PROJECT SUMMARY/ABSTRACT The overall goals of the Sidney Kimmel Comprehensive Cancer Center (SKCCC) Cancer Molecular and Functional Imaging (CMFI) Program are to develop and apply multimodality molecular and functional imaging in cancer discovery and the tumor microenvironment; to identify novel imaging-based targets and advance their translational applications in biomarkers, drug development and theranostics; and to develop artificial intelligence approaches in analyzing images and spectra for diagnosis and prognosis, and for precision medicine. To achieve these overall goals, the CMFI Program has the following four aims that focus on Cancer Discovery and the Tumor Microenvironment, Imaging Agent Development for Detection and Theranostics, Biomarkers and Evaluation of Therapies, and Artificial Intelligence. Aim 1: To use multi- modality molecular and functional imaging to understand cancer and the tumor microenvironment, including the immune microenvironment; Aim 2: To integrate chemistry and molecular biology with imaging to develop novel imaging probes with an emphasis on clinical translation and theranostics; Aim 3: To develop noninvasive biomarkers to allow early identification of cancer, predict risk, assist in the selection of treatment, and detect response. Aim 4: To develop artificial intelligence (AI) approaches applied to image reconstruction and imaging data. We developed Aim 4 as a new aim in the CMFI Program. The four Aims are inter-related within the CMFI Program and highly interactive with other Programs, such as Cancer Genetics and Epigenetics, Cancer Immunology, and Cancer Invasion and Metastasis. The CMFI Program consists of 31 Program full members, 18 of whom have cancer-relevant peer- reviewed funding, and an additional nine associate members. The Program has members with appointments in four departments across two schools at Johns Hopkins. The total direct cancer-relevant peer-reviewed funding is $8.2 million, with $6.9 million from the National Cancer Institute. The total number of publications by Program members since last review is 400, of which 130 (32.5%) are Intra-Programmatic, 147 (36.8%) are Inter-Programmatic and 231 (57.8%) have external collaborations. Of these publications, 10.5% are in journals with impact factors >10 and 2.3% in journals with impact factors >25.