Enhancing MRI of liver metastases with a zwitterionized biodegradable dendritic contrast agent

Abstract

Metastasis is the main reason for cancer-associated mortality, and accurate diagnostic imaging of metastases is critical for the clinical administration and tailoring personalized treatments for metastatic tumors. However, magnetic resonance imaging of metastases in the liver is impeded by its low sensitivity because the currently used contrast agents accumulate in hepatocytes and Kupffer cells instead of cancer cells. Herein, a 4^th generation zwitterionized biodegradable dendritic contrast agent (DCA) with a size of ca. 9 nm and a longitudinal relaxivity of 15.7 mM⁻¹ s⁻¹ in terms of Gd was synthesized and used to enhance the MRI of liver metastasis. The DCA could remarkably enhance the MRI of metastasized tumors in the liver, because it could simultaneously reduce the background signal in the liver by avoiding uptake by hepatocytes and Kupffer cells through the zwitterionization and increase the signal in tumors through the enhanced permeability and retention effect. Moreover, in contrast to non-biodegradable DCA, this DCA showed minimal long-term Gd³⁺ retention in all organs and tissues because it could be degraded into small fragments. The significant capability of enhancing the MRI of metastases in the liver plus its excellent biodegradability made this DCA a promising CA for metastatic tumor imaging.