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

2020.09.25.

Falco Reissig et al., MDPI Pharmaceuticals, 2021

Summary

Barium-131 is a single photon emission computed tomography (SPECT)-compatible radionuclide for nuclear medicine and a promising diagnostic match for Radium-223/-224. In the early 1970s, Barium-131 has been thoroughly investigated as a potential bone targeting radiotracer, but no substantial benefits have been mentioned, comparing it to other already applicable radiotracers like [18F]F (t½ = 110 min) and 99mTc-labeled (t½ = 6.0 h) bisphosphonates. However, as part of current approaches to the therapy of bone cancer and bone metastases, this radionuclide has its significance in modern times. Barium-131 possesses the suitable half-life of 11.5 d, thereby making it highly beneficial for potential diagnostic use in nuclear medicine. Due to the similar chemistry and pharmacological properties of the elements Barium and Radium, Barium-131 is particularly feasible as a diagnostic match to the therapeutic α-emitters Radium-223 and Radium-224. In the work presented here, the authors aimed to establish a simple but sufficient procedure for the production and purification of n.c.a. Barium-131 using the TR-FLEX cyclotron (ACSI), starting from a cheap Cesium Chloride target with natural monoisotopically occurring Cesium followed by 27.5 MeV proton bombardment. Moreover, the in-house produced Barium-131 was used for first labeling studies with the chelator macropa, for initial in vivo-related phantom studies and, last but not least, small animal imaging trials with [131Ba]Ba(NO3)2 and 131Ba-labeled macropa in healthy mice.

Results from the nanoScan SPECT/CT

For the small animal imaging, the authors have used a nanoScan SPECT/CT, to follow the biodistribution with the different Barium-131 tracers.
SPECT/CT imaging in mice was performed at 1 h and 24 h after i.v. injection of [131Ba]Ba(NO3)2 (6.2 MBq in 0.2 mL of 0.01 M HNO3, pH 6, Am = 420 GBq/µmol, n.c.a.), or 131Ba-labeled macropa (6.7 MBq in 0.2 mL of 0.1 M ammonium acetate, pH 6, Am = 83 MBq/µmol) with a frame time of 60 s (total scan time: 1.5 h), respectively. The acquisition was performed using a standard aperture for mouse imaging (APT62) consisting of four M3 multi-pinhole collimators providing a 30 × 30 mm transaxial field of view (FOV). Projection data were reconstructed using the Tera-Tomo™ 3D high dynamic range algorithm (resolution: 128; iterations: 48; subset size: 4), applying corrections for decay, scatter, and attenuation.

Figure 8.shows the distribution of [131Ba]Ba(NO3)2 and [131Ba]Ba-macropa in mice. (A) SPECT/CT fusion images of [131Ba]Ba(NO3)2 in a mouse 1 h and 24 h after injection; (B,C) excretion profile and organ distribution of [131Ba]Ba(NO3)2 in mice 5 min, 1 h, and 24 h after injection (n = 4); (D) SPECT/CT fusion images of [131Ba]Ba-macropa in a mouse 1 h and 24 h after injection; (E,F) excretion profile and organ distribution of [131Ba]Ba-macropa in mice; 5 min, 1 h, and 24 h after injection (n = 4); (BAT) brown adipose tissue; (GB) gall bladder *; (ID) initial dose; (INT) intestine; (TD) thyroid/parathyroid *; (WAT) white adipose tissue (* activity in these organs was not measured separately).

  • The author have shown for the first time the in vivo biodistribution behavior of 131Ba-labeled macropa in comparison with free [131Ba]Ba2+ by means of small animal SPECT/CT.
  • 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. The authors have concluded 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.

Full article on mdpi.com

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