Nanodelivery of MRI Contrast Agent Enhances Sensitivity of Detection of Lung Cancer Metastases
Received 13 November 2007; accepted 15 December 2008.
Rationale and Objectives
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.
Materials and Methods
We have developed a nanosized (∼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.
Results
These MRI studies show that the scL-gad-d nanocomplex is able to improve detection, and increase enhancement of, small lung cancers (400 μm and as small as 100 μm) compared to that of uncomplexed gad-d.
Conclusions
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.
Department of Oncology, Lombardi Comprehensive Cancer Center, TRB/E420, Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC, 20057-1469 (M.F., E.H.C., Q.Z., K.F.P.)
Address correspondence to: E.H.C.
Supported in part by STTR Phase I grant 1R41 CA 121453-01 (E.H.C., M.F., K.F.P.), and a research grant from SynerGene Therapeutics (K.F.P.). These studies were conducted in part using the Histopathology and Tissue, and Animal Core Facilities supported by NCI Cancer Center Support grant and USPHS grant 2P30-CA-51008 and 1 S10 RR 15768-01. This investigation was conducted in part in a facility constructed with support from Research Facilities Improvement grant C06RR14567 from the National Center for Research Resources, National Institutes of Health, Bethesda, MD.
ABSTRACT