History of Photodynamic Therapy (PDT)

In 1900 Oscar Raab, a German medical student, discovered that the combination of the chemical acridine acridine and light at certain wavelengths was lethal to Paramecium caudatum, a certain infusoria species.[1]

Three years later, H. von Tappeiner and A. Jesionek treated skin tumours with eosin and white light[2]. In 1904 they described their observation as “photodynamic action”.

Seven years later, W. Hausmann discovered the outstanding photodynamic effect of hematoporphyrin, an iron-deficient derivative of hem. He induced cell death with hematoporphyrin and light in red blood cells and paramecium, in addition, reported skin reactions in mice after treatment with this combination [3].

F. Meyer-Betz, another German scientist, was the first to inject 200 mg of hematoporphyrin into his own vein in 1912. He experienced pain and swelling of the skin after light exposure[4].

In 1942, Auler and Banzer discovered tumour selectivity of porphyrins by porphyrin fluorescence in tumour tissue of rats after systemic application.

Then, in 1955 Samuel Schwartz developed hematoporphyrin derivative (HPD) by acetylation and reduction of hematoporphyrin[5], which was found to be twice as phototoxic as hematoporphyrin .

R. Lipson and E. J. Baldes at the Mayo Clinic were the first to use this new compound for photodetection of tumours in 1960 [6]. It took another twelve years until I. Diamond was able to show the phototoxicity of HPD against gliomas in vivo and in vitro [7].

In 1961, T. Dougherty treated the first patients with skin tumours [8] and J.F. Kelly treated the first patients with bladder cancer successfully [9]. Other groups continued and extended their investigations [10].

Following this success, Y. Hayata demonstrated the effectiveness of PDT in obstructing lung tumours [11], which was confirmed by other groups who treated also early-stage lung cancer [12]. In 1984, J.S. McCaughan extended the procedure to patients with oesophageal cancer[13].

Patients with gynaecological tumours [14], including breast cancer [15], intraocular tumours [16], brain tumours, head and neck tumours [17], oral cavity tumours [18], intraperitoneal tumours [19], prostate cancer [20], were subsequently treated with PDT.

Finally, the use of PDT has been extended to non-oncologic indications, such as Barrett’s esophagus [21], laryngeal papillomatosis [22], actinic keratosis [23], and age-related macular degeneration [24].

In 1993, the purified HPD Photofrin ® (porfimer sodium) was first officially approved in Canada for the treatment of bladder cancer, followed by the U.S. Food and Drug Administration (FDA) and numerous other health agencies throughout the world. Then, FDA extended the license to obstructive oesophageal cancer and Barrett’s esophagus, in addition to early stage and advanced lung cancer.

In August 2002, PhotosanR, another HPD derivative has gained approval in Europe. In the meantime, LevulanR (5-aminolevulanic acid; ALA) has been approved for the treatment of actinic keratosis and Vertiporfin (benzoporphyrin derivative; BPD) for agerelated macular degeneration in the USA. Certain other socalled “second generation photosensitizers” as discussed forward are now under way for approval in the USA and Europe.