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Combination of terbium-161 with somatostatin receptor antagonists—a potential paradigm shift for the treatment of neuroendocrine neoplasms.
- Source :
- European Journal of Nuclear Medicine & Molecular Imaging; Mar2022, Vol. 49 Issue 4, p1113-1126, 14p, 3 Charts, 6 Graphs
- Publication Year :
- 2022
-
Abstract
- Purpose: The β<superscript>¯</superscript>-emitting terbium-161 also emits conversion and Auger electrons, which are believed to be effective in killing single cancer cells. Terbium-161 was applied with somatostatin receptor (SSTR) agonists that localize in the cytoplasm (DOTATOC) and cellular nucleus (DOTATOC-NLS) or with a SSTR antagonist that localizes at the cell membrane (DOTA-LM3). The aim was to identify the most favorable peptide/terbium-161 combination for the treatment of neuroendocrine neoplasms (NENs). Methods: The capability of the <superscript>161</superscript>Tb- and <superscript>177</superscript>Lu-labeled somatostatin (SST) analogues to reduce viability and survival of SSTR-positive AR42J tumor cells was investigated in vitro. The radiopeptides' tissue distribution profiles were assessed in tumor-bearing mice. The efficacy of terbium-161 compared to lutetium-177 was investigated in therapy studies in mice using DOTATOC or DOTA-LM3, respectively. Results: In vitro, [<superscript>161</superscript>Tb]Tb-DOTA-LM3 was 102-fold more potent than [<superscript>177</superscript>Lu]Lu-DOTA-LM3; however, <superscript>161</superscript>Tb-labeled DOTATOC and DOTATOC-NLS were only 4- to fivefold more effective inhibiting tumor cell viability than their <superscript>177</superscript>Lu-labeled counterparts. This result was confirmed in vivo and demonstrated that [<superscript>161</superscript>Tb]Tb-DOTA-LM3 was significantly more effective in delaying tumor growth than [<superscript>177</superscript>Lu]Lu-DOTA-LM3, thereby, prolonging survival of the mice. A therapeutic advantage of terbium-161 over lutetium-177 was also manifest when applied with DOTATOC. Since the nuclear localizing sequence (NLS) compromised the in vivo tissue distribution of DOTATOC-NLS, it was not used for therapy. Conclusion: The use of membrane-localizing DOTA-LM3 was beneficial and profited from the short-ranged electrons emitted by terbium-161. Based on these preclinical data, [<superscript>161</superscript>Tb]Tb-DOTA-LM3 may outperform the clinically employed [<superscript>177</superscript>Lu]Lu-DOTATOC for the treatment of patients with NENs. [ABSTRACT FROM AUTHOR]
- Subjects :
- NEUROENDOCRINE tumors
TERBIUM
AUGER electrons
RADIOISOTOPES
CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 16197070
- Volume :
- 49
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- European Journal of Nuclear Medicine & Molecular Imaging
- Publication Type :
- Academic Journal
- Accession number :
- 156400546
- Full Text :
- https://doi.org/10.1007/s00259-021-05564-0