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

Abstract

Objective: 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.

Patients, materials and methods: 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.

Results: 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.

Conclusion: 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.