Accurate and timely staging of prostate cancer (PCa) is essential for matching patients with the appropriate treatment. Noninvasive staging techniques using anatomical imaging alone are inadequate and extensive research efforts have focused on molecular imaging agents that exploit the in-vivo mechanisms of PCa. There is considerable potential for SPECT for molecular imaging of the prostate. One SPECT agent now in use is ProstaScint, an In-111-radiolabeled monoclonal antibody for detecting soft-tissue PCa metastases in the lymph nodes of the pelvis and abdomen. ProstaScint has FDA approval for the evaluation of newly diagnosed cases as well as treated patients who are at risk of recurrence, but interpretation of ProstaScint scans is challenging enough that few institutions offer the imaging test. Inherent weaknesses with the clinical protocol for ProstaScint imaging contribute to this problem. The standard SPECT systems with rotating camera heads and medium-energy parallel-hole (MEPAR) collimators to control septal penetration of the In-111 gamma rays deliver relatively poor photon sensitivity and spatial resolution. We hypothesize that practical alternatives to MEPAR SPECT are available to significantly improve ProstaScint imaging. Novel multipinhole (MPH) systems dedicated to cardiac imaging have recently shown impressive results surpassing the spatial resolu- tion and detection efficiency of parallel-hole collimation. The goal of this proposal is to investigate the utility of MPH SPECT for imaging PCa. Working in simulation, we shall apply the paradigm of task-based technology assessment to evaluate diagnostic performances. Among our objectives is the design and optimization of a novel MPH system dedicated to prostate imaging. The specific aims of this proposal are: 1) implemention of procedures for simulating sets of clinically realistic PCa images;2) optimization of MPH SPECT designs for imaging PCa;and 3) comparison of MPH and MEPAR SPECT for diagnostic prostate imaging. A unique element of our approach is the utilization of numerical observers intended to mimic human observers for clinically realistic tasks of interest, offering the potential for accurate predictions of human performance over a wide array of clinically relevant tasks. Our long-term objective is to improve SPECT imaging of PCa. It is expected that such improvements would help not only with ProstaScint but also with future prostate-specific SPECT agents that may be introduced into the clinic. Overall, completion of the project aims could translate to improved staging and more effective management of PCa, reducing patient risks and enhancing response to therapy.