Targeted β^--Particle Plus Conversion and Auger-Electron Therapy with ¹⁶¹Tb-Labeled Somatostatin Receptor Antagonist...

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Therapy
• Oncology

Background:

• Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often treated with somatostatin receptor-targeted radiopharmaceuticals.
• Comparing the dosimetry and safety of different radiolabeled somatostatin analogs is crucial for optimizing therapy.
• [161Tb]Tb-DOTA-LM3 and [177Lu]Lu-DOTATOC are emerging agents for peptide receptor radionuclide therapy (PRRT).

Purpose of the Study:

• To determine and compare the absorbed doses in tumors and organs following administration of [161Tb]Tb-DOTA-LM3 and [177Lu]Lu-DOTATOC.
• To evaluate the safety and tolerability of [161Tb]Tb-DOTA-LM3 in patients with GEP-NETs.

Main Methods:

• A randomized, crossover, prospective, open-label phase 0 study involving 8 patients with grade 1-2 GEP-NETs.
• Patients received 1 GBq of [161Tb]Tb-DOTA-LM3 and 1 GBq of [177Lu]Lu-DOTATOC, separated by a 4-week interval.
• Quantitative SPECT/CT imaging was performed at multiple time points post-injection to calculate absorbed doses using 3D dosimetry.

Main Results:

• [161Tb]Tb-DOTA-LM3 demonstrated a significantly higher median tumor absorbed dose (36.6 Gy/GBq) compared to [177Lu]Lu-DOTATOC (7.0 Gy/GBq).
• Median effective tumor half-lives were longer for [161Tb]Tb-DOTA-LM3 (103 h) than for [177Lu]Lu-DOTATOC (83 h).
• Absorbed doses to kidneys and bone marrow were higher with [161Tb]Tb-DOTA-LM3, but the tumor-to-bone marrow absorbed dose ratio was similar for both agents.
• Grade 1-3 treatment-emergent adverse events occurred in 6 of 8 patients after [161Tb]Tb-DOTA-LM3 administration, with no relevant serious adverse events reported.

Conclusions:

• [161Tb]Tb-DOTA-LM3 achieved a 7.6-fold higher median tumor absorbed dose than [177Lu]Lu-DOTATOC, suggesting potentially greater therapeutic efficacy.
• The safety profile of 1 GBq [161Tb]Tb-DOTA-LM3 was acceptable, with a comparable tumor-to-bone marrow absorbed dose ratio to [177Lu]Lu-DOTATOC.
• These findings support the potential of [161Tb]Tb-DOTA-LM3 as a promising radiopharmaceutical for PRRT in GEP-NETs.