The biggest single problem that prevents a dramatic reduction in the mortality due to cancer is the limitation on current medical imaging techniques, computed tomography (CT) and magnetic resonance imaging (MRI), that provide detailed anatomical snapshots of the body but fail to provide accurate, basic information necessary to manage the patient's disease optimally. The limitations are manifested in several ways: (1) Small primary tumors go undetected. (2) Metastatic disease is grossly underdiagnosed. (3) Treatment response to therapy is poorly measured. A related problem in cancer therapy is the lack of selectivity of chemotherapeutic agents that are toxic to proliferating cells. The resulting side effects limit dosing and prevent use altogether. A solution to this problem is to selectively carry contrast agents and drugs into cancer cells so as to enhance uptake and selectivity. As one approach, we have developed a highly adaptable amphiphilic alternating copolymer system that self-assembles into micelles for in vivo imaging agent and therapeutic delivery applications in cancer. The key feature of our adaptable synthetic scheme is the enzymatic polymerization of multifunctional linker molecules with poly(ethylene glycol). This chemo-enzymatic synthesis is much faster and more convenient than an entirely chemical synthesis. We have developed various subsequent syntheses to attach peptides (for targeting), perfluorocarbons (19F MR imaging), fluorescent dyes (NIRF imaging), and radioiodine (nuclear imaging and radioimmunotherapy) to this functionalized backbone. Attachment of a hydrophobic sidechain, which is unnecessary if perfluorocarbons are attached, completes the synthetic scheme producing multimodal self-assembling nanoparticles. The chemotherapeutic, doxorubicin, has also been encapsulated. These unique alternating copolymer micelle nanoparticles were designed as delivery vehicles targeted to human cancer cells expressing the underglycosylated mucin-1 antigen, which is found on almost all epithelial cell adenocarcinomas. These nanoparticles have a number of advantages including the following: (1) The probes are small (10-100 nm in diameter), which increases uptake into tumors by the enhanced permeability and retention (EPR) effect of tumor vasculature. (2) Uptake can be selectively enhanced by the targeting peptide. (3) The probes have potentially high carrying capacity for bound and encapsulated imaging and therapeutic agents. (4) The components are highly interchangeable in both their size and character, providing opportunity to readily adjust micelle properties like size, stability, and encapsulation preference. In vitro and in vivo studies addressing specificity, toxicity, and imaging and treatment efficacy are underway.