Clinical evaluation of the radiolanthanide terbium-152: first-in-human PET/CT with $^152$Tb-DOTATOC

The existence of theragnostic pairs of radionuclides allows the preparation of radiopharmaceuticals for diagnostic and therapeutic purposes. Radiolanthanides, such as $^{177}$Lu, 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 $^{152}$Tb ($T_{1/2}$ = 17.5 h, E$\beta ^+_{average}$ = 1140 keV, I$β^+$ = 20.3%), which resulted in the first-in-human PET/CT images with this promising radionuclide. For this purpose, $^{152}$Tb 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 $\beta^+$ branching ratio of $^{152}$Tb 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. $^{152}$Tb 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 $^{152}$Tb-labeled targeting agents has promise for clinical application and may be particularly interesting for pre-therapeutic dosimetry.