Objective  To determine the depth of tissue destruction and the minimum light dose required for necrosis in interstitial photodynamic therapy (PDT), as a prerequisite for the investigational therapy of patients. Materials and methods  Seven adult beagle dogs were given 2 mg/kg of the photosensitizer Photofrin™ intravenously and two controls received none. After 24 h, 450 J/cm of 630 nm wavelength laser light was delivered interstitially to the prostate via a 2 cm long diffuser fibre. Seven single‐fibre treatments were performed in five sensitized dogs and two single‐fibre treatments in the controls. The two remaining sensitized dogs had two fibres placed 10 mm apart within the prostate to determine the coalescence of PDT lesions. The penetration depth of light was measured in all prostates, and after PDT the extent of necrosis was assessed histologically. Results  The mean (standard deviation, sd) radius of PDT destruction around each diffuser was 5.3 (1.4) mm and PDT lesions overlapped in prostates treated with two fibres placed 10 mm apart. There was no observable tissue damage in the controls. The mean (sd) minimum light dose required for PDT necrosis was 84 (64) J/cm2 . Differences among animals in the light penetration depth were small, with a mean of 2.14 (0.2) mm, and did not correlate with the depth of necrosis (P=0.07). Bleeding around the optical diffuser fibre impeded light penetration. Conclusion  Interstitial PDT in the canine prostate using Photofrin™ produced modest volumes of tissue necrosis. The minimum light dose required to induce necrosis was variable because bleeding was unpredictable in relation to the optical fibre.

We are investigating the feasibility of photodynamic therapy in the treatment of localised prostatic cancer. Of major importance in this form of treatment is the extent to which light penetrates the target organ; hence, our interest in the optical properties of the human prostate gland. We obtained three whole prostates from autopsies of patients who died of non-urological causes. Red light was launched interstitially and detector fibres measured light intensity as a function of distance from the delivery fibre end. The optical constants derived from the three prostates were almost identical and indicated that light was predominantly scattered rather than absorbed (mean absorption and scattering coefficients 0.07 +/- 0.02 mm.-1 and 0.86 +/- 0.05 mm.-1 respectively). In a comparison of the tissue penetration by four different wavelengths, 633 nm red light was found to be transmitted best. Light propagation in the heavily absorbing tissue of the human liver was 4.3 times poorer than in the prostate. Such a combination of low absorption and high scattering characteristics in prostatic tissue would enhance the effectiveness of PDT. The optical constants derived will enable "light treatment planning" in patients with prostatic cancer.

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.

The extent of laser light diffusion within prostatic tumor is of major importance in the treatment of localized prostatic cancer with photodynamic therapy (PDT). The penetration of 633 nm. wavelength red light was studied in eleven patients with suspected prostatic cancer using a novel method suitable for in situ measurements. Light delivery and detector fiber, placed interstitially within the gland, determined light attenuation at different interfiber separations. Of 11 patients, 10 had bilateral and 1 had single lobe studies. The mean +/- the standard error of the mean attenuation coefficients (sigma eff) for benign and malignant prostate tissue were 0.35 +/- 0.02 mm-1 and 0.36 +/- 0.02 mm-1, respectively, indicating similar optical densities (p = .58). Patients with bilateral lobe involvement showed little intraglandular variation in sigma eff (p = 0.23). However, there was interpatient variation (sigma eff = 0.28 to 0.48 mm-1) reflecting biological differences which, though therapeutically important, were not statistically significant (p = 0.057). This study showed that treatment requires individualization and predicted that 4 cylindrical diffusers are expected to destroy 25 ml. of prostatic tumor with PDT.