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The porphyrin handbook - Kadish K.M.

Kadish K.M. The porphyrin handbook - Academic press, 2000. - 368 p.
Download (direct link): kadishsmishgulilard2000.djvu
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the tumor
itself appear to be much less pertinent
Lu-Tex 1. Strong absorption at 732nm 1. Pain
associated in the skin during Pharmacyclics
(expanded porphyrin) 2. No skin phototoxicity light
treatment California, USA
3. Effective photosensitizers 2. Multi-
step synthesis
ALA 1. Available as a chemical 1. Pain
associated during PDT DUSA, NJ
(Protoporphyrin IX- 2. No skin phototoxicity treatment
precursor) 3. Easy to formulate 2. Limited
depth of tumor necrosis (approximately 1 mm)
HPPH 1. Easy to synthesize 1. Limited
clinical data RPCI, Buffalo
(Chlorophyll a 2. Easy to formulate
analogue) 3. Strong absorption (660 nm)
4. Very effective photosensitizer
5. No skin phototoxicity
Pandey and Zheng
Scheme 96. New photosensitizers under clinical investigation.
102b H2(m -THPC)
472b H2(Pc4)
89 SnEt2
Rl = H, R2 = CH3 or
R, = CH3, R2 = H
R = -
18a NPe6
subcutaneous tissue received 44 treatments in a phase-I clinical
trial.365 The clinical protocol included a drug dose of 0.6-7.2mg/kg, a
light dose of 150J/cm2, and a drug-light interval of 3 hours. The
selectivity of Lu(Tex) for cancers was demonstrated by specific 750-nm
fluorescence emission from tumor and not normal skin. Of 163 lesions
evaluable to date, 29% had a complete response and 17% had a partial
response. Of 74 breast cancer lesions, 42% underwent a complete response,
and 23% underwent a partial response. Phase-II trials for locally
recurrent breast cancer are ongoing.
The 2-(l-hexyloxyethyl) 2-devinyl-pyropheophorbide a (HPPH) named
Photoclor, a new second-generation photosensitizer developed by Pandey
and Dougherty,366 is also entering a phase-I clinical trial for the
treatment of advanced esophageal tumors. Results to date from four
patients with esophageal cancer are encouraging
with complete tumor response and no significant cutaneous skin
phototoxicity. Finally, the tetrasulfonated zinc phthalocyanine Zn(Pc4)
made by Kenney and coworkers is waiting FDA approval for phase I/II human
clinical trials.
The advantages and disadvantages of selected photosensitizers are briefly
summarized in Table 1.
XV. Conclusions
The worldwide approval of Photofrin for the treatment of various types of
cancers has created enormous interest
43/Porphyrins as Photosensitizers in Photodynamic Therapy
among physicians, chemists, biologists and physicists. This is now one of
the accepted modalities for the treatment of cancer. In recent years a
number of pharmaceutical companies such as QLT Pharmaceuticals,
Vancouver, British Columbia; PDT Inc., Santa Barbara, California; Scotia
Pharmaceuticals, United Kingdom; Ciba Vision, New Jersey; Sanofi
Pharmaceuticals, North Carolina; Pharmacia and Upjohn, Sweden; DUSA, New
Jersey; and Pharmacyclics, California, have shown major interest in
developing photodynamic therapy. In addition to its use for cancer
treatment, PDT has also shown a potential for applications in other
areas: treatment of age-related macular degeneration (AMD), psoriasis,
bone marrow purging, arthritis and purification of blood infected with
various viruses, including HIV. At present, all the photosensitizers in
clinical trials are based on tetrapyrroles (porphyrins, chlorins,
bacteriochlorins and phthalocyanines), and it seems that porphyrins in
general will show continued interest in the exciting area of photodynamic
The future of PDT will depend on those photosensitizers which are
effective, have long-wavelength absorptions in the near infrared regions,
and show minimal skin phototoxicity. To facilitate drug development, it
is necessary to identify the targets. The initial studies with HPPH and
other photosensitizers have suggested that the mitochondria and lysosomes
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