Acute cytotoxic effects of photoimmunotherapy assessed by 18F-FDG PET.

Abstract

We have recently developed a cancer-specific therapy, photoimmunotherapy, which uses an antibody-IR700 (phototoxic phthalocyanine dye) conjugate to bind to the cell membrane and near-infrared light to induce immediate and highly specific tumor killing in vivo. For monitoring the acute cytotoxic effects of photoimmunotherapy before the tumor begins to shrink, we used (18)F-FDG PET before and after this intervention in mice. Photoimmunotherapy was performed by binding panitumumab (anti-HER1)-IR700 to HER1-positive tumor cells (A431), followed by near-infrared light irradiation in vitro and in vivo. The uptake of (18)F-FDG in the tumor after photoimmunotherapy was evaluated in cellular uptake studies and PET imaging studies. Serial histologic analyses were conducted after photoimmunotherapy. The in vitro cellular uptake of (18)F-FDG was reduced as the dose of light increased, and at high light dose (2 J/cm(2)) the uptake was reduced by more than 99% within 1 h after photoimmunotherapy. In vivo (18)F-FDG PET imaging showed that the accumulation of radioactivity in the treated tumors decreased 76% at 75 min after photoimmunotherapy and did not change for 24 h. In contrast, no significant changes were demonstrated in nontreated tumors. None of tumors changed size within 24 h after photoimmunotherapy, although diffuse necrosis was observed in photoimmunotherapy-treated tumors. Immediate cytotoxic effects induced by photoimmunotherapy were clearly detected by decreased glucose uptake using (18)F-FDG PET even before changes in tumor size became evident. (18)F-FDG allows the clinical assessment of the therapeutic effects of photoimmunotherapy earlier than anatomic methods that rely on tumor size.