Recent insights in barium-131 as a diagnostic match for radium-223: cyclotron production, separation, labeling and imaging

Barium-131 is a promising SPECT-compatible radionuclide for nuclear medicine and a promising diagnostic match for the alpha emitters radium-223/-224 by providing similar chemical properties as well as physical half-lives. Methods: Herein, we report on the sufficient production route ¹³³Cs(p,3n)¹³¹Ba by using 28 MeV proton beams. Moreover, a sufficient purification process, based on SR Resin, was applied. For the first time, radiolabeling of macropa (literature-known chelator) with barium-131 was performed. Biodistribution studies and small animal SPECT/CT measurements were carried out with [¹³¹Ba]Ba(NO₃)₂ as reference and ¹³¹Ba-labeled macropa. Results: An average of 190 MBq barium-131 per irradiation was obtained. The purification process led to barium-131 in high radiochemical purity. Only an isotopic impurity of 0.01% barium-133 was detectable. Radiolabeling methods under mild conditions and reaction controls based on TLC systems were successfully applied for the labeling of the chelator macropa. For the first time, small animal SPECT imaging was performed using [¹³¹Ba]Ba(NO₃)₂ and ¹³¹Ba-labeled macropa in healthy mice. Biodistribution studies revealed the expected rapid bone uptake of [¹³¹Ba]Ba²⁺ ions, whereas ¹³¹Ba-labeled macropa showed a fast clearance from the blood, thereby showing a significantly (P < 0.001) lower accumulation in the bone. Conclusion: 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 for heavy alkaline earth metal ions, especially for radium isotopes. Those radionuclides and the necessary stable chelation are of great interest in the research field of targeted alpha therapy. Thereby, barium-131 will reveal its meaning as diagnostic match to the alpha emitters radium-223 and radium-224.