One of the most challenging areas of sensor development for nuclear medicine is the design of proton therapy monitoring systems. Sensors are operated in a high detection rate regime in beam-on conditions. We realized a prototype of a monitoring system for proton therapy based on the technique of positron emission tomography. We used the Plug and Imaging (P&I) technology in this application. This sensing system includes LYSO/silicon photomultiplier (SiPM) detection elements, fast digital multi voltage threshold (MVT) readout electronics and dedicated image reconstruction algorithms. In this paper, we show that the P&I sensor system has a uniform response and is controllable in the experimental conditions of the proton therapy room. The prototype of PET monitoring device based on the P&I sensor system has an intrinsic experimental spatial resolution of approximately 3 mm (FWHM), obtained operating the prototype both during the beam irradiation and right after it. The count-rate performance of the P&I sensor approaches 5 Mcps and allows the collection of relevant statistics for the nuclide analysis. The measurement of both the half life and the relative abundance of the positron emitters generated in the target volume through irradiation of 1010 protons in approximately 15 s is performed with 0.5% and 5% accuracy, respectively.