Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging

Terbium-155 [T_1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the clinically established indium-111 and would be a useful substitute for the diagnosis and prospective dosimetry with biomolecules that are afterwards labeled with therapeutic radiolanthanides and pseudo-radiolanthanides, such as lutetium-177 and yttrium-90. Moreover, terbium-155 could form part of the perfect "matched pair" with the therapeutic radionuclide terbium-161, making the concept of true radiotheragnostics a reality. The aim of this study was the investigation of the production of terbium-155 via the ¹⁵⁵Gd(p,n)¹⁵⁵Tb and ¹⁵⁶Gd(p,2n)¹⁵⁵Tb nuclear reactions and its subsequent purification, in order to obtain a final product in quantity and quality sufficient for preclinical application. The ¹⁵⁶Gd(p,2n)¹⁵⁵Tb nuclear reaction was performed with 72 MeV protons (degraded to ~ 23 MeV), while the ¹⁵⁵Gd(p,n)¹⁵⁵Tb reaction was degraded further to ~ 10 MeV, as well as performed at an 18 MeV medical cyclotron, to demonstrate its feasibility of production.

The ¹⁵⁶Gd(p,2n)¹⁵⁵Tb nuclear reaction demonstrated higher production yields of up to 1.7 GBq, however, lower radionuclidic purity when compared to the final product (~ 200 MBq) of the ¹⁵⁵Gd(p,n)¹⁵⁵Tb nuclear reaction. In particular, other radioisotopes of terbium were produced as side products. The radiochemical purification of terbium-155 from the target material was developed to provide up to 1.0 GBq product in a small volume (~ 1 mL 0.05 M HCl), suitable for radiolabeling purposes. The high chemical purity of terbium-155 was proven by radiolabeling experiments at molar activities up to 100 MBq/nmol. SPECT/CT experiments were performed in tumor-bearing mice using [¹⁵⁵Tb]Tb-DOTATOC.

This study demonstrated two possible production routes for high activities of terbium-155 using a cyclotron, indicating that the radionuclide is more accessible than the exclusive mass-separated method previously demonstrated. The developed radiochemical purification of terbium-155 from the target material yielded [¹⁵⁵Tb]TbCl₃ in high chemical purity. As a result, initial cell uptake investigations, as well as SPECT/CT in vivo studies with [¹⁵⁵Tb]Tb-DOTATOC, were successfully performed, indicating that the chemical separation produced a product with suitable quality for preclinical studies.