Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer: In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry.

ABSTRACT

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85-11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04-196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.