[225Ac]Ac-SibuDAB

A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [⁶⁸ Ga]Ga-DOTATOC and [¹⁸F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [²²⁵Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [²²⁵Ac]Ac-DOTATOC 10 days after intraportal graft.

Liver tumors showed a high uptake of [⁶⁸ Ga]Ga-DOTATOC and no uptake of [¹⁸F]F-FDG confirming the well-differentiated phenotype. All groups treated with [²²⁵Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53 days with 240 kBq (p = 0.0001), and 58 days with 2 × 120 kBq (p < 0.0001) vs 28 days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings.

[²²⁵Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET.