Radioimmunotherapy of EGFR-positive tumors with 90Y-labeled panitumumab

Objectives Panitumumab (Vectibix) is the first FDA-approved fully human anti-EGFR mAb for solid tumors treatment. We evaluate the therapeutic efficacy of ⁹⁰Y-Panitumumab in UM-22B human head and neck cancer xenografted mice.

Methods Panitumumab was conjugated with DOTA for ¹¹¹In and ⁹⁰Y labeling. Biodistribution and imaging studies were carried out with ¹¹¹In-Panitumumab. For the therapy study, animals received 100 mCi and 200 mCi of ⁹⁰Y-Panitumumab, as well as saline, Panitumumab and 100 mCi of ⁹⁰Y-IgG, respectively. Histopathologic analyses were performed on liver and kidney tissues.

Results ¹¹¹In-Panitumumab exhibited high tumor uptake, with %ID/g 26.10±4.93, 59.11±7.22, 44.57±9.80, 40.38±7.76 and 14.86±7.23 at 4 h, 24 h, 72 h, 120 h and 168 h p.i., respectively. The liver uptake was relatively higher than other normal tissues, with %ID/g 15.71±1.36, 15.23±1.87, 10.67±1.48, 8.57±0.35 and 7.05±3.37 at the corresponding time points, respectively. With respect to therapy studies, the tumors in saline and Panitumumab groups showed fast growth, while the tumors in ⁹⁰Y-IgG group showed a little growth delay as compared with saline and Vectibix. In the 100 mCi ⁹⁰Y-Panitumumab group, no tumor growth was observed before 20 d posttreatment. During the 50 days of observation, no tumor growth was displayed in 200 mCi ⁹⁰Y-Panitumumab group. There was no obvious liver and kidney damage to mice as determined by histopathology.

Conclusions The high tumor uptake and long tumor retention, as well as the therapeutical efficacy reveal that ⁹⁰Y-Panitumumab is a promising radioimmunotherapeutic agent for the therapy of EGFR-positive solid tumors.