¹⁶¹Tb has decay properties similar to those of ¹⁷⁷Lu but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply ¹⁶¹Tb in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of ¹⁶¹Tb-DOTATOC. Methods:¹⁶¹Tb 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 ¹⁶¹Tb-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 ¹⁶¹Tb-DOTATOC. Results: The radiolabeling of DOTATOC with ¹⁶¹Tb was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of ¹⁶¹Tb-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 ¹⁶¹Tb-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 ¹⁶¹Tb-DOTATOC using γ-scintigraphy and SPECT/CT. On the basis of this essential first step in translating ¹⁶¹Tb to clinics, further efforts will be directed toward the application of ¹⁶¹Tb for therapeutic purposes. Visual Abstract

The existence of theragnostic pairs of radionuclides allows the preparation of radiopharmaceuticals for diagnostic and therapeutic purposes. Radiolanthanides, such as ¹⁷⁷Lu, are successfully used for therapeutic purposes; however, a perfect diagnostic match is currently not available for clinical use. A unique, multi-disciplinary study was performed using ¹⁵²Tb (T_1/2 = 17.5 h, Eβ⁺ _average = 1140 keV, Iβ⁺ = 20.3%), which resulted in the first-in-human PET/CT images with this promising radionuclide. For this purpose, ¹⁵²Tb was produced via a spallation process followed by mass separation at ISOLDE, CERN. The chemical separation and quality control, performed at PSI, resulted in a pure product in sufficient yields. Clinical PET phantom studies revealed an increased image noise level, because of the smaller β⁺ branching ratio of ¹⁵²Tb as compared to standard PET nuclides at matched activity concentrations; however, the expected recovery would be comparable at matched signal-to-noise ratios in clinical PET. ¹⁵²Tb was used for labeling DOTATOC, at Zentralklinik Bad Berka, and administered to a patient for a first-in-human clinical study. PET scans were performed over a period of 24 h, allowing the visualization of even small metastases with increased tumor-to-background contrast over time. Based on the results obtained in this work, it can be deduced that PET/CT imaging with ¹⁵²Tb-labeled targeting agents has promise for clinical application and may be particularly interesting for pre-therapeutic dosimetry.

Purpose: PSMA-targeted radioligand therapy (PRLT) is a promising treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, a high uptake of the radiopharmaceutical in the salivary glands (SG) can lead to xerostomia and becomes dose-limiting for ²²⁵Ac-PSMA-617. This study investigated the sialotoxicity of ¹⁷⁷Lu-PSMA-I&T/-617 monotherapy and co-administered ²²⁵Ac-PSMA-617 and ¹⁷⁷Lu-PSMA-617 (Tandem-PPRLT). Methods: Three patient cohorts, that had undergone ¹⁷⁷Lu-PSMA-I&T/-617 monotherapy or Tandem-PRLT, were retrospectively analyzed. In a short-term cohort (91 patients), a xerostomia assessment (CTCAE v.5.0), a standardized questionnaire (sXI), salivary gland scintigraphy (SGS), and SG SUVmax and the metabolic volume (MV) on ⁶⁸Ga-PSMA-11-PET/CT were obtained before and after two cycles of ¹⁷⁷Lu-PSMA-I&T/-617. In a long-term cohort, 40 patients were similarly examined. In a Tandem cohort, the same protocol was applied to 18 patients after one cycle of Tandem-PRLT. Results: Grade 1 xerostomia in the short-term follow-up was observed in 22 (24.2%) patients with a worsening of sXI from 7 to 8 at (p < 0.05). In the long-term cohort, xerostomia grades 1 to 2 occurred in 16 (40%) patients. SGS showed no significant changes, but there was a decline of the MV of all SGs. After Tandem-PRLT, 12/18 (66.7%) patients reported xerostomia grades 1 to 2, and the sXI significantly worsened from 9.5 to 14.0 (p = 0.005), with a significant reduction in the excretion fraction (EF) and MV of all SGs. Conclusion: ¹⁷⁷Lu-PSMA-I&T/-617 causes only minor SG toxicity, while one cycle of Tandem-PRLT results in a significant SG impairment. This standardized protocol may help to objectify and quantify SG dysfunction.

Purpose: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. Methods: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. Results: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. Conclusion: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics.

To determine whether the TKTL1 protein epitope detection in monocytes (EDIM) test allows detection of upregulated glucose metabolism in malignancies. The EDIM-TKTL1 blood test was conducted in 240 patients with 17 different confirmed or suspected malignancies. Test scores were compared with (18)F-fluoro-2-deoxy-D-glucose (FDG)-PET/computed tomography (CT) results. EDIM-TKTL1 score and FDG-PET results showed a concordance of 90% with a sensitivity of 94% and specificity of 81%. Including CT data, all values were enhanced. A subgroup analysis of non-small-cell lung cancer patients showed a significant correlation between the EDIM-TKTL1 score and the primary tumor size determined by FDG-PET/CT. EDIM-TKTL1 blood test revealed good concordance with FDG-PET/CT results in patients with malignancies demonstrating its efficacy to detect upregulation of glucose metabolism in primary tumors or metastases.