Extravasation of Pt-based chemotherapeutics – bioimaging of their distribution in resectates using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS)

Abstract

Platinum-based drugs (cisplatin, carboplatin and oxaliplatin) are widely used in cancer treatment. They are administered intravenously, thus accidental extravasations of infusions can occur. This may cause severe complications for the patient as the toxic platinum compounds likely persist in subcutaneous tissue. At high concentrations, platinum toxicity in combination with local thrombosis may result in tissue necrosis, eventually requiring surgical intervention. To describe tissue distribution at the anatomic level, we quantified drug extravasation in cryosections of various tissues (muscle, nerve tissue, connective tissue, fat tissue) by means of quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and compared the resulting data with bulk analysis of microwave-assisted digestion of tissue samples followed by ICP-MS analysis. Samples of three patients receiving systemic chemotherapy either via peripheral venous access or central access via port-a-cath® were analyzed. Pt was enriched up to 50-times in connective tissue when compared with muscle tissue or drain samples collected over five days. The large areas of subcutaneous fat tissue showed areactive necrosis and average Pt concentrations (determined upon sample digestion) ranged from 0.2 μg g⁻¹ (therapy with 25 mg m⁻² cisplatin, four weeks after peripheral extravasation) to 10 μg g⁻¹ (therapy with 50 mg m⁻² oxaliplatin: four weeks after port-a-cath® extravasation). A peripheral nerve subjected to bioimaging by LA-ICP-MS showed a 5-times lower Pt concentration (0.2 μg g⁻¹) than the surrounding connective tissue (1.0 μg g⁻¹). This is in accordance with the patient showing no signs of neurotoxicity during recovery from extravasation side-effects. Thus, bioimaging of cutaneous nerve tissue may contribute to understand the risk of peripheral neurotoxic events.