Terbium offers 4 clinically interesting radioisotopes with complementary physical decay characteristics: ¹⁴⁹Tb, ¹⁵²Tb, ¹⁵⁵Tb, and ¹⁶¹Tb. The identical chemical characteristics of these radioisotopes allow the preparation of radiopharmaceuticals with identical pharmacokinetics useful for PET (¹⁵²Tb) and SPECT diagnosis (¹⁵⁵Tb) and for α- (¹⁴⁹Tb) and β⁻-particle (¹⁶¹Tb) therapy. The goal of this proof-of-concept study was to produce all 4 terbium radioisotopes and assess their diagnostic and therapeutic features in vivo when labeled with a folate-based targeting agent. Methods: ¹⁶¹Tb was produced by irradiation of ¹⁶⁰Gd targets with neutrons at Paul Scherrer Institute or Institut Laue-Langevin. After neutron capture, the short-lived ¹⁶¹Gd decays to ¹⁶¹Tb. ¹⁴⁹Tb, ¹⁵²Tb, and ¹⁵⁵Tb were produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. The isotopes were purified by means of cation exchange chromatography. For the in vivo studies, we used the DOTA–folate conjugate cm09, which binds to folate receptor (FR)–positive KB tumor cells. Therapy experiments with ¹⁴⁹Tb-cm09 and ¹⁶¹Tb-cm09 were performed in KB tumor–bearing nude mice. Diagnostic PET/CT (¹⁵²Tb-cm09) and SPECT/CT (¹⁵⁵Tb-cm09 and ¹⁶¹Tb-cm09) studies were performed in the same tumor mouse model. Results: Carrier-free terbium radioisotopes were obtained after purification, with activities ranging from approximately 6 MBq (for ¹⁴⁹Tb) to approximately 15 GBq (for ¹⁶¹Tb). The radiolabeling of cm09 was achieved in a greater than 96% radiochemical yield for all terbium radioisotopes. Biodistribution studies showed high and specific uptake in FR-positive tumor xenografts (23.8% ± 2.5% at 4 h after injection, 22.0% ± 4.4% at 24 h after injection, and 18.4% ± 1.8% at 48 h after injection). Excellent tumor-to-background ratios at 24 h after injection (tumor to blood, ∼15; tumor to liver, ∼5.9; and tumor to kidney, ∼0.8) allowed the visualization of tumors in mice using PET (¹⁵²Tb-cm09) and SPECT (¹⁵⁵Tb-cm09 and ¹⁶¹Tb-cm09). Compared with no therapy, α- (¹⁴⁹Tb-cm09) and β⁻-particle therapy (¹⁶¹Tb-cm09) resulted in a marked delay in tumor growth or even complete remission (33% for ¹⁴⁹Tb-cm09 and 80% for ¹⁶¹Tb-cm09) and a significantly increased survival. Conclusion: For the first time, to our knowledge, 4 terbium radionuclides have been tested in parallel with tumor-bearing mice using an FR targeting agent. Along with excellent tumor visualization enabled by ¹⁵²Tb PET and ¹⁵⁵Tb SPECT, we demonstrated the therapeutic efficacy of the α-emitter ¹⁴⁹Tb and β⁻-emitter ¹⁶¹Tb.

The fusion-evaporation reaction Pu244(Ca48,3-4n)114288,289 was studied at the new gas-filled recoil separator TASCA. Thirteen correlated decay chains were observed and assigned to the production and decay of 114288,289. At a compound nucleus excitation energy of E*=39.8\char21{}43.9\,\,MeV, the 4n evaporation channel cross section was 9.8-3.1+3.9\,\,pb. At E*=36.1\char21{}39.5\,\,MeV, that of the 3n evaporation channel was 8.0-4.5+7.4\,\,pb. In one of the 3n evaporation channel decay chains, a previously unobserved $\alpha${}~branch in Ds281 was observed (probability to be of random origin from background: 0.1%). This $\alpha${}~decay populated the new nucleus Hs277, which decayed by spontaneous fission after a lifetime of 4.5~ms.

The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging (68Ga) and radionuclide therapy (177Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced 44Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to 177Lu-PSMA-617. 44Sc was produced at the research cyclotron at PSI by irradiation of enriched 44Ca targets, followed by chromatographic separation. 44Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. 44Sc-PSMA-617 was evaluated in vitro and compared to the 177Lu- and 68Ga-labeled match, as well as 68Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of 177Lu- and 68Ga-labeled PSMA-617. Moreover, 44Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. 44Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of 44Sc-PSMA-617 resembled that of 177Lu-PSMA-617 most closely, while the 68Ga-labeled ligands, in particular 68Ga-PSMA-11, showed different distribution kinetics. 44Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed. The in vitro characteristics and in vivo kinetics of 44Sc-PSMA-617 were more similar to 177Lu-PSMA-617 than to 68Ga-PSMA-617 and 68Ga-PSMA-11. Due to the almost four-fold longer half-life of 44Sc as compared to 68Ga, a centralized production of 44Sc-PSMA-617 and transport to satellite PET centers would be feasible. These features make 44Sc-PSMA-617 particularly appealing for clinical application.