TASK-SPECIFIC PROJECTS (4 PAGES/PROJECT, ADDITIONAL ALLOCATION)8.a Task 1: Molecular imaging contrast agents (Samuel Achilefu)8.a.
1 Specific aims Molecular probes play an indispensable role in the detection and imaging of sentinel lymph node (SLN) inbreast cancer patients. Currently, radiolabeled colloidal gold and methylene blue (MB) are widely used in thestaging of breast cancer. An important goal of the primary project relates to the development of photoacoustictomography (PAT) method for imaging SLN using MB as contrast agent. The increasing use of single photonemission computed tomography/x-ray computed tomography (SPECT/CT) for lymph node mapping calls forcomparative study of both radionuclear and PAT methods. This task-specific project will develop multimodalimaging agents for both PAT and SPECT. Considering that the NTR focuses on translational research, the firstproduct of the study will be based on radiolabeled MB for immediate clinical use. The exploratory componentof the project will address key limitations of MB by developing analogous multimodal agent with highabsorption coefficient and optimal absorption band in the near infrared (NIR) wavelength (-800 nm) forenhanced light penetration in tissue. Accordingly, the Specific Aims of this project are to:(1) Prepare and characterize 123I-MB for SPECT/CT and PAT. This agent has been used in humans forother cancer-related applications but will be evaluated under the context of SLN mapping for the firsttime.(2) Develop and optimize 123l-cyapte for SPECT/CT and PAT. Cypate is a NIR fluorescent probe that hasbeen shown to be analogous to FDA's approved indocyanine green (ICG). Its high absorptioncoefficient, low fluorescence quantum yield, and 800 nm absorption are well suited for PAT. UnlikeICG, cypale is useful for producing activity and target-specific molecular probes for tumor imaging.(3) Image lymph nodes by PAT, DOT, and SPECT/CT in mice. The multimodal imaging approach willdemonstrate the feasibility of the multimodal imaging methods before translation to humans. Resourcesfrom the Support Core (SPECT/CT) and other Task-Specific Projects (see Projects 8c and 8d below)will be used to complete this section of the proposal.
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