Immunophotodynamic therapy: Current developments and future prospects

Photodynamic therapy (PDT) may offer an enhanced therapeutic index via one or more of the following modalities: a) preferential photosensitizer uptake by the target tissue, b) specific illumination of target tissue to excite the photosensitizer, c) strategic timing of light application to minimize toxicity to normal tissues, d) topical application of the photosensitizer restricted to the target tissue, infusion of the photosensitizer to the vasculature immediately upstream of the target, and intra-target administration. While each photosensitizer has inherent properties of biodistribution, it is generally accepted that few provide a significant therapeutic index and that the desired effect is far from universal with respect to turner types. Moreover, the optical properties of tumor and normal tissues vary dramatically and precision dosimetry remains an elusive goal in most clinical situations. Certain tumors, particularly those of the reticuloendothelial system, will usually be surrounded by normal stroma with greater concentrations of photosensitizer than are present in the tumor at a given post-administration interval, presenting a major obstacle to practical therapy. Deep-seated or large solid malignancies are not amenable to topical application of the photosensitizer and single tumor masses are frequently served by multiple arterial sources, rendering major dosimetric obstacles for photosensitizers administered via the upstream vasculature. One approach to specific photosensitizer delivery is via covalently bound immunoconjugates of photosensitizer and antibodies or antibody fragments to unique tumor markers. This approach is the subject of several clinical trials and provides encouragement for successful application in a wide variety of neoplastic diseases. In addition to therapeutic endpoints, this approach is capable of facilitating detection of subclinical lesions through the fluorescent properties of photosensitizers. (C) 1997 Wiley-Liss, Inc.