Biodistribution of photosensitizing agents

Abstract

1. 1. The features of neoplasia which predict for drug responsiveness are rapid growth and/or inefficient repair of damage, especially to DNA. 2. 2. PDT has the advantage of yielding responses regardless of the growth fraction of a tumor, and repair appears to play only a minor role. 3. 3. While an entirely different spectrum of tumors can be targeted with PDT, the perhaps unavoidable accompaniment is that a new set of rules for efficacy will need to be established. 4. 4. The selectivity of PDT is based on the need for irradiation which can be directed, along with the short tissue half-life of the cytotoxic product, singlet oxygen. Sensitizers which target specific cellular organelles could promote PDT efficacy, if in vitro data (Woodbum et at., 1992b Photochem. Photobiol. 55, 697–704) can be translated into clinical practice. 5. 5. It remains to be established whether total drug distribution to neoplastic tissues or concentration in specific sub-cellular sites is the more important factor. 6. 6. Questions relating to the role of biodistribution as a factor in efficacy of PDT sensitizers of photosensitizers remain to be explored. Just as the political cartographers are grappling with changes in territorial boundaries of known lands, we continue to clarify the rules relating to PDT boundaries. In this regard, it is clearly important for determinants of pharmacokinetics and biodistribution to be evaluated and understood. 7. 7. Once clinical reports on the “second generation” agents are published, we may get a better picture, although it is not unusual for clinical reports to raise more questions than they answer. 8. 8. It seems safe to conclude that there is nothing “magic” about HPD, and that additional efficacious photosensitizers for PDT can be produced. 9. 9. If we find that a wide variety of different structures are useful in the clinic, a likely conclusion is that there are multiple mechanisms of tumor localization. Since the nature of neoplasia is so diverse, this possibility should not be surprising. 10. 10. In view of the finding, cited above, that liposomes show about the same degree of tumor selectivity as does Photofrin, it may be feasible to target any efficient photosensitizer for neoplastic tissues by development of an appropriate delivery system.