Chemistry Reference
In-Depth Information
future of transition metal polyazine complexes as PDT agents. Polyazine metal
complexes have properties that make them a promising class of future PDT agents,
which will be highlighted herein.
Photodynamic therapy is a modern treatment that uses light and a chromo-
phoric molecule (PDT agent) to locally photosensitize tissues and to selectively kill
targeted cells. PDT has potential applications in the treatment of localized tumours
and intravascular diseases. Following administration of the PDT agent, the lesion of
interest is irradiated with visible or near-infrared (NIR) light. Complicated photo-
chemical reactions ensue, inducing apoptosis and/or necrosis, hopefully resulting in
ablation of the lesion. PDT holds particular promise in the treatment of cancer as
it tends to have fewer systemic toxic effects commonly associated with traditional
radiation and chemotherapies.
8.1.1 Cancer
Cancer is a disease caused by uncontrolled growth of abnormal cells, impacting the
functioning of bodily tissues and organs. A mass of cancer cells, also known as a
tumour or lesion, has many stages of growth. Initial mass formation is typifi ed by
rapid growth concomitant with poor vascularization within the lesion. Continued
rapid growth results in the centre of the mass becoming hypoxic and undergoing
necrosis. Abnormal cells may break off of the primary tumour and migrate
throughout the body in a process called metastasis. Current cancer treatments are
relatively crude, having severe side effects. These include surgery (invasive, risk
of infection, complications), chemotherapy (poor cytospecifi city/ selectivity, sys-
temic toxicity effects) and radiation therapy (radiation sickness, increased risk of
secondary tumours). Ideal treatments of cancer could be used in the ablation of
lesions without the side effects which greatly impact the quality of life of the
patient.
8.1.2 A Brief History of PDT and Current Clinical Treatments
Photodynamic therapy has been expanding as a treatment of a wide range of local-
ized maladies. Photodynamic action was fi rst described in 1900 by Oscar Raab.
12
In
1905 von Tappeiner and Jesionek reported the fi rst successful clinical use of PDT
to treat basal cell carcinoma with a topical application of eosin red and light.
13
PDT
studies were largely abandoned until the late 1970s, when animal trials using hemat-
oporphyrin derivatives gave promising results in the treatment of animal cancers.
Approval of the hematoporphyrin derivative, Photofi n
®
, for use in PDT did not
occur in the US until 1995 (Figure 8.1).
14
Within the US, 5-aminolevulinic acid
(Levulan
®
) is the only other approved chemical for use in PDT, gaining approval in
2000. Levulan
®
acts as a prodrug, enhancing porphyrin anabolism. The European
Union, Norway and Iceland have approved Foscan
®
, a chlorin (chlorophyll deriva-
tive), for the treatment of head and neck cancers. At the time of writing there were
three chromophores in current clinical trials: metoxifi n lutetium (Lutex), tin ethyl
