Colin Whitehurst

Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy.

Background A variety of protocols exist for the treatment of Bowen’s disease by photodynamic therapy (PDT) using topical 5‐aminolaevulinic acid (5‐ALA). Objective To determine the optimal wavelength (red or green light) for this treatment. Methods A randomized comparison study of ALA–PDT using red (630 ± 15 nm) or green (540 ± 15 nm) light in the treatment of Bowen’s disease. Results The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0·002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied. Conclusion Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen’s disease by topical ALA–PDT.

The biology of photodynamic therapy

The subcellular, cellular and tissue/tumour interactions with non-toxic photosensitizing chemicals plus non-thermal visible light (photodynamic therapy (PDT) are reviewed. The extent to which endothelium/vasculature is the primary target is discussed, and the biochemical opportunities for manipulating outcome highlighted. The nature of tumour destruction by PDT lends itself to imaging outcome by MRI and PET.

In situ comparison of 665 nm and 633 nm wavelength light penetration in the human prostate gland.

Abstract— The depth of treatment in photodynamic therapy (PDT) of tumors varies with the wavelength of light activating the photosensitizer. New generation photosensitizers that are excited at longer wavelengths have the potential for increasing treatment depths. Tin ethyl etiopurpurin (SnET2), a promising second‐generation photosensitizer is maximally activated at 665 nm, which may be significantly more penetrating than 633 nm light currently used with porphyrins in PDT. The penetration of 665 nm and 633 nm wavelength red light in the prostate gland was compared in 11 patients undergoing prostatic biopsies for suspected prostatic cancer. Interstitial optical fibers determined the light attenuation within the prostate gland. Of the 11 patients, 7 had dual wavelength and 4 had single wavelength studies. The mean attenuation coefficients, μeff, for 665 nm and 633 nm wavelength light were 0.32 ± 0.05 mm‐1 and 0.39 ± 0.05 mm‐1, respectively, showing a statistically significant difference (P= 0.0003). This represented a 22% increase in the mean penetration depth and at 10 mm from the delivery fiber there was 1.8 times as much 665 nm light fluence than 633 nm. The mean μeff at 665 nm for benign and malignant prostate tissue were similar (P = 0.42), however, there was significant interpatient variation (μeff ranging from 0.24 to 0.42 mm‐1) reflecting biological differences of therapeutic importance. The enhanced light fluence and penetration depth with 665 nm light should allow significantly larger volumes of prostatic tissue to be treated with SnET2‐mediated PDT.

Development of an alternative light source to lasers for photodynamic therapy: 3. clinical evaluation in the treatment of pre-malignant non-melanoma skin cancer

The efficacy of a prototype non-laser light source for photodynamic therapy was assessed in clinical practice in the treatment of Bowens disease and actinic keratoses. The light source, incorporating a 300 W short arc plasma discharge, was adjusted by appropriate filters to produce a bandwidth of 630±15 nm. Topical 5-aminolaevulinic acid was applied 4 h before irradiation to permit production within the lesion of the active photosensitizer, protoporphyrin IX. Individual lesions received 94–156 J cm−2. Twenty lesions of Bowens disease and four actinic keratoses were treated in 12 patients. Patients were reviewed at monthly intervals and treatment repeated if residual disease was present. Clearance was achieved with a single treatment in 15 lesions and in all of the remaining nine lesions after a second treatment. The treatment was well tolerated, with pain absent or mild during treatment in 22 lesions, with only one lesion requiring local anaesthesia. Over the 10 days following treatment, no pain was associated with 21 treated lesions. During a 12 month follow-up period, two Bowens disease lesions recurred. The overall complete response rate was 92%. Scarring was evident following PDT in only three lesions. Photodynamic therapy using this portable non-laser light source appears to be an effective and well-tolerated treatment for Bowens disease and actinic keratoses.

Photodynamic therapy for superficial bladder cancer under local anaesthetic.

Objectives To evaluate the use of local anaesthesia (LA) in 5‐aminolaevulinic acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma (TCC) of the bladder, and to provide further toxicity and tolerability data on this new method within the context of a phase 1 trial.

Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumours

Objectives To assess (i) the optical properties and depth of penetration of varying wavelengths of light in ex‐vivo human bladder tissue, using specimens of normal bladder wall, transitional cell carcinoma (TCC) and bladder tissue after exposure to ionizing radiation; and (ii) to estimate the depth of bladder wall containing cancer that could potentially be treated with intravesical photodynamic therapy (PDT), assuming satisfactory tissue levels of photosensitizer.

An interstitial light assembly for photodynamic therapy in prostatic carcinoma

 To develop an interstitial laser light delivery system using multiple optical fibres for photodynamic therapy (PDT) in the treatment of prostate cancer.

Development of an alternative light source to lasers for photodynamic therapy: 2. Comparative in vivo tumour response characteristics

The performance of a low cost, table-top/portable light source was tested against an argon ion pumped dye laser for in vivo photodynamic therapy (PDT). The prototype delivers up to 1 W via a 4 mm flexible lightguide within a 30 nm bandwidth centred at any wavelength from 300 nm to 1200 nm at fluence rates of up to 8 W cm−2. An in situ bioassay using regrowth delay of tumour T50/80 was used to quantify the relative efficacy of the prototype with a laser. The tumours were sensitized with haematoporphyrin derivative (HpD) and externally irradiated. There was no significant difference in the response of the tumour to treatment between the two light sources (p = 0.69). Mean growth delays ranged from 2 days (light dose 10 J cm−2) to 20 days (light dose 100 J cm−2). The estimate for the difference in means (laser minus prototype growth delay) was only 0.66 days and was not statistically significant. This in vivo study demonstrates that the prototype is equivalent to a laser in PDT effect. The device has low capital/running cost, is simple to use and is one of the most powerful, spectrally efficient non-laser PDT sources available.

PHOTODYNAMIC THERAPY (PDT) OF GASTROINTESTINAL TUMOURS : A NEW LIGHT DELIVERY SYSTEM

Abstract. The Paterson lamp is a convenient, low cost, portable, alternative light source to lasers for photodynamic therapy (PDT). A multiwavelength capability enables the clinician to vary the photosensitiser used. The Paterson lamp has been applied in the field of dermatology using a liquid light guide with distal optics for surface application. We now describe distal optics suitable for use with this light guide for intraluminal applications in the oesophagus and colorectum.The geometry of the site (oesophagus and colorectum) requires distal optics such as a cylindrical diffuser or a side-fire diffuser. We have designed new probes that diffuse light radially from the guide axis (cylindrical diffusion). The tips have a frosted glass surface that scatters and effectively couples light radially into the tissue. An acrylic spacer is placed over the diffuser to position the tissue at a constant diameter from the probe. This is held in position by a silicone sheath placed over the distal one metre. For use in the oesophagus, a channel, to facilitate intubation over a guide wire, is included. The diameter of the entire probe is 8.4 mm and the power output can be adjusted from 0–500 mW. Pilot PDT of tubulovillous adenomas of the rectum and Barretts oesophagus using this light delivery system is currently underway and has shown good early response in the treated area.

OPTIMIZATION OF MULTIFIBER LIGHT DELIVERY FOR THE PHOTODYNAMIC THERAPY OF LOCALIZED PROSTATE CANCER

The understanding of light distribution within the target organ is essential in ensuring efficacy and safety in photodynamic therapy (PDT). A computer simulator of light distribution in prostatic tissue was employed for optimizing dosimetry for PDT in localized prostatic cancer. The program was based on empirically determined light distributions and optical constants and an assumed Ruence rate differential from fiber source to necrosis periphery. The diffusion theory approximation to the Boltzmann transport equation was the applicable formulation relevant to prostatic tissue, which has a high albedo with forward‐scattering characteristics. Solving this equation of diffusive transfer for the appropriate fiber geometry yielded the energy fluence distributions for cleaved fiber and cylindrical diffuser light delivery. These distributions, confirmed by our measurements, show a l/r and l/r dependency (r = distance from light source) of the fluence ø(r) for the cleaved fiber and diffuser, respectively. This manifests itself by the tighter spacing of energy fluence isodoses in the case of the cleaved fiber. It was predicted that for a typical PDT regime a single interstitially placed cleaved fiber would treat 0.05–0.72 cm3, Four parallel fibers improve the uniformity of light distribution and treatment volume, and an interfiber separation of 12 mm would be necessary to provide optimal overlap of PDT necrosis, treating 0.26–3.6 cm3. The cylindrical diffuser, however, could treat larger volumes, and it was predicted that four 3 cm long diffusers at an optimal separation of 25 mm would treat 25–88 cm3 of prostatic tissue.