield (≥95%) while using small precursor amounts (5 nmol). The proposed method takes no more than 15 min and provides ≥90% yield relative to the 44Sc activity eluted from the generator. The labeling efficiency was demonstrated on the example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T synthesis. Some superiority of PSMA-I&T over PSMA-617 in terms of 44Sc labeling efficiency was demonstrated (likely due to presence of DOTAGA chelator in the precursor structure). It was also shown that microwave heating of the reaction mixture considerably shortened the reaction time and improved radiolabeling yield and reproducibility of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T synthesis.

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

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.