Early uses and studies of photosensitizers involved a class of compounds known as porphyrins. Early research on porphyrins was conducted by Meyer-Betz in 1913. Porphyrin is a component of heme found in hemoglobin, myglobin and other proteins of plants and animals. The porphyrin’s basic ring structure (Fig. 4) has several positions that are susceptible to substitution allowing for vast complexity and diversity of porhyrin based structures. Many porphyrin based structures are in clinical trials or currently being used (Fig. 3).

There exist two classifications of photosensitizers; Anionic Lipophilic and Cationic photosensitizers. These two classes differ only by there means of eliminating neoplastic tissue. Anionic Lipophilic (AL) photosensitizers are the most widely used and have had the majority of clinical studies. AL photosensitizers concentrate on the destruction of Tumor vasculature. In contrast Cationic photosensitizers focus on the cancer cells directly thus making them more efficient.

The older more commonly used photosensitizers are called the first generation photosensitizers and include hematoporphyrin derivative (HPD) and porifimer sodium (Photofrin®).(2) First generation photosensitizers tend to have prolonged, increased skin sensitivity as a side effect. The second generation photosensitizers have been constructed to better their localizing ability using a shorter period of time. Benzoporphyrin derivative monoacid (BPD-MA) is an example of the newer photosensitizers currently in clinical trials.

Besides advancements in photosensitizer efficiency the methods by which they are administered have advanced substantially. Intially presythesized sensitizers were administered followed by a short delay to allow for localization of the photosensitizer.(2) the patient was treated with PDT and again another delay was required to allow for all photosensitizers to be cleared from normal tissue. Recently a new approach has been of particular interest “instead of a photosensitizer being administered in a synthetic form, a precursor is administered, and the photosensitizer is synthesized in situ in tumors.”(1) The advantage of this method is the decreased delay before PDT can ensue and the increased precision of neoplastic tissue targeting. An example of a current precursor is aminolevulinic acid (ALA) which is a naturally occurring precursor for heme production.