BackgroundMonte Carlo (MC) simulations are used in nuclear medicine imaging as they provide unparalleled insight into processes that are not directly experimentally measurable, such as scatter and attenuation in an acquisition. Whilst MC is often used to provide a ‘ground-truth’, this is only the case if the simulation is fully validated against experimental data. This work presents a quantitative validation for a MC simulation of a single-photon emission computed tomography (SPECT) system.MethodsAn MC simulation model of the Mediso AnyScan SCP SPECT system installed at the UK National Physical Laboratory was developed in the GATE (Geant4 Application for Tomographic Emission) toolkit. Components of the detector head and two collimator configurations were modelled according to technical specifications and physical measurements. Experimental detection efficiency measurements were collected for a range of energies, permitting an energy-dependent intrinsic camera efficiency correction function to be determined and applied to the simulation on an event-by-event basis. Experimental data were collected in a range of geometries with ^{99text {m}}Tc for comparison to simulation. The procedure was then repeated with ^{177}Lu to determine how the validation extended to another isotope and set of collimators.ResultsThe simulation’s spatial resolution, sensitivity, energy spectra and the projection images were compared with experimental measurements. The simulation and experimental uncertainties were determined and propagated to all calculations, permitting the quantitative agreement between simulated and experimental SPECT acquisitions to be determined. Statistical agreement was seen in sinograms and projection images of both ^{99text {m}}Tc and ^{177}Lu data. Average simulated and experimental sensitivity ratios of (0.991 pm 0.011) were seen for emission and scatter windows of ^{99text {m}}Tc, and (0.897 pm 0.014) and (0.839 pm 0.014) for the 113 and 208 keV emissions of ^{177}Lu, respectively.ConclusionsMC simulations will always be an approximation of a physical system and the level of agreement should be assessed. A validation method is presented to quantify the level of agreement between a simulation model and a physical SPECT system.