This study aims to investigate the possibility of implementing serial autoradiography using a silicon strip detector as an imaging modality in pre-clinical radionuclide therapy research, in order to study the effect of non-uniform uptake on absorbed dose distribution and biological response. Tumor tissues expressing CD20 (B-cell lymphoma) or carcinoembryonic antigen (CEA; colorectal cancer) were excised from animals injected with mI-labelled anti-CD20 or anti-CEA antibodies and antibody fragments. The tumors were cryosectioned at 100 mum and imaged using a real-time silicon- strip imager with a pixel-size of 50 mum. Software was developed to correct for image artifacts and to realign the image sections into a volume by a two-step process with least square error and mutual information registration measures. The realigned volumes were convolved with beta dose point kernels to provide the dose rate distribution for 131I and 90Y at the time of sacrifice. Using these volumes, comparisons can be made between uptake and penetration of different antibodies and the dose rate uniformity of different radionuclides. Simulations performed using measured 131I and 125I energy spectra showed that energy separation with less than 5% error could be performed with 100 counts per pixel. Imaging and subsequent separation of a sample containing both 131I and 125I proved the possibility of simultaneous imaging of two targeting agents in the same tissue. Thinner tissue sections were also set aside and successfully used for H&E staining and immunohistochemistry to enable future comparison of uptake and dose rate in different cell-type populations in the tissue. This method successfully provides high-resolution activity and dose rate volumes and has potential for multi-labeling imaging and co-registration with histology. As a complimentary imaging modality it can aid in investigating the effect of non-uniform uptake. Opti- mization is still needed in both the sectioning protocol and realignment software.