Biodistribution of Mesenchymal Stromal Cells Labeled with [89Zr]Zr-Oxine in Local Radiation Injuries in Laboratory Animals.

BACKGROUND: Tracking the migration pathways of living cells after their introduction into a patient's body is a topical issue in the field of cell therapy. Questions related to studying the possibility of long-term intravital biodistribution of mesenchymal stromal cells in the body currently remain open. METHODS: Forty-nine laboratory animals were used in the study. Modeling of local radiation injuries was carried out, and the dynamics of the distribution of mesenchymal stromal cells labeled with [89Zr]Zr-oxine in the rat body were studied. RESULTS: the obtained results of the labelled cell distribution allow us to assume that this procedure could be useful for visualization of local radiation injury using positron emission tomography. However, further research is needed to confirm this assumption. CONCLUSIONS: intravenous injection leads to the initial accumulation of cells in the lungs and their subsequent redistribution to the liver, spleen, and kidneys. When locally injected into tissues, mesenchymal stromal cells are not distributed systemically in significant quantities.

Synthesis, Complexation Properties, and Evaluation of New Aminodiphosphonic Acids as Vector Molecules for 68Ga Radiopharmaceuticals.

Two new aminodiphosphonic acids derived from salicylic acid and its phosphonic analogue were prepared through a simple and efficient synthesis. 2-[(2-Amino-2,2-diphosphono)ethyloxy]-benzoic acid 8 and 2-[(2-amino-2,2-diphosphono)ethyloxy]-5-ethyl-phenylphosphonic acid 9 were evaluated for their applicability as 68Ga binding bone-seeking agents. Protonation constants of 8 and 9 and stability constants of the Ga3+ complexes with 8 and 9 in water were determined. The stability constant of Ga3+ complex with fully phosphorylated acid 9 (logKGaL = 31.92 ± 0.32) significantly exceeds stability constant of Ga3+ complex with 8 (logKGaL = 26.63 ± 0.24). Ligands 8 and 9 are as effective for Ga3+ cation binding as ethylenediamine-N,N'-diacetic-N,N'-bis(methy1enephosphonic) acid and ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic) acid, respectively. The labelling process and stability of [68Ga]Ga-8 and [68Ga]Ga-9 were studied. Both 8 and 9 readily form 68Ga-complexes stable to ten-fold dilution with saline. However, in fetal bovine serum, only [68Ga]Ga-9 was stable enough to be subject to biological evaluation. It was injected into rats with bone pathology and aseptic inflammation of soft tissues. For [68Ga]Ga-9 in animals with a bone pathology model in 60 and 120 min after injection, a slight accumulation in the pathology site, stable blood percentage level, and moderate accumulation in the liver were observed. For animals with an aseptic inflammation, the accumulation of [68Ga]Ga-9 in the pathology site was higher than that in animals with bone pathology. Moreover, the accumulation of [68Ga]Ga-9 in inflammation sites was more stable than that for [68Ga]Ga-citrate. The percentage of [68Ga]Ga-9 in the blood decreased from 3.1% ID/g (60 min) to 1.5% ID/g (120 min). Accumulation in the liver was comparable to that obtained for [68Ga]Ga-citrate.

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.