Recent Insights in Barium-131 as a Diagnostic Match for Radium-223: Cyclotron Production, Separation, Radiolabeling, and Imaging

Abstract

Barium-131 is a single photon emission computed tomography (SPECT)-compatible radionuclide for nuclear medicine and a promising diagnostic match for radium-223/-224. Herein, we report on the sufficient production route 133Cs(p,3n)131Ba by using 27.5 MeV proton beams. An average of 190 MBq barium-131 per irradiation was obtained. The SR Resin-based purification process led to barium-131 in high radiochemical purity. An isotopic impurity of 0.01% barium-133 was detectable. For the first time, radiolabeling of the ligand macropa with barium-131 was performed. Radiolabeling methods under mild conditions and reaction controls based on TLC systems were successfully applied. Small animal SPECT/ computed tomography (CT) measurements and biodistribution studies were performed using [131Ba]Ba(NO3)2 as reference and 131Ba-labeled macropa in healthy mice for the first time. Biodistribution studies revealed the expected rapid bone uptake of [131Ba]Ba2+, whereas 131Ba-labeled macropa showed a fast clearance from the blood, thereby showing a significantly (p < 0.001) lower accumulation in the bone. We conclude that barium-131 is a promising SPECT radionuclide and delivers appropriate imaging qualities in small animals. Furthermore, the relative stability of the 131Ba-labeled macropa complex in vivo forms the basis for the development of sufficient new chelators, especially for radium isotopes. Thereby, barium-131 will attain its goal as a diagnostic match to the alpha emitters radium-223 and radium-224.

Towards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand

“…22) ¼ 1.42Å), 55 prompting its recent investigation as a chelator for the diagnostic isotope 131 Ba. 56 In aqueous solution at pH 7.4, the conditional stability constant ðlog K 0 ML;pH 7:4 Þ of the [Ba(macropa)] complex is 10.74 (I ¼ 0.1 M KCl, 25 C), indicating that macropa is the highest-affinity chelator for Ba 2+ at physiological pH reported to date. Based on these properties, we hypothesized that macropa might also be suitable for binding to Ra 2+ , the heavier alkaline earth ion congener of Ba 2+ , for TAT applications (Fig.…”

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution

“…A1). 133 Ba radionuclide is γ-emitter and is particularly feasible as a diagnostic match to the therapeutic α-emitter 223 Ra radionuclide [21].…”

“…Unfortunately, upon conjugation of MACROPA to DUPA, stability of radiocomplex was lost. Alternatively, several attempts have been made to incorporate 223 Ra into nanoparticle constructs such as liposomes [16,17], magnetite nanoparticles [18], CaCO 3 microparticles [19], hydroxyapatites and titanium dioxide nanoparticles [20], barium sulfate nanoparticles [21] and nanozeolites [22,23]. Recently, our group successfully designed and evaluated in vitro the 223 Ra-labeled and anti-PSMA targeted NaA nanozeolites ( 223 RaA-silane-PEG-D2B) for prostate cancer therapy [24].…”

Die Bedeutung des Elementes Barium in der Nuklearmedizin

“…Im Jahr 2020 verfolgte unsere Arbeitsgruppe die erneute Betrachtung des Radionuklids Barium-131 mit veränderter Zielstellung [7]. Basierend…”

“…Diese können aufgrund der ähnlichen chemischen und pharmakologischen Eigenschaften als bildgebende Surrogate für die therapeutischen Alphaund Beta(minus)-Emitter verwendet werden. Barium-131 wurde letztendlich als Radionuklid vorgeschlagen, welches sich in hohem Maß als diagnostisches Analogon für v. a. Radiumisotope eignet [7].…”