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The favorable decay characteristics of 161 Tb attracted the interest of clinicians in using this novel radionuclide for radioligand therapy (RLT). 161 Tb decays with a similar half-life to 177 Lu, but beyond the emission of β - -particles and γ-rays, 161 Tb also emits conversion and Auger electrons, which may be particularly effective to eliminate micrometastases. The aim of this study was to compare the dosimetry and therapeutic efficacy of 161 Tb and 177 Lu in tumor-bearing mice using SibuDAB and PSMA-I&T, which differ in their blood residence time and tumor uptake. Methods: [ 161 Tb]Tb-SibuDAB and [ 161 Tb]Tb-PSMA-I&T were evaluated in vitro and investigated in biodistribution, imaging, and therapy studies using PC-3 PIP tumor-bearing mice. The 177 Lu-labeled counterparts served for dose calculations and comparison of therapeutic efficacy. The tolerability of RLT in mice was monitored on the basis of body mass, blood plasma parameters, blood cell counts, and the histology of relevant organs and tissues. Results: The prostate-specific membrane antigen (PSMA)-targeting radioligands, irrespective of whether labeled with 161 Tb or 177 Lu, showed similar in vitro data and comparable tissue distribution profiles. As a result of the albumin-binding properties, [ 161 Tb]Tb/[ 177 Lu]Lu-SibuDAB had an enhanced blood residence time and higher tumor uptake (62%-69% injected activity per gram at 24 h after injection) than [ 161 Tb]Tb/[ 177 Lu]Lu-PSMA-I&T (30%-35% injected activity per gram at 24 h after injection). [ 161 Tb]Tb-SibuDAB inhibited tumor growth more effectively than [ 161 Tb]Tb-PSMA-I&T, as can be ascribed to its 4-fold increased absorbed tumor dose. At any of the applied activities, the 161 Tb-based radioligands were therapeutically more effective than their 177 Lu-labeled counterparts, as agreed with the approximately 40% increased tumor dose of 161 Tb compared with that of 177 Lu. Under the given experimental conditions, no obvious adverse events were observed. Conclusion: The data of this study indicate the promising potential of 161 Tb in combination with SibuDAB for RLT of prostate cancer. Future clinical studies using 161 Tb-based RLT will shed light on a potential clinical benefit of 161 Tb over 177 Lu., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

161 Tb is an interesting radionuclide for application in the treatment of neuroendocrine neoplasms' small metastases and single cancer cells because of its conversion and Auger-electron emission. Tb has coordination chemistry similar to that of Lu; therefore, like 177 Lu, it can stably radiolabel DOTATOC, one of the leading peptides used for the treatment of neuroendocrine neoplasms. However, 161 Tb is a recently developed radionuclide that has not yet been specified for clinical use. Therefore, the aim of the current work was to characterize and specify 161 Tb and to develop a protocol for the synthesis and quality control of 161 Tb-DOTATOC with a fully automated process conforming to good-manufacturing-practice guidelines, in view of its clinical use. Methods: 161 Tb, produced by neutron irradiation of 160 Gd in high-flux reactors followed by radiochemical separation from its target material, was characterized regarding its radionuclidic purity, chemical purity, endotoxin level, and radiochemical purity (RCP) in analogy to what is described in the European Pharmacopoeia for no-carrier-added 177 Lu. In addition, 161 Tb was introduced into a fully automated cassette-module synthesis to produce 161 Tb-DOTATOC, as used for 177 Lu-DOTATOC. The quality and stability of the produced radiopharmaceutical in terms of identity, RCP, and ethanol and endotoxin content were assessed by means of high-performance liquid chromatography, gas chromatography, and an endotoxin test, respectively. Results: 161 Tb produced under the described conditions showed, as the no-carrier-added 177 Lu, a pH of 1-2, radionuclidic purity and RCP of more than 99.9%, and an endotoxin level below the permitted range (175 IU/mL), indicating its appropriate quality for clinical use. In addition, an efficient and robust procedure for the automated production and quality control of 161 Tb-DOTATOC with clinically applicable specifications and activity levels, that is, 1.0-7.4 GBq in 20 mL, was developed. The radiopharmaceutical's quality control was also developed using chromatographic methods, which confirmed the product's stability (RCP ≥ 95%) over 24 h. Conclusion: The current study demonstrated that 161 Tb has appropriate features for clinical use. The developed synthesis protocol guarantees high yields and safe preparation of injectable 161 Tb-DOTATOC. The investigated approach could be translated to other DOTA-derivatized peptides; thus, 161 Tb could be successfully applied in clinical practice for radionuclide therapy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

161 Tb has decay properties similar to those of 177 Lu but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply 161 Tb in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of 161 Tb-DOTATOC. Methods: 161 Tb was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of 161 Tb-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar γ-scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of 161 Tb-DOTATOC. Results: The radiolabeling of DOTATOC with 161 Tb was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of 161 Tb-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of 161 Tb-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of 161 Tb-DOTATOC using γ-scintigraphy and SPECT/CT. On the basis of this essential first step in translating 161 Tb to clinics, further efforts will be directed toward the application of 161 Tb for therapeutic purposes., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)