Kidney-preserving tumour resection in renal cell carcinoma with photodynamic detection by 5-aminolaevulinic acid: preclinical and preliminary clinical results.

Abstract

To identify the outer border of a renal cell carcinoma (RCC) during a kidney-preserving tumour resection by photodynamically detecting RCC after the exogenous administration of 5-aminolaevulinic acid (ALA) in an animal model and in humans. Human RCC was xenotransplanted subcutaneously and orthotopically into the kidneys of nude mice. ALA was then administered orally or intravenously (100-400 mg/kg body weight). The tumours were removed and examined macroscopically and microscopically for fluorescence, and the concentrations of protoporphyrin IX (PPIX) evaluated in the subcutaneous tumours. In a pilot study, nine patients with RCC of <4 cm diameter underwent partial nephrectomy; 20 mg ALA/kg body weight was given orally 4 h before surgery. During the operation, the macroscopic fluorescence of the tumours was evaluated and any side-effects recorded. In the mouse model, the RCC fluoresced in all tumours, both macro- and microscopically, reaching a maximum 1.5 h after intravenous and 4 h after oral administration. The tissue concentrations of PPIX in the subcutaneous tumours were also maximal 4 h after oral administration. In the patients undergoing surgery, the RCC also fluoresced clearly and was sufficiently intense to identify the outer margins of the tumours for kidney-preserving tumour resection. There were no side-effects of the ALA with the dosages and methods of administration used. The photodynamic detection of RCC with ALA facilitates the identification of tumour margins in man and in the mouse model, producing no undesirable side-effects. It may be helpful in determining the boundaries of the resected tissue when carrying out conservative kidney-preserving surgery.