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

UNLABELLED

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.