We report on tests of a radionuclide imaging system for in vivo investigations in small animals with low-energy photons as from 125I (27-35 keV). Imaging optics features a high-resolution coded aperture mask and a fine pitch hybrid pixel detector (silicon 300-mum or 700-mum thick, or CdTe 1 mm thick) of the Medipix2 series (55 mum pitch, 256 x 256 pixels). The coded aperture had 480 70-mum holes in 100-mum-thick tungsten. Laboratory tests with a 109Cd 22 keV source and a microfocus X-ray tube (35 kVp, Mo anode) show a system resolution of about 110 mum at magnification m = 2.12 and a sensitivity improvement of 30:1 as compared to a 300-mum pinhole collimator. The field of view also depends on magnification: in the experiments presented, it varied from 6 mm (m = 2.12) to 21 mm (m = 0.66). 125I in vivo mouse thyroid imaging with the 70 mum coded aperture, a 300 mum pinhole and a 100 mum parallel hole collimator was also performed to obtain a qualitative comparison. This low energy, semiconductor-based, compact gamma-ray imaging system can be used as a gamma-ray sub-millimeter resolution imager for energies below about 35 keV and it is the basic imaging unit of a small animal Single Photon Emission Computed Tomography system (MediSPECT) built at University of Napoli Federico II and Istituto Nazionale Fisica Nucleare (INFN), Napoli.