Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours
Limited experiments have compared the treatment effects of repetitive cycles of radiolabelled somatostatin (SST) analogues. In vitro and in vivo experiments were conducted in an AR42J cancer cell model, comparing the antagonist [<sup>177</sup>Lu]Lu-satoreotide tetraxetan with the agonist...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/9/1085 |
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| author | Pascale Plas Lorenzo Limana Denis Carré Amath Thiongane Olivier Raguin Rosalba Mansi Florence Meyer-Losic Stéphane Lezmi |
| author_facet | Pascale Plas Lorenzo Limana Denis Carré Amath Thiongane Olivier Raguin Rosalba Mansi Florence Meyer-Losic Stéphane Lezmi |
| author_sort | Pascale Plas |
| collection | DOAJ |
| description | Limited experiments have compared the treatment effects of repetitive cycles of radiolabelled somatostatin (SST) analogues. In vitro and in vivo experiments were conducted in an AR42J cancer cell model, comparing the antagonist [<sup>177</sup>Lu]Lu-satoreotide tetraxetan with the agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in terms of their binding properties, biodistribution, anti-tumour activity and toxicity. Histopathological and immunohistochemical examinations were performed at different timepoints. In the in vitro assays, [<sup>177</sup>Lu]Lu-satoreotide tetraxetan recognised twice as many SST<sub>2</sub> binding sites as [<sup>177</sup>Lu]Lu-DOTA-TATE. In mice treated once a week for four consecutive weeks, [<sup>177</sup>Lu]Lu-satoreotide tetraxetan (15 MBq) revealed a significantly greater median time taken to reach a tumour volume of 850 mm<sup>3</sup> (68 days) compared to [<sup>177</sup>Lu]Lu-DOTA-TATE at 15 MBq (43 days) or 30 MBq (48 days). This was associated with a higher tumour uptake, enhanced DNA damage and no or mild effects on body weight, haematological toxicity, or renal toxicity with [<sup>177</sup>Lu]Lu-satoreotide tetraxetan (15 MBq). At the end of the study, complete tumour senescence was noted in 20% of animals treated with [<sup>177</sup>Lu]Lu-satoreotide tetraxetan, in 13% of those treated with [<sup>177</sup>Lu]Lu-DOTA-TATE at 30 MBq, and in none of those treated with [<sup>177</sup>Lu]Lu-DOTA-TATE at 15 MBq. In conclusion, repeated administrations of [<sup>177</sup>Lu]Lu-satoreotide tetraxetan were able to potentiate peptide receptor radionuclide therapy with a higher tumour uptake, longer median survival, and enhanced DNA damage, with a favourable efficacy/safety profile compared to [<sup>177</sup>Lu]Lu-DOTA-TATE. |
| first_indexed | 2024-03-09T22:52:29Z |
| format | Article |
| id | doaj.art-9b5dea50747d4fda984a66cc498c85c7 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:52:29Z |
| publishDate | 2022-08-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-9b5dea50747d4fda984a66cc498c85c72023-11-23T18:18:20ZengMDPI AGPharmaceuticals1424-82472022-08-01159108510.3390/ph15091085Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive TumoursPascale Plas0Lorenzo Limana1Denis Carré2Amath Thiongane3Olivier Raguin4Rosalba Mansi5Florence Meyer-Losic6Stéphane Lezmi7IPSEN Innovation, 91940 Les Ulis, FranceIPSEN Innovation, 91940 Les Ulis, FranceIPSEN Innovation, 91940 Les Ulis, FranceIPSEN Innovation, 91940 Les Ulis, FranceOncodesign, 21000 Dijon, FranceDivision of Radiopharmaceutical Chemistry, Clinic of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, 4031 Basel, SwitzerlandIPSEN Innovation, 91940 Les Ulis, FranceIPSEN Innovation, 91940 Les Ulis, FranceLimited experiments have compared the treatment effects of repetitive cycles of radiolabelled somatostatin (SST) analogues. In vitro and in vivo experiments were conducted in an AR42J cancer cell model, comparing the antagonist [<sup>177</sup>Lu]Lu-satoreotide tetraxetan with the agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in terms of their binding properties, biodistribution, anti-tumour activity and toxicity. Histopathological and immunohistochemical examinations were performed at different timepoints. In the in vitro assays, [<sup>177</sup>Lu]Lu-satoreotide tetraxetan recognised twice as many SST<sub>2</sub> binding sites as [<sup>177</sup>Lu]Lu-DOTA-TATE. In mice treated once a week for four consecutive weeks, [<sup>177</sup>Lu]Lu-satoreotide tetraxetan (15 MBq) revealed a significantly greater median time taken to reach a tumour volume of 850 mm<sup>3</sup> (68 days) compared to [<sup>177</sup>Lu]Lu-DOTA-TATE at 15 MBq (43 days) or 30 MBq (48 days). This was associated with a higher tumour uptake, enhanced DNA damage and no or mild effects on body weight, haematological toxicity, or renal toxicity with [<sup>177</sup>Lu]Lu-satoreotide tetraxetan (15 MBq). At the end of the study, complete tumour senescence was noted in 20% of animals treated with [<sup>177</sup>Lu]Lu-satoreotide tetraxetan, in 13% of those treated with [<sup>177</sup>Lu]Lu-DOTA-TATE at 30 MBq, and in none of those treated with [<sup>177</sup>Lu]Lu-DOTA-TATE at 15 MBq. In conclusion, repeated administrations of [<sup>177</sup>Lu]Lu-satoreotide tetraxetan were able to potentiate peptide receptor radionuclide therapy with a higher tumour uptake, longer median survival, and enhanced DNA damage, with a favourable efficacy/safety profile compared to [<sup>177</sup>Lu]Lu-DOTA-TATE.https://www.mdpi.com/1424-8247/15/9/1085[<sup>177</sup>Lu]Lu-satoreotide tetraxetan[<sup>177</sup>Lu]Lu-DOTA-TATEsomatostatin receptor subtype 2AR42Jpeptide receptor radionuclide therapy |
| spellingShingle | Pascale Plas Lorenzo Limana Denis Carré Amath Thiongane Olivier Raguin Rosalba Mansi Florence Meyer-Losic Stéphane Lezmi Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours Pharmaceuticals [<sup>177</sup>Lu]Lu-satoreotide tetraxetan [<sup>177</sup>Lu]Lu-DOTA-TATE somatostatin receptor subtype 2 AR42J peptide receptor radionuclide therapy |
| title | Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours |
| title_full | Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours |
| title_fullStr | Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours |
| title_full_unstemmed | Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours |
| title_short | Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [<sup>177</sup>Lu]Lu-Satoreotide Tetraxetan and the Agonist [<sup>177</sup>Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST<sub>2</sub>-Positive Tumours |
| title_sort | comparison of the anti tumour activity of the somatostatin receptor sst antagonist sup 177 sup lu lu satoreotide tetraxetan and the agonist sup 177 sup lu lu dota tate in mice bearing ar42j sst sub 2 sub positive tumours |
| topic | [<sup>177</sup>Lu]Lu-satoreotide tetraxetan [<sup>177</sup>Lu]Lu-DOTA-TATE somatostatin receptor subtype 2 AR42J peptide receptor radionuclide therapy |
| url | https://www.mdpi.com/1424-8247/15/9/1085 |
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