In In-111-pentetreotide SPECT, it can be difficult to detect small tumors because of high noise levels and low spatial resolution. The aim of this study was to perform optimization of tumor detection in the liver, with regards to the acquisition and reconstruction protocol for In-111-pentetreotide SPECT with model-based compensation included in the OSEM reconstruction. We were also interested in the effect of performing the examination in half of the time or with half the administered activity. Image reconstruction without model-based compensation was also included for comparison. The study concentrates on the acquired number of projections and the subset size in the OSEM reconstruction, and evaluates contrast as a function of noise for a range of OSEM iterations. The raw-data projections are produced using Monte Carlo simulations of a patient-like anthropomorphic phantom with realistic In-111 pentetreotide uptake, including spherical tumors in the liver. Two collimators are evaluated, the extended low-energy general-purpose (ELEGP) and the medium-energy general-purpose (MEGP) collimator. ELEGP proved to be a better collimator when using model-based compensation. The results also indicate that a relatively low number of subsets is advantageous, and that 60 projection angles or even lower is a better choice than 120. For both collimators the time-reduced scan including model-based compensation was better compared to the full-time reconstructions without model-based compensation.