Work

Targeted α-Particle Radiation Therapy of HER1-Positive Disseminated Intraperitoneal Disease: An Investigation of the Human Anti-EGFR Monoclonal Antibody, Panitumumab

Year: 2017

Type: article

Abstract: Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research. Panitumumab, a fully human and less immunogenic mAb that binds to the epidermal growth factor receptor (Erb1; HER1), was evaluated for targeted α-particle radiation therapy using 212 Pb, an in vivo α generator. A single dose of 212 Pb-panitumumab administered to athymic mice bearing LS-174T intraperitoneal (i.p.) tumor xenografts was found to have greater therapeutic efficacy when directly compared with 212 Pb-trastuzumab, which binds to HER2. A dose escalation study determined a maximum effective working dose of 212 Pb-panitumumab to be 20 μCi with a median survival of 35 days versus 25 days for the untreated controls. Pretreatment of tumor-bearing mice with paclitaxel and gemcitabine 24 hours prior to injection of 212 Pb-pantiumumab at 10 or 20 μCi resulted in the greatest enhanced therapeutic response at the higher dose with median survivals of 106 versus 192 days, respectively. The greatest therapeutic impact, however, was observed in the animals that were treated with topotecan 24 hours prior to RIT and then again 24 hours after RIT; the best response from this combination was also obtained with the lower 10-μCi dose of 212 Pb-panitumumab (median survival >280 days). In summary, 212 Pb-panitumumab is an excellent candidate for the treatment of HER1-positive disseminated i.p. disease. Furthermore, the potentiation of the therapeutic impact of 212 Pb-pantiumumab by chemotherapeutics confirms and validates the importance of developing a multimodal therapy regimen.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2017.04.004

Authors: Diane E. Milenic, Kwamena E. Baidoo, Young-Seung Kim, Rachel Barkley, Martin W. Brechbiel

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research

Language: English

Topic: Radiopharmaceutical Chemistry and Applications

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,390