Photodynamic diagnosis of ovarian cancer using hexaminolaevulinate: a preclinical study

Abstract

The unfailing detection of micrometastases during surgery of patients suffering from ovarian cancer is mandatory for the optimal management of this disease. Thus, the present study aimed at determining the feasibility of detecting micrometastases in an ovarian cancer model using the intraperitoneal administration of the photosensitiser precursor hexaminolaevulinate (HAL). For this purpose, HAL was applied intraperitoneally at different concentrations (4 -12 mM) to immunocompetent Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. The tumours were visualised laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany), and the number of peritoneal micrometastases detected through HAL-induced photodiagnosis (PD) was compared to standard white light visualisation. Fluorescence spectra were recorded with an optical fibre-based spectrofluorometer and the fluorescence intensities were compared to the protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid under similar conditions. The number of metastases detected by the PD blue light mode was higher than when using standard white light abdominal inspection for all applied concentrations. Twice as many cancer lesions were detected by fluorescence than by white light inspection. The hexyl-ester derivative produced higher PpIX fluorescence than its parent substance aminolevulinic acid at the same concentration and application time. Fluorescence contrast between healthy and cancerous tissue was excellent for both compounds. To overcome poor diagnostic efficiency and to detect peritoneal ovarian carcinoma foci in the large surface area of the human peritoneal cavity, HAL fluorescence-based visualisation techniques may acquire importance in future and lead to a more correct staging of early ovarian cancer.

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates

“…Microendoscopy has taken microscopy to new depths in vivo using miniaturized optics (46), and this technology is emerging for "optical biopsy" of cancer (32,(47)(48)(49)(50)(51)(52)(53). Through the development of in vivo fluorescence microendoscopy with activatable immunoconjugates and automated image analysis algorithms (Fig.…”

Time‐dependent hexaminolaevulinate induced protoporphyrin IX distribution after topical application in patients with cervical intraepithelial neoplasia: A fluorescence microscopy study

“…Photodynamic therapy (PDT) and diagnosis (PDD) is emerging as an efficient but less aggressive alternative in the treatment and diagnosis of precancerous and cancerous lesions in hollow organs, such as Barrett's esophagus [3,4], upper aero-digestive tract [5,6], urinary bladder [7], or ovarian cancer [8]. The pharmacokinetics and localization of the photosensitizing drug play a key role in the mechanism of the PDT-induced damage.…”

“…The numerous photosensitizers currently under investigation include the hexyl-ester of 5-ALA (HAL), a precursor of protoporphyrin IX (PPIX) which given in excess can induce the accumulation of PPIXs in cells with high metabolic turnover [9][10][11]. We have chosen to use HAL, because it shows a homogenous distribution [12], better stability and better PPIXrelated fluorescence at lower doses than 5-ALA [8]. The more lipophilic derivative, HAL, is associated with an increase of the bioavailability and penetration depth through biological barriers resulting in up to 25-fold increase in PPIX fluorescence level compared to 5-ALA [13], permitting shorter times between administration and examination (for both PDD and PDT) while retaining the outstanding selectivity.…”

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring

“…Upon wavelength-specific activation of the PS, fluorescence emission for diagnostic imaging and cytotoxic species (through intersystem crossing to the triplet state) for tissue destruction can both be produced. Previous studies that used PS (ALA-induced protoporphyrin IX and/or hexaminolaevulinate) for OvCa imaging were successful in detecting significantly more lesions than white light imaging (Chan et al, 2002;Ludicke et al, 2003;Loning et al, 2004), with a ratio of fluorescence intensity of neoplastic to normal tissues of B4 (Chan et al, 2002;Ludicke et al, 2003). The average size of the optically biopsied metastatic lesions was 1.0 mm (range: 0.3 -2.5) compared with 1.5 mm (range: 0.5 -2.9) with white light illumination (Chan et al, 2002).…”