First-in-Humans Application of 161Tb: A Feasibility Study Using 161Tb-DOTATOC

Abstract

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.

Keywords: 161Tb; Auger electrons; DOTATOC; SPECT/CT imaging; first-in-humans.

Graphical abstract

FIGURE 1.

Whole-body images of patient 1 at 0.5 h after injection (A), 3 h after injection (B), 24 h after injection (C), and 3 d (71 h) (D) after injection of ¹⁶¹Tb-DOTATOC. Images demonstrated physiologic biodistribution of ¹⁶¹Tb-DOTATOC in liver (Li), spleen (Sp), intestines (Int), and kidneys (Ki) and excretion into urinary bladder (Bl). In addition, accumulation in known osseous metastases (sternal manubrium [blue arrows] and orbital part of frontal bone on left [red arrow]) was visualized. p.i. = after injection.

FIGURE 2.

Fused coronal SPECT/CT images of patient 1 obtained on the second day after injection of ¹⁶¹Tb-DOTATOC. Images showed pathologic uptake of ¹⁶¹Tb-DOTATOC in osseous metastasis (sternal manubrium [red arrow]) (A) and physiologic uptake of ¹⁶¹Tb-DOTATOC in kidneys (Ki), liver (Li), and spleen (Sp) (B).

FIGURE 3.

Whole-body images of patient 2 at 0.5 h after injection (A), 2.5 h after injection (B), 20 h after injection (C), and 113 h after injection (D) of ¹⁶¹Tb-DOTATOC. Early blood-pool activity was noted in heart (H) and blood vessels (BV) up to 2.5 h after injection. Physiologic uptake of radiopeptide was observed in soft tissues, liver (Li), kidneys (Ki), intestines (Int) and urinary bladder (Bl). Pathologic accumulation of ¹⁶¹Tb-DOTATOC was demonstrated in bilobar liver (blue arrows) and multifocal osseous metastases (red arrows). p.i. = after injection.

FIGURE 4.

SPECT/CT images of patient 2 at 19 h after injection of ¹⁶¹Tb-DOTATOC. (A) Coronal section. (B) Sagittal section. (C) Transverse section. Images showed uptake of ¹⁶¹Tb-DOTATOC in bilobar hepatic metastases (yellow arrows) as well as multiple osteoblastic skeletal metastases in vertebral column and pelvis (red arrows). Physiologic uptake of ¹⁶¹Tb-DOTATOC was seen in both kidneys (Ki) as well as in liver (Li).

FIGURE 5.

PET/CT sagittal section of patient 1 at 60 min after injection of ⁶⁸Ga-DOTATOC. Pathologic uptake was seen in multiple skeletal metastases (sternal manubrium, left orbital part of frontal bone, occipital bone, and multiple vertebrae [red arrows]). Comparatively higher physiologic uptake of ⁶⁸Ga-DOTATOC was observed in spleen (Sp). Accumulation of activity in urinary bladder (Bl) was seen because of renal excretion of radiopeptide.