History of PDT

PDT In Ancient Medicine

The earliest recorded treatments that exploited a photosensitizer and a light source, in this case sunlight, for medical effect can be found in ancient Egyptian and Indian sources. Annals over 3000 years old report the use of topically applied vegetable and plant substances to produce photoreactions in skin and cause a repigmentation of depigimented skin lesions, as seen with vitilago and leukoderma.

The photosensitizing agents used in these ancient therapies have been characterised with modern science as belonging to the psoralen family of chemicals. Psoralens are still in use today in PDT regimes to treat a variety of skin conditions, including vitiligo, psoriasis, neurodermitis, eczema, cutaneous T-cell lymphoma and lichen ruber planus.

20th Century Development of PDT

The first detailed scientific evidence that agents, photosensitive synthetic dyes, in combination with a light source and oxygen could have potential therapeutic effect was made at the turn of the 20th century in the laboratory of von Tappeiner in Munich, Germany. Historically this was a time when Germany was leading the world in the industrial synthesis of dyes.

While studying the effects of acridine on paramecia cultures, Oscar Raab, a student of von Tappeiner observed a toxic effect. With the discovery of photodynamic effects, von Tappeiner and colleagues went on to perform the first PDT trial in patients with skin carcinoma using the photosensitizer, eosin. Out of 6 patients with a facial basal cell carcinoma, treated with a 1% eosin solution and a long-term exposure either to sunlight or to arc-lamp light, 4 patients showed total tumour resolution and a relapse-free period of 12 months.

It was only much later, when Thomas Dougherty and co-workers at Roswell Park Cancer Institute, Buffalo NY, clinically tested PDT again. In 1978, they published striking results in which they treated 113 cutaneous or subcutaneous malignant tumors and observed a total or partial resolution of 111 tumors. In this impressive research, Dougherty also pioneered the use of fibre optic cables to deliver laser light directly to the site of the tumour and regulate the light dose. Following this, Dougherty went on to become a highly visible advocate and educator of PDT, sharing his research with other clinics in the USA and overseas. In 1986 he formed the International Photodynamic Association.

Photofrin was the first PDT agent approved for clinical use in 1993 to treat a form of bladder cancer in Canada. Over the next decade, PDT received wider international attention and grew in their clinical use, and lead to the first PDT treatments to receive U.S. Food and Drug Administration approval.

Modern Development of PDT

Of all the nations beginning to use PDT in the late 20th Century, the Russians were the quickest to advance its use clinically and to make many developments. One early Russian development was the clinical testing of Photochem from February 1992 to 1996. A pronounced therapeutic effect was observed in 91 percent of the 1500 patients that underwent PDT using Photochem, with 62 percent having a total tumor resolution. Of the remaining patients, a further 29 percent had a partial tumor resolution, where the tumour at least halved in size. In those patients that had been diagnosed early, 92 percent of the patients showed complete resolution of the tumour.

From 1994 to 2001, Russia launched clinical trials of even more promising photosensitizers. Most notably, these new photosensitizers exhibited a higher photodynamic activity in the red region of light, making them more suitable to treat deep tumors. The photosensitizers also had a faster clearance time from normal tissues, making them more selective for tumour cells. At present, PDT is still being developed within Russia. Most notably, in the application of PDT as an antimicrobial treatment for drug resistant MRSA and TB infections.

Today, the overall the beneficial effect of PDT has been witnessed across the world, with countless lives saved. The PanAmerican Photodynamic Association was established with the goal of galvanizing the basic science and clinical expertise of PDT in the Americas and enabling the clinical field of PDT to move forward.

To read more about the history of PDT, please visit Wikipedia.