Evaluation of renal and hematologic toxicities of 212Pb-VMT-alpha-NET to inform the safety of alpha-particle therapy for neuroendocrine tumors

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Introduction: Lead-212 (212Pb) is an attractive alpha-particle emitter for SSTR2-targeted therapy for neuroendocrine tumors. We developed a new peptide structure (VMT-alpha-NET) specifically for Pb isotopes, and preclinical studies demonstrated that the peptide significantly improved therapeutic responses in SSTR2-positive tumors in mice (including 8/10 complete responses).

Aim(s): The aim of this study was to evaluate toxicities of 212Pb-VMT-alpha-NET in an animal model.

Materials and methods: Escalating doses of 212Pb-VMT-alpha-NET were administered to tumor-free CD-1 male mice. Bodyweight were monitored, and renal and hematologic toxicities were evaluated using kidney injury markers/histopathology and complete blood count analyses. A kidney dosimetry analysis was conducted using the DigiMouse voxel phantom based on 212Pb biodistribution data.

Conference: 18th Annual ENETS Concerence (2021)

Presenting Author:

Authors: Lee D, Li M, Liu D, Baumhover N, Sagastume E,

Keywords: PRRT, alpha-particle therapy, Pb-212, VMT-alpha-NET, toxicity,