Current Projects

Fluorescence lifetime imaging

We have been investigating whether fluorescent lifetime imaging may be used to obtain functional information regarding local concentrations of specific substances such as O2, or information about environmental conditions such as temperature and pH. Quantification requires a fluorophore with a known dependence on the environmental factor. For deeply embedded sites in a turbid medium such as tissue, measuring the photon arrival delay caused by a specific fluorophore lifetime is made difficult by the photon arrival delays caused by multiple scattering of the photon on its transit through the tissue. However, RWT is well suited to solving this type of problem. The delay of photons that results from the excitation and later emission by a fluorophore can be modeled in RWT in the same way as transit delays due to multiple scattering. Hence, we have derived a RWT closed-form solution for time-resolved fluorescent lifetime imaging. This is now being tested with fluorophore-impregnated agarose phantoms. We have entered into two collaborative projects that will make use of the results of these studies. In collaboration with the Radiation Biology Program of the NCI, we have begun a mouse imaging study that will utilize malignant cells transfected with the gene(s) for synthesis of fluorescent proteins. In a second project we are investigating the use of IR-dependent fluorescent detection methods as alternatives to radionucleotide detection to determine the locations of sentinel lymph nodes for surgical treatment of cancer.

Noninvasive in-vivo optical imaging to quantify integrin in tumor

(in collaboration with the Radiation Oncology Branch, NCI, NIH)

Angiogenesis is the process by which new blood vessels develop from pre-existing vessels. The new blood vessels play a key role in the physiological development of cancerous tumors. Integrins are receptor proteins that play a critical role in regulating several tumor cells growth. Integrin (avß3) can provide specific cell survival signals that facilitate vascular cell proliferation during angiogenesis. Establishment of a noninvasive technique to visualize and quantify integrin level in vivo will allow us to understand the intrinsic relationship between integrin expression and specific tumor cell growth at an early stage andmonitor metastasis. Targeting these integrins can be possible with arginine-glycine-aspartic acid (RGD) containing peptides. Optical imaging (fluorescence), a noninvasive method for quantitative evaluation of integrin expression in tissue, would greatly aid the study of tumor biology even at early stage. In this protocol non-invasive optical imaging will be tested as a mean of providing a scientifically reproducible means of assessing different types of tumor cells growth by measuring integrin level in tumor. Currently several integrin inhibitors are under investigation as therapeutics for cancer. Therefore, this integrin-based angiogenesis study holds great promise to understand tumor physiology as well as powerful tool for the treatment of cancer. Hypothesis: Expression of integrin subunits may precede angiogenesis associated with establishment of metastasis site or growth of tumor. Identification and quantification of integrin expression could lead to earlier diagnosis of cancer sites and earlier intervention.

Targeting external receptors (HER1-4, IGFR) in mice bearing tumor xenografts

(in collaboration with the Radiation Oncology Branch, NCI, NIH)

Non-invasive monitoring of receptor expression in tumor is extremely important for patient undergoing treatment with therapy. A novel small animal imaging system has been developed with an excitation source and multiple detection fibers separated from the source at different distances. This configuration may allow us to reconstruct tomographic image of intensity and lifetime at different depth. The goal of our study is to develop a non-invasive optical method for monitoring of HER2 in-vivo and HER2-specific delivery of therapeutic agents to individualize treatment of HER2-positive cancers (breast cancer). Affibody molecules have been used in this study which represents a new class of affinity proteins specific for HER2. Breast cancer cells were implanted in the flank area of the mice. These cells express high levels of HER2 (HER2/neu, c-ErbB2) protein. Using a tail injected fluorescent probe: protein conjugated Alexa Fluor 750 to tumor infiltrating molecules and mapping a 2D image of the intensity and lifetime in vivo. The results showed that specific binding to HER2 receptors which was not affected by pretreatment of the target tumor cells with Herceptin (therapeutic drug). This study will allow non-invasively identifying of patients suitable for targeted therapy designed against HER2-positive tumors and also provide means to monitor the immediate response (receptor down-regulation) to therapy.

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