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) in breast cancer patients. Currently, radiolabeled colloidal gold and methylene blue (MB) are widely used in the staging of breast cancer. An important goal of the primary project relates to the development of photoacoustic tomography (PAT) method for imaging SLN using MB as contrast agent. The increasing use of single photon emission computed tomography/x-ray computed tomography (SPECT/CT) for lymph node mapping calls for comparative study of both radionuclear and PAT methods. This task-specific project will develop multimodal imaging agents for both PAT and SPECT. Considering that the NTR focuses on translational research, the first product of the study will be based on radiolabeled MB for immediate clinical use. The exploratory component of the project will address key limitations of MB by developing analogous multimodal agent with high absorption coefficient and optimal absorption band in the near infrared (NIR) wavelength (-800 nm) for enhanced 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 for other cancer-related applications but will be evaluated under the context of SLN mapping for the first time. (2) Develop and optimize 123l-cyapte for SPECT/CT and PAT. Cypate is a NIR fluorescent probe that has been shown to be analogous to FDA's approved indocyanine green (ICG). Its high absorption coefficient, low fluorescence quantum yield, and 800 nm absorption are well suited for PAT. Unlike ICG, 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 will demonstrate the feasibility of the multimodal imaging methods before translation to humans. Resources from 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.