Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer

Photodiagnosis Photodyn Ther. 2015 Jun;12(2):282-8. doi: 10.1016/j.pdpdt.2014.12.010. Epub 2015 Jan 13.

Abstract

Background: We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA).

Methods: Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated.

Results: The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively.

Conclusions: We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use.

Keywords: 5-Aminolevulinic acid; Photodynamic detection; Spectrophotometer; Urinary cytology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid / administration & dosage*
  • Aminolevulinic Acid / pharmacokinetics
  • Cell Line, Tumor
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / pharmacokinetics
  • Protoporphyrins / urine*
  • Sensitivity and Specificity
  • Spectrophotometry
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX