[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT) has been applied to the treatment of neuroendocrine tumors (NETs) for over two decades. However, improvement is still needed, and targeted alpha (TAT) with emitters such as lead-212 (212Pb) represents a promising avenue. A series ligands based on octreotate was developed. Lead-203 used an imaging surrogate selection best candidate studies lead-212. 203/212Pb radiolabeling in vitro assays were carried out, followed by SPECT/CT ex vivo biodistribution NCI-H69 tumor-bearing mice. High radiochemical yields (≥99%) purity (≥96%) obtained all ligands. [203Pb]Pb-eSOMA-01 [203Pb]Pb-eSOMA-02 showed high stability PBS mouse serum up 24 h, whereas [203Pb]Pb-eSOMA-03 unstable those conditions. All compounds exhibited nanomolar affinity (2.5–3.1 nM) SSTR2. images revealed tumor uptake at 1, 4, h post-injection [203Pb]Pb-eSOMA-01/02. Ex confirmed that highest observed [212Pb]Pb-eSOMA-01. [212Pb]Pb-eESOMA-01 displayed absorbed dose (35.49 Gy/MBq) lowest kidneys (121.73 among three tested radioligands. [212Pb]Pb-eSOMA-01 NETs. Further investigations are required confirm its potential.