Collimator-detector response function (CDRF) of a SPECT scanner refers to the image generated from a point source of activity. This research aims to characterize the CDRF of a breast-dedicated SPECT imager equipped with a lofthole collimator using GATE Monte Carlo simulation. To do so, a cylindrical multi-lofthole collimation system with lofthole apertures dedicated to breast imaging was modeled using the GATE Monte Carlo simulator. The dependency of the CDRF on the source-to-collimator distance of a single-lofthole as well as 8-lofthole collimations was assessed and then compared. In addition, the 3D-sensitivity map of the 8-lofthole collimation was derived. Finally, fair comparisons were conducted between the response of the 8-lofthole collimator and that of an 8-pinhole and also existing analytical derivations. In all cases, a data acquisition period of 5.0 min with an in-air 99mTc point source was considered. For the single-lofthole collimator, 4.5 times increasing the magnification factor leads to a 16- and twofold improvement in the sensitivity and spatial resolution, respectively. In the single-lofthole collimator, the resolution and sensitivity are degraded as the source-to-aperture distance increases. For the cylindrical 8-lofthole collimator, the findings confirm that CDRF strongly depends on source-to-aperture distance and angle of photon incidence. For a 30 mm in-plane offset point, a 25% increase in sensitivity is observed compared to that of the center of the FOV. Increasing the angle from 0 to 34 results in a 50% reduction in sensitivity. Furthermore, the findings illustrate that spatial resolution follows a quadratic function as where d is an offset along the x-, y-, and z-axis, and R0 is the spatial resolution at the center of the FOV. In conclusion, both spatial resolution and sensitivity of the lofthole collimation are considerably angle- and offset-dependent within the FOV of single- and multi-lofthole collimated SPECT imagers.