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

1
State Research Center—Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str., bld. 46; 123182 Moscow, Russian
2
Lomonosov Moscow State University, GSP-1, Leninskie Gory, 119991 Moscow, Russian
*
Author to whom correspondence should be addressed.
Academic Editors: Licia Uccelli, Alessandra Boschi and Petra Martini
Molecules 2019, 24(8), 1534; https://doi.org/10.3390/molecules24081534
Received: 28 February 2019 / Revised: 15 April 2019 / Accepted: 16 April 2019 / Published: 18 April 2019
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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. View Full-Text
Keywords: zirconium-89; purification; radiochemical purity; stability; DFO; transchelation; ZR hydroxamate resin; Chelex-100; oxalate; citrate zirconium-89; purification; radiochemical purity; stability; DFO; transchelation; ZR hydroxamate resin; Chelex-100; oxalate; citrate
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Larenkov, A.; Bubenschikov, V.; Makichyan, A.; Zhukova, M.; Krasnoperova, A.; Kodina, G. Preparation of Zirconium-89 Solutions for Radiopharmaceutical Purposes: Interrelation Between Formulation, Radiochemical Purity, Stability and Biodistribution. Molecules 2019, 24, 1534.

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