PROJECT SUMMARY More than half of all cancer patients in the United States receive Radiation Therapy (RT) as a part of their cancer treatment (>500,000 patients per year). Cancer patients typically receive a highly targeted dose of radiation over the course of days or weeks. Each patient will typically receive 25-40 daily treatments. Treatment outcome is dependent on accurate delivery of radiation. All RT patient treatment plans are based on a planning `simulation' CT scan, acquired days or weeks before the start of treatment. However, due to weight loss or tumor shrinkage in the time between simulation and treatment, anatomical changes may lead to healthy tissues being irradiated. Side effects of irradiating healthy tissue can be severe. Adaptive optimizing has chance . However, the implementation of ART is severely limited by the lack of a real-time device that can accurately measure the delivered radiation distribution within the patient. Currently no system exists which is capable of measuring the radiation dose distribution within the patient. RT (ART) – re- the radiation distribution based on the patient's daily anatomy in order to maintain the plan quality – been proposed as a means to deliver more radiation with reduced normal tissue damage; increasing the of a cure, with fewer side effects This project will address this need by developing the first contrast agent for imaging radiation therapy. Our approach will employ the x-ray acoustic (XA) effect, which is analogous to the “photoacoustic effect”, a physical phenomenon whereby acoustic waves are generated by the absorption of heat energy from a pulsed photon beam. In XA Computed Tomography (XACT), the photon beam is high-energy x-ray radiation generated by a medical linear accelerator (LINAC) used in clinical radiation therapy. Novel XA contrast agents are needed to improve XACT imaging and are essential to our concept of XACT dosimetry. Toward this end, we recently invented vaporizable endoskeletal drops (VEDs) comprising a liquid fluorocarbon droplet with a solid hydrocarbon “skeleton”. We discovered that the liquid fluorocarbon droplet vaporizes upon heating and melting of the hydrocarbon solid. The drop-to-bubble expansion emits an acoustic wave that can be imaged with XACT, and the resulting microbubble is echogenic for ultrasound imaging. This project will develop the VED technology into a novel radiation therapy contrast agent for XACT by 1) Formulation of VEDs comprising high-z metal ions within the hydrocarbon skeletal phase to absorb x-rays and stimulate vaporization; and 2) Measurement of the XA effect of high-z VEDs. Completing these aims will enable future commercialization, in vivo preclinical testing, and clinical translation.