The radiolytic degradation of vector molecules is a major factor affecting the shelf life of therapeutic radiopharmaceuticals. The development of time-stable dosage forms of radiopharmaceuticals is the key to their successful implementation in clinical practice. Using [177Lu]Lu-PSMA-617 molecule as an example, the time dependence of the change in radiochemical purity (RCP, %) under radiolysis conditions was studied. The dependence of [177Lu]Lu-PSMA-617 radiolysis on parameters such as time, radionuclide activity, buffer agent concentration, precursor amount, and preparation volume was evaluated. It was shown that the absorbed dose was the dominant factor influencing the RCP. The RCP value is inversely proportional to the absorbed dose in the [177Lu]Lu-PSMA-617 preparation and has an exponential dependence. The lutetium-177 dose factor ψ (Gy·mL·MBq−1) and PSMA-617 concentration-dependent dose constant κ (Gy−1) were evaluated for absorbed dose estimation via computer modeling, chemical dosimetry, and radiochemical purity monitoring under various conditions. The further refinement and application of the dependencies found can be useful for predicting the RCP value at the stage of optimizing the composition of the finished dosage form of therapeutic radiopharmaceuticals. The influence of the buffer agent (sodium acetate) concentration on [177Lu]Lu-PSMA-617 radiolytic degradation was shown and should be considered both when developing a dosage form, and when comparing the results of independent studies. The effectiveness of the addition of various stabilizing agents, such as DMSA, cysteine, gentisic acid, vanillin, methionine, adenine, dobesilic acid, thymine, uracil, nicotinamide, meglumine, and mannitol, in suppressing the effects of radiolysis was evaluated.

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.

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.