Photodetection with 5-Aminolevulinic Acid–induced Protoporphyrin IX in the Rat Abdominal Cavity: Drug-dose–dependent Fluorescence Kinetics¶

Abstract In 75% of cases, ovarian carcinoma has already metastasized in the abdominal cavity at the time of diagnosis. For determination of the necessity for a supplementary therapy, in addition to surgical resection, it is important to localize and stage microscopical intraperitoneal metastases of the tumor. Intraperitoneal photodetection of tumor metastases is based on preferential tumor distribution of a fluorescent tumor marker. The time-dependent differences in drug concentration between tumor and normal (T/N) tissues can be used to visualize small tumors. We performed fluorescence measurements on abdominal organs and tumor in the peritoneal cavity of rats. 5-Aminolevulinic acid (ALA)–induced protoporphyrin IX (PpIX) was used as the fluorescent marker. Three different drug doses (100, 25 and 5 mg/kg) were used and PpIX fluorescence profiles were followed up to 24 h after intravenous administration. Maximum T/N ratios were found 2–3 h after administration of ALA with all drug doses. A significant T/N tissue contrast was obtained for all abdominal organs tested after administration of 5 mg/kg.

[1]  J. Kennedy,et al.  Fluorescence and photosensitization of experimental endometriosis in the rat after systemic 5-aminolevulinic acid administration: a potential new approach to the diagnosis and treatment of endometriosis. , 2011, American journal of obstetrics and gynecology.

[2]  F. Stewart,et al.  White-light toxicity, resulting from systemically administered 5-aminolevulinic acid, under normal operating conditions. , 1999, Journal of photochemistry and photobiology. B, Biology.

[3]  R. van Hillegersberg,et al.  Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus. , 1998, British Journal of Cancer.

[4]  J. Thigpen,et al.  High-dose chemotherapy in ovarian carcinoma. , 1999, Seminars in oncology.

[5]  J. Kennedy,et al.  Detection of Early Stages of Carcinogenesis in Adenomas of Murine Lung by 5‐Aminolevulinic Acid‐Induced Protoporphyrin IX Fluorescence , 1996, Photochemistry and photobiology.

[6]  A B Houtsmuller,et al.  5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration. , 1998, Journal of photochemistry and photobiology. B, Biology.

[7]  R Baumgartner,et al.  Pharmacokinetics of 5-aminolevulinic-acid-induced porphyrins in tumour-bearing mice. , 1996, Journal of photochemistry and photobiology. B, Biology.

[8]  M Korell,et al.  Pharmacokinetics and selectivity of aminolevulinic acid–induced porphyrin synthesis in patients with cervical intra‐epithelial neoplasia , 1998, International journal of cancer.

[9]  M. Parmar,et al.  Randomised trials in ovarian cancer: trial design considerations. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  R Baumgartner,et al.  Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid. , 1994, Urology.

[11]  Martin Kriegmair,et al.  CELLULAR FLUORESCENCE OF THE ENDOGENOUS PHOTOSENSITIZER PROTOPORPHYRIN IX FOLLOWING EXPOSURE TO 5‐AMINOLEVULINIC ACID , 1995, Photochemistry and photobiology.

[12]  H Stepp,et al.  Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. , 1996, The Journal of urology.

[13]  G. Kuhnle,et al.  In vivo kinetics and spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster. , 1994, British Journal of Cancer.

[14]  N. Brown,et al.  Kinetics of endogenous protoporphyrin IX induction by aminolevulinic acid: preliminary studies in the bladder. , 1994, The Journal of urology.

[15]  G. Thompson,et al.  Tissue uptake of δ-aminolaevulinic acid , 1975 .

[16]  R. Veenhuizen,et al.  Intraperitoneal photodynamic therapy in the rat: Comparison of toxicity profiles for photofrin and mTHPC , 1994, International journal of cancer.

[17]  Massoud Motamedi,et al.  Spectroscopic detection of oral and skin tissue transformation in a model for squamous cell carcinoma: autofluorescence versus systemic aminolevulinic acid-induced fluorescence , 1996 .

[18]  A. E. Saarnak Evaluation of fluorescence measurement techniques for tumour detection in vivo , 1999 .

[19]  R. van Hillegersberg,et al.  Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. , 1992, Gastroenterology.

[20]  Leslie Anne Sabiniano,et al.  In vivo detection of metastatic ovarian cancer by means of 5-aminolevulinic acid-induced fluorescence in a rat model. , 1998, The Journal of the American Association of Gynecologic Laparoscopists.

[21]  H. Sterenborg,et al.  Quantification of the hematoporphyrin derivative by fluorescence measurementusing dual-wavelength excitation anddual-wavelength detection. , 1993, Applied optics.

[22]  H Stepp,et al.  Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood. , 1997, Journal of photochemistry and photobiology. B, Biology.