BackgroundThe overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer. Here, we report the synthesis and characterization of polymeric phospholipid-based nanomicelles encapsulating near-infrared (NIR) phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin [Pt(TPNP)] and surface functionalized with gadolinium [Pt(TPNP)-Gd] for combined magnetic resonance imaging (MRI) and NIR optical imaging applications.MethodsDynamic light scattering, electron microscopy, optical spectroscopy and MR relaxometric measurements were performed to characterize the optical and magnetic properties of nanoparticles in vitro. Subsequently, in vivo imaging experiments were carried out using nude mice bearing primary patient tumor-derived human head and neck squamous cell carcinoma xenografts.ResultsThe nanomicelles were ~100 nm in size and stable in aqueous suspension. T1-weighted MRI and relaxation rate (R1 = 1/T1) measurements carried out at 4.7 T revealed enhancement in the tumor immediately post injection with nanomicelles, particularly in the tumor periphery which persisted up to 24 hours post administration. Maximum intensity projections (MIPs) generated from 3D T1-weighted images also demonstrated visible enhancement in contrast within the tumor, liver and blood vessels. NIR optical imaging performed (in vivo and ex vivo) following completion of MRI at the 24 h time point confirmed tumor localization of the nanoparticles. The large spectral separation between the Pt(TPNP) absorption (~700 nm) and phosphorescence emission (~900 nm) provided a dramatic decrease in the level of background, resulting in high contrast optical (NIR phosphorescence) imaging.ConclusionsIn conclusion, Pt(TPNP)-Gd nanomicelles exhibit a high degree of tumor-avidity and favorable imaging properties that allow for combined MR and optical imaging of head and neck tumors. Further investigation into the potential of Pt(TPNP)-Gd nanomicelles for combined imaging and therapy of cancer is currently underway.
In this report, we determined the feasibility to combine fluorescent protein imaging (FPI) and magnetic resonance imaging (MRI) to demonstrate the efficacy of selenium on tumor progression and angiogenesis of colon cancer in an orthotopic model. GEO human colon carcinoma cells expressing green fluorescent protein (GFP), were implanted orthotopically into the colon of athymic nude mice. Beginning 5 days post implantation, whole body FPI was performed to monitor tumor growth in vivo. Upon visualization of tumor growth by FPI, animals were randomly assigned to either a control group or a treatment group. Treatment consisted of daily oral administration of the organoselenium compound, methyselenocysteine (MSC; 0.2 mg/day × 5 weeks). Longitudinal monitoring of tumor growth was performed using FPI and MRI. In addition, dynamic contrast-enhanced MRI was performed to examine the change in tumor blood volume following treatment. Changes in tumor vascularity visualized by imaging were correlated with immunohistochemical determination of microvessel density. Both FPI and MRI allowed non-invasive visualization of the longitudinal growth of orthotopic colon tumors. While T1- and T2-weighted MRI provided adequate contrast and volumetric assessment of GEO tumor growth, GFP imaging allowed for high-throughput visualization of tumor progression. Selenium treatment resulted in a significant reduction in blood volume and microvessel density of GEO tumors. A significant inhibition of tumor growth was also observed in selenium-treated animals compared to untreated control animals. Together, these results highlight the usefulness of multimodal imaging approaches to demonstrate antitumor and anti-angiogenesis efficacy and the potential of selenium treatment of colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4284. doi:10.1158/1538-7445.AM2011-4284
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