Background: Cancer is first-leading cause of adult deaths. Radiation therapy based on x-rays cure approximately 50% of all cancer patients and is a fundamental pillar in cancer treatment. But, collateral damage of healthy surrounding tissues is unavoidable. Proton beams differ from x-rays by the fact that their penetration depth is sharply determined and release their energy at the Bragg peak. The problem: In proton beam therapy the dosimetry is determined by simulations of the proton deposition in the tissue. However, organ movement and errors in the assumed material properties lead to inaccuracy of the deposition. The Solution: We propose a non-invasive, in-situ, real-time localization system for proton therapy monitoring using ultrasound contrast agents and highly sensitive optical-acoustical receivers. Our concept consists of two innovative steps. The first step is the interaction of the proton beam with a medical ultrasound contrast agent consisting of coated microbubbles. The energy deposition from individual protons in the Bragg peak creates a broadband excitation in the vicinity of the bubble forcing them to vibrate at their resonance frequency (1-10 MHz). This creates a low amplitude pressure wave that can be used for localization and dose measurement of the proton beam. The second step entails the development of an array of ultra-sensitive acousto-optical ultrasound sensors for detecting the acoustic pressure waves generated by the microbubbles, which is one order of magnitude below the detection limit of current state-of-the-art ultrasonic sensors. Acousto-optical sensors consist of a silicon chip with an extremely thin membrane that will already be deflected by very small acoustic pressure amplitudes. This deflection will be detected by a micro-optical circuit that is integrated on the membrane. Using the microbubbles and these highly sensitive receivers allows for a real-time monitoring of the proton deposition with a spatial resolution better than 1 mm.