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Purpose Beta-particle radioguided tumor resection may potentially overcome the limitations of conventional gamma-ray guided surgery by eliminating, or at least minimizing, the confounding effect of counts contributed by activity in adjacent normal tissues. The current study evaluates the clinical feasibility of this approach for a variety of radionuclides. Nowadays, the only β - radioisotope suited to radioguided surgery is 90Y. Here, we study the β - probe prototype capability to different radionuclides chosen among those used in nuclear medicine. Methods The counting efficiency of our probe prototype was evaluated for sources of electrons and photons of different energies. Such measurements were used to benchmark the Monte Carlo (MC) simulation of the probe behavior, especially the parameters related to the simulation of the optical photon propagation in the scintillation crystal. Then, the MC simulation was used to derive the signal and the background we would measure from a small tumor embedded in the patient body if one of the selected radionuclides is used. Results Based on the criterion of detectability of a 0.1 ml tumor for a counting interval of 1 s and an administered activity of 3 MBq/kg, the current probe yields a detectable signal over a wide range of Standard Uptake Values (SUVs) and tumor-to-non-tumor activity-concentration ratios (TNRs) for 31Si, 32P, 97Zr, and 188Re. Although efficient counting of 83Br, 133I, and 153Sm proved somewhat more problematic, the foregoing criterion can be satisfied for these isotopes as well for sufficiently high SUVs and TNRs.