Nanodelivery of MRI Contrast Agent Enhances Sensitivity of Detection of Lung Cancer Metastases

Abstract

Early detection of lung cancer can be problematic. Although current imaging methods can identify lung cancers, they are limited in the size of detectable nodules. There is also lack of evidence that these methods can correctly classify nodules <7 mm as malignant because lung cancer can be mimicked in appearance by benign lesions that lower specificity. Therefore, there is a need for enhanced sensitivity/specificity of detection for small lung cancers. We have developed a nanosized ( approximately 100 nm) immunoliposome complex for delivery of molecular medicines to tumors. In this complex, an anti-transferrin receptor single-chain antibody fragment (TfRscFv) decorates the surface of a cationic liposome encapsulating the payload. We have previously shown that this systemically administered complex (scL) selectively targets, and efficiently delivers its payload into, tumor cells. We have also encapsulated the magnetic resonance imaging (MRI) contrast agent gadopentetate dimeglumine ("gad-d") within this complex, resulting in increased resolution and image intensity in a mouse model of primary cancer. Here we examine the ability of the scL-gad-d complex to increase the sensitivity of detection of lung metastases. These MRI studies show that the scL-gad-d nanocomplex is able to improve detection, and increase enhancement of, small lung cancers (400 microm and as small as 100 microm) compared to that of uncomplexed gad-d. Because of its tumor targeting specificity, deliver of an MRI contrast agent via this nanocomplex has potential for use as an agent that can identify small lung cancers, thus improving early detection and possibly increasing survival.