Targeted β ͞ -Particle Plus Conversion and Auger-Electron Therapy with 161Tb-Labeled Somatostatin Receptor Antagonist DOTA-LM3: A Phase 0 Study

Abstract

The goal of this phase 0 study was to determine the absorbed doses in tumors and relevant organs after a test injection of [161Tb]Tb-DOTALM3 and [177Lu]Lu-DOTATOC in the same cohort of patients with grade 1 and 2 somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. Methods: In this randomized, crossover, prospective, single-center, open-label phase 0 study, 8 patients received 1 GBq of [161Tb]Tb-DOTA-LM3 and 1 GBq of [177Lu]Lu-DOTATOC, with a 4-wk interval between injections. Quantitative SPECT/CT imaging was performed 3, 24, 72, and 168 h after administration of each radiopharmaceutical to calculate tumor and organ absorbed doses (3- dimensional dosimetry using a Monte Carlo–based ordered-subset expectation maximization algorithm). Results: After injection of 1 GBq of [161Tb]Tb-DOTA-LM3, SPECT/CT revealed excellent image quality with intense tumor uptake in all patients and a median of the mean effective tumor half-life of 103 h (range, 56–152 h) for [161Tb]Tb-DOTALM3 and 83 h (range, 30–122 h) for [177Lu]Lu-DOTATOC (P 5 0.012). The medians of the mean tumor absorbed doses of [161Tb]Tb-DOTALM3 and [177Lu]Lu-DOTATOC were 36.6 Gy/GBq (range, 15–196 Gy/ GBq) and 7.0 Gy/GBq (range, 2.4–14.2 Gy/GBq), respectively (P 5 0.008). The median kidney and bone marrow absorbed doses were 2.4 Gy/GBq (range, 1.8–3.1 Gy/GBq) and 0.31 Gy/GBq (range, 0.24–0.48 Gy/GBq) for [161Tb]Tb-DOTA-LM3 and 0.6 Gy/GBq (range, 0.4–0.8 Gy/GBq) and 0.04 Gy/GBq (range, 0.03–0.06 Gy/GBq) for [177Lu]Lu- DOTATOC, respectively (both P 5 0.008). According to Common Terminology Criteria for Adverse Events version 5.0, grade 1–3 treatment-emergent adverse events occurred in 6 of 8 patients after administration of 1 GBq of [161Tb]Tb-DOTA-LM3. Conclusion: [161Tb]Tb-DOTA-LM3 showed a 7.6-fold-higher median tumor absorbed dose than that of [177Lu]Lu-DOTATOC. The tumor–to–bone marrow absorbed dose ratio was in the same range for [161Tb]Tb- DOTA-LM3 as for [177Lu]Lu-DOTATOC. The administration of 1 GBq of [161Tb]Tb-DOTA-LM3 was safe for all patients, without relevant adverse events.