[^203/212Pb]Pb-VMT-α-NET as a novel theranostic agent for targeted alpha radiotherapy-first clinical experience

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• Neuroendocrine tumors (NET) are a heterogeneous group of malignancies.
• Targeted alpha therapy (TAT) offers a promising approach for NET treatment.
• Lead-203/212 (Pb) is a theranostic isotope pair suitable for TAT.

Purpose of the Study:

• To investigate the clinical utility of [203/212Pb]Pb-VMT-α-NET for NET imaging and therapy.
• To assess the safety, biokinetics, and preliminary efficacy of this novel theranostic agent.

Main Methods:

• 12 patients with metastatic GEP-NET received diagnostic imaging with [203Pb]Pb-VMT-α-NET.
• Eligible patients received a single therapeutic dose of [212Pb]Pb-VMT-α-NET.
• Imaging and clinical parameters were monitored, with comparisons to [68Ga]Ga-DOTATATE PET.

Main Results:

• [203Pb]Pb-VMT-α-NET imaging demonstrated high, lesion-dependent intratumoral accumulation.
• Both diagnostic and therapeutic agents were well-tolerated, with no high-grade adverse effects.
• Post-treatment scans showed stable disease in all patients up to 3 months.

Conclusions:

• [203Pb]Pb-VMT-α-NET theranostics are well-tolerated and show promising efficacy in NET patients.
• This approach is effective even in heavily pretreated and heterogeneous patient populations.
• Further research is needed to evaluate long-term outcomes and efficacy with multiple cycles.