Molecular ultrasound imaging is used to image the expression of specific proteins on the surface of blood vessels using the conjugated microbubbles (MBs) that can bind to the targeted proteins, which makes MBs ideal for imaging the protein expressed on blood vessels. However, how to optimally apply MBs in an ultrasound imaging system to detect and quantify the targeted protein expression needs further investigation. To address this issue, objective of this study is to investigate feasibility of developing and applying a new quantitative imaging marker to quantify the expression of protein markers on the surface of cancer cells. To obtain a numeric value proportional to the amount of MBs that bind to the target protein, a standard method for quantification of MBs is applying a destructive pulse, which bursts most of the bubbles in the region of interest. The difference between the signal intensity before and after destruction is used to measure the differential targeted enhancement (dTE). In addition, a dynamic kinetic model is applied to fit the timeintensity curves and a structural similarity model with three metrics is used to detect the differences between images. Study results show that the elevated dTE signals in images acquired from the targeted (MBTar) and isotype (MBIso) are significantly different (p<0.05). Quantitative image features are also successfully computed from the kinetic model and structural similarity model, which provide potential to identify new quantitative image markers that can more accurately differentiate the targeted microbubble status.
Cerenkov luminescence imaging (CLI) is an emerging cost effective modality that uses conventional small animal
optical imaging systems and clinically available radionuclide probes for light emission. CLI has shown good correlation
with PET for organs of high uptake such as kidney, spleen, thymus and subcutaneous tumors in mouse models. However,
CLI has limitations for deep tissue quantitative imaging since the blue-weighted spectral characteristics of Cerenkov
radiation attenuates highly by mammalian tissue. Large organs such as the liver have also shown higher signal due to the
contribution of emission of light from a greater thickness of tissue. In this study, we developed a simple model that
estimates the effective tissue attenuation coefficient in order to correct the CLI signal intensity with a priori estimated
depth and thickness of specific organs. We used several thin slices of ham to build a phantom with realistic attenuation.
We placed radionuclide sources inside the phantom at different tissue depths and imaged it using an IVIS Spectrum
(Perkin-Elmer, Waltham, MA, USA) and Inveon microPET (Preclinical Solutions Siemens, Knoxville, TN). We also
performed CLI and PET of mouse models and applied the proposed attenuation model to correct CLI measurements.
Using calibration factors obtained from phantom study that converts the corrected CLI measurements to %ID/g, we
obtained an average difference of less that 10% for spleen and less than 35% for liver compared to conventional PET
measurements. Hence, the proposed model has a capability of correcting the CLI signal to provide comparable
measurements with PET data.
MicroRNAs (miRNAs) are one of the most prevalent small (~22 nucleotide) regulatory RNA classes in
animals. These miRNAs constitute nearly one percent of genes in the human genome, making miRNA genes
one of the more abundant types of regulatory molecules. MiRNAs have been shown to play important roles
in cell development, apoptosis, and other fundamental biological processes. MiRNAs exert their influence
through complementary base-pairing with specific target mRNAs, leading to degradation or translational
repression of the targeted mRNA. We have identified and tested a novel microRNA (miR-491) and
demonstrated increased apoptosis in hepatocellular carcinoma cells (HepG2) and in human breast cancer
cells (HBT3477) in vitro. We prepared a novel cancer targeting assembly of gold nanoparticles (GNP) with
Quantum dots, miR-491, and MAb-ChL6 coupled through streptavidin/biotin for effective transfection, and
to induce apoptosis in specific cancer cells for imaging and targeted therapy. The targeting and apoptosis
inducing ability was tested by confocal and electron microscopy. The MAb-GNP-miR491-Qdot construct
effectively transfected into the HBT3477 cells and induced apoptosis the confirmation of these results would
suggest a new class of molecules for the imaging and therapy of breast cancer.
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