We have designed for cerebral imaging a next-generation multi-pinhole system, AdaptiSPECT-C. This prototype incorporates 24 detector modules and can provide a total of up to 120 pinholes in multiple combinations around the brain. The system can adapt each aperture to one of three sizes and whether it is open or closed via a shutter mechanism. AdaptiSPECT-C provides high-performance patient-personalized imaging in various brain imaging procedures. In this work we initially determined the pinhole size and combination of AdaptiSPECT-C for optimal single- and dual-isotope 99mTc-HMPAO perfusion/123I-Ioflupane DaT imaging. We found through quantification and visual inspection that the medium aperture size in a central plus obliques pinhole combination for the adaptable AdaptiSPECT-C system is the most suited for high-performance single- and dual-isotope perfusion and DaT imaging. We observed that the use of the largest pinhole size degrades visually and in terms of NRMSE and %SBR, the reconstructions despite higher sensitivity due to lower spatial resolution compared to that of the medium aperture diameter. For simultaneous imaging, we investigated an extreme case for which the two symmetric photopeak windows slightly overlap with each other and the crosstalk contamination (∼20% and ∼10% for the 99mTc and 123I photopeaks) was not corrected. Our initial results suggest that the reconstructions obtained from the dual-isotope study remain close quantitively and visually to that of the single-isotope simulations. We observed that the obliques or obliques plus central combination is more affected by crosstalk contamination than the central-only configuration.