Antitumor activity comparison of two somatostatin receptor ligands radiolabeled with Lutetium-177 (SSO110 and DOTA-TATE)

• Published Abstract Number: 5044
• Autors :

Olivier Raguin⁽¹⁾, Marcel Krueger⁽²⁾, Peggy Provent⁽¹⁾, Funda Cay⁽²⁾, Elodie Marie Dit Chatel ⁽¹⁾, Marie Lux⁽¹⁾, Ben Pais⁽³⁾, Cyril Berthet⁽¹⁾

⁽¹⁾ Oncodesign-services, 21000 Dijon, France, ⁽²⁾ Werner Siemens Imaging Center, Germany, ⁽³⁾ SRT-Biomedical, Netherlands, consultant to Ariceum Therapeutics, Berlin, Germany

• Abstract :

Antitumor activity comparison of two somatostatin receptor ligands radiolabeled with Lutetium-177 (SSO110 and DOTA-TATE) alone or combined with chemotherapy in mice bearing AR42J SSTR2-Positive Tumors

Only a limited number of studies have compared the therapeutic effects of repetitive cycles of radiolabeled somatostatin (SST) analogues or assessed potential synergy of these analogues with chemotherapy agents.

Hence, a comparison was conducted in an in vivo AR42J tumor model with a SSTR2 antagonist, [¹⁷⁷Lu]Lu-satoreotide tetraxetan ([¹⁷⁷Lu]Lu‑SSO110), and a SSTR2 agonist, [¹⁷⁷Lu]Lu-DOTA-TATE. The efficacy of treatment combining [¹⁷⁷Lu]Lu-satoreotide tetraxetan with capecitabine plus temozolomide was also assessed.

Swiss Nude mice were xenografted with AR42J tumor cells. For the evaluation of the tumor response to radiation therapy, animals received one weekly dose of [¹⁷⁷Lu]Lu‑SSO110 or [¹⁷⁷Lu]Lu-DOTA-TATE for four consecutive weeks. For combined treatments, animals received one weekly dose of [¹⁷⁷Lu]Lu‑SSO110 at 20 MBq for four consecutive weeks in association with daily doses of capecitabine and temozolomide (CAPTEM).

Weekly treatment for four consecutive weeks with [¹⁷⁷Lu]Lu‑SSO110 at 15 MBq revealed a significantly reduced tumor growth, with 68 days to reach a tumor volume of 850 mm³, compared to [¹⁷⁷Lu]Lu-DOTA-TATE at 15 MBq or 30 MBq, with, respectively, 43 days and 48 days. This was associated with a 3.5 fold higher tumor uptake of [¹⁷⁷Lu]Lu‑SSO110 (15 MBq) compared to [¹⁷⁷Lu]Lu-DOTA-TATE, with no or mild effects on body weight, hematological toxicity, or renal toxicity.

In AR42J tumor-bearing mice treated once a week for four consecutive weeks, [¹⁷⁷Lu]Lu‑SSO110 (15 MBq) associated with CAPTEM regimen did not significantly increase the median time to reach a tumor volume of 1000 mm³ as compared to treatment with [¹⁷⁷Lu]Lu-satoreotide alone: 50.7 vs 42.2 days, respectively. The association of the two treatments only led to mild weight losses.

Repeated administrations of [¹⁷⁷Lu]Lu‑SSO110 were able to potentiate peptide receptor radionuclide therapy with a higher tumor uptake and longer median survival compared to [¹⁷⁷Lu]Lu-DOTA-TATE. The The combination of [¹⁷⁷Lu]Lu-satoreotide with capecitabine and temozolomide did not show any synergy, but no antagonism was observed either.

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