5-aminolevulinic-acid-hexyl-ester and Prostatic-Neoplasms

Urology is a preferential domain of endoscopy and as such an important research field for photodynamic procedures. An important milestone in the long-lasting and successful history of "photodynamics" in urology is the European approval of hexaminolevulinate (HAL, Hexvix) for fluorescence cystoscopy. All clinical studies carried out so far have demonstrated a significant increase in sensitivity of fluorescence versus standard cystoscopy for the detection of bladder cancer, especially concerning carcinoma in situ. The majority of the randomised, two-armed studies additionally show significantly reduced rates of residual tumour and recurrences. Tumor-selective fluorescence can also be observed in the kidney and prostate. Intraoperative fluorescence detection might thus simplify the achievement of high rates of R0 resections. Apart from the diagnostic potential of "photodynamics", also some possible therapeutic indications will be mentioned, including photodynamic therapy of bladder cancer and prostate cancer. Whereas initial clinical experience has been obtained for photodynamic therapy of bladder cancer, clinical studies for other indications are currently being designed. By providing an overview over methods and procedures as well as hitherto the available clinical results, we hope to provide reader with a basis for obtaining his/her own judgement.

Topics: Aminolevulinic Acid; Carcinoma in Situ; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cystoscopy; Dermatitis, Phototoxic; Fluorescence; Follow-Up Studies; Humans; Male; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Time Factors; Urinary Bladder Neoplasms

Prostate cancer is the second most common cancer in men and the second leading cause of male cancer deaths. The current blood test for detecting prostate cancers measures prostate-specific antigen. It has many limitations including a very high rate of false positives. Herein, prostate-specific membrane antigen (PSMA) based immunocapture and hexaminolevulinate (HAL) based photodetection are integrated into a new diagnostic device designed to selectively identify whole prostate cancer cells from voided urine with the aim of providing an accurate noninvasive alternative to current diagnosis methods. Prestained, prostate cancer cells spiked in urine samples at concentrations ranging from 1500 to 2000 cells/ml were captured with 89% sensitivity and 95% specificity. HAL, a cancer specific photosensitizer, was then used to circumvent the need for prestaining. Optimum HAL incubation conditions were identified (50 μM at 37 °C for 2 h) where the mean HAL-induced fluorescence intensity of LNCaP cells was three times that of healthy PNT2 cells, thus providing an independent way to discriminate captured cancer cells from background metabolites. Combining anti-PSMA immunocapture with HAL-induced fluorescent detection, 86% sensitivity and 88% selectivity were achieved, thereby proving the validity of the dual-method for the selective photospecific detection of prostate cancer cells.

Topics: Aminolevulinic Acid; Cell Count; Cell Line, Tumor; Cell Nucleus; Fluorescence; Humans; Male; Microfluidics; Photochemotherapy; Plasma Gases; Prostatic Neoplasms; Sensitivity and Specificity; Temperature; Time Factors

Six client-owned dogs with prostate carcinoma were treated with a combination of (1) partial subcapsular prostatectomy using an Nd:YAG laser, (2) intraoperative photodynamic therapy using a halogen broad band lamp after local administration of a photosensitiser, and (3) systemic treatment with meloxicam. Median survival time was 41days (range 10-68days), which compared negatively with previous reports of subtotal laser prostatectomy combined with topical interleukin-2 administration, and photodynamic therapy alone. Despite treatment, the disease progressed locally, causing signs of stranguria to recur, and in the form of distant metastases. The recurrence of clinical signs due to the primary tumour despite photodynamic therapy is probably largely explained by insufficient penetration of light into the tissue. Better results may be obtained using other light sources (e.g. laser) and alternative techniques of light delivery, such as fibres or catheters allowing interstitial diffusion of light.

Topics: Aminolevulinic Acid; Animals; Combined Modality Therapy; Dog Diseases; Dogs; Intraoperative Care; Male; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Prostatectomy; Prostatic Neoplasms