history of photodetection and photodynamic therapy, The

Photochemistry and Photobiology, Nov 2001 by Ackroyd, Roger, Kelty, Clive, Brown, Nicola, Reed, Malcolm

The History of Photodetection and Photodynamic Therapy

ABSTRACT

Light has been employed in the treatment of disease since antiquity. Many ancient civilizations utilized phototherapy, but it was not until early last century that this form of therapy reappeared. Following the scientific discoveries by early pioneers such as Finsen, Raab and Von Tappeiner, the combination of light and drug administration led to the emergence of photochemotherapy as a therapeutic tool. The isolation of porphyrins and the subsequent discovery of their tumor-localizing properties and phototoxic effects on tumor tissue led to the development of modern photodetection (PD) and photodynamic therapy (PDT). This review traces the origins and development of PD and PDT from antiquity to the present day.

INTRODUCTION

Light has been employed in the treatment of disease since antiquity. However, it is only relatively recently that it has been used to any significant degree in medicine and surgery. In the latter part of the twentieth century it has been used in many different forms, including phototherapy for neonatal jaundice, the combination of psoralen molecules and ultraviolet A light (PUVA) in dermatology, photodynamic therapy (PDT) and photodetection (PD) which are the subject of this article.

PDT is a promising treatment for cancer and other nonmalignant conditions, which involves the administration of a photosensitizing agent (usually a porphyrin-based compound) followed by exposure of the tissue to visible nonthermal light (400-760 nm). When the photosensitizer is illuminated with light of the appropriate wavelength, the molecule is excited. This produces a series of molecular energy transfers leading to the liberation of singlet oxygen, a highly reactive and cytotoxic species, resulting in cell death (1). Photosensitizers are often taken up by malignant or dysplastic tissues with some selectivity, and light delivery can be targeted to the appropriate tissue (2). The combination of drug uptake in malignant tissues and selective light delivery has the potential to provide an effective tumor therapy with efficient cytotoxicity and limited damage to the surrounding normal tissue (3).

However, although the concept of PDT has been known for about 100 years, it is only since World War II that it has become familiar to the English-speaking world. Much of the pioneering work was performed in Europe and, therefore, the early literature was published in German, French and Danish texts. In view of this, the origins of PDT are perhaps not widely known, and with the exception of the occasional review (4) the literature regarding the history of PDT is rather sparse. In this review we aim to document the history and development of phototherapy, PD and PDT from antiquity to the present day, highlighting the major milestones and guiding the reader to further reviews detailing all aspects of the current status of PDT in depth.

PHOTOTHERAPY AND

PHOTOCHEMOTHERAPY

The use of light as a therapeutic agent can be traced back over thousands of years. It was used in ancient Egypt, India and China to treat skin diseases, such as psoriasis, vitiligo and cancer, as well as rickets and even psychosis (5,6). The ancient Greeks employed whole-body sun exposure or heliotherapy in the treatment of disease, and lying nude in the sun was a popular pastime. The famous Greek physician, Herodotus, who was regarded as the father of heliotherapy, emphasized the importance of sun exposure for the restoration of health. However, it was not until recently that the therapeutic effects of sunlight were widely used in medicine.

In the eighteenth and nineteenth centuries in France, sunlight was used in the treatment of various conditions, including tuberculosis, rickets, scurvy, rheumatism, paralysis, edema and muscle weakness (7). Phototherapy was further developed by the Danish physician, Niels Finsen, who at the turn of the last century described the successful treatment of smallpox using red light, which prevented suppuration of the pustules (8). He then went on to use ultraviolet light to treat cutaneous tuberculosis and developed the use of carbon arc phototherapy in the treatment of this condition for which he was awarded a Nobel Prize in 1903.

Phototherapy describes the use of light in the treatment of disease, photochemotherapy, on the other hand, involves a combination of the administration of a photosensitizing agent followed by the action of light on tissues in which the agent is localised. This form of therapy also dates back over 3000 years when the Indians used psoralens in the treatment of vitiligo, and in the twelfth century the Egyptians employed different psoralens in the treatment of leucoderma (9). More recently, in 1834, Kalbrunner isolated the chemical bergapten or 5-methoxypsoralen from bergamot oil but did not use it in any therapeutic application. It was not until the 1970s that psoralens, activated by ultraviolet A light (PUVA therapy), were used clinically in the treatment of psoriasis and more recently for vitiligo and in immunotherapy (6).