Experimental photoimmunotherapy of hepatic metastases of colorectal cancerwith a 17.1A chlorin(e6) immunoconjugate

Photoimmunotherapy (using a monoclonal antibody-targeted photosensitizer an d red light) may be a strategy to overcome the Limitations inherent in phot odynamic therapy of liver tumors. The aims of this study were (a) to test t he efficacy of selective treatment of hepatic metastases of colorectal canc er in an orthotopic murine xenograft using the murine monoclonal antibody 1 7.1A conjugated to the photosensitizer chlorin(e6), and (b) to compare the tumor response after the same light dose was delivered at two different flu ence rates. Based on previous biodistribution studies that had shown that t he photoimmunoconjugate with a polyanionic charge had both a higher absolut e tumor chlorin(e6) content and a greater tumor:normal liver ratio than tho se obtained with a photoimmunoconjugate bearing a polycationic charge, mice were treated 3 h after i.v. injection of the polyanionic 17.1A chlorin(e6) conjugate or unconjugated photosensitizer. Red light was delivered into th e liver tumor by an interstitial fiber, and tumor response end points were total tumor weight in the short term and survival in the long term. There w as a highly significant reduction (<20% of controls; P = 0.0035) in the wei ght of the tumors in the mice treated with photoimmunotherapy, and the medi an survival increased from 62.5 to 102 days (P = 0.015). Photodynamic thera py with free chlorin(e6) produced a smaller decrease in tumor weight and a smaller extension of survival, neither of which were statistically signific ant. A comparison of photoimmunotherapy with 10 J of light delivered at 30 or 300 mW showed that the higher fluence rate prolonged survival significan tly more than the Lower fluence rate. This may have been because the high f luence rate gave a contribution of laser-induced hyperthermia to the photod amage. Correlation studies showed that the amount of normal liver remaining at necropsy correlated best with survival. Photoimmunotherapy shows effica cy in destroying liver tumors, and future studies should maximize selectivi ty to minimize the destruction of normal liver.