Differences in Therapeutic Efficacy in Pancreatic Cancer Between Interstitial and Superficial Light Delivery Strategies in Targeted Photo Therapy

Abstract

The purpose of this study was to determine if therapeutic efficacy of a Cetuximab based near-infrared (NIR) targeted photo therapy (TPT) was dependent on light delivery strategies. We examined the cytotoxic effects of TPT in a pancreatic cancer mouse model, when administered to tumors interstitially and superficially. A subcutaneous mouse model of pancreatic cancer using BXPC-3 - GFP cells was established in male athymic (nu/nu) mice. The mice received intravenous (IV) injection of Cetuximab-IR700DX, 24 hours prior to near-infrared light irradiation. Interstitial illumination was administered at a 400mW/cm fixed power output, at a light dose of 100 J/cm to half the mice and at 300 J/cm to the remaining mice. Superficial illumination was administered at a 150mw/cm2 fixed power density at a dose of 50 J/cm2 to half the mice, and at 250 J/cm2 to the other half. Cellular damage and decrease in cell viability was determined by the decrease in GFP fluorescence intensity levels in whole animal images and in relative intensity measurements. Interstitially administered TPT resulted in greater long-term permanent damage (72 hours post treatment) to tumor cells (0% recovery at low dose, and 11% recovery at high dose) compared to superficially administered TPT (1% recovery at low dose, and 44% recovery at high dose). While these results demonstrated that near-infrared targeted photo therapy efficacy was dependent on the type of light delivery strategy, overall, both superficial and interstitial Cet-IR700DX based near-infrared targeted photo therapy can effect significant long-term damage (less signal recovery) to pancreatic cancer cells in vivo at lower doses regimens, compared to higher dose regimens (higher signal recovery).