Liver cancer ranks the third most common cause of cancer related mortality worldwide. Radiomicrosphere therapy (RMT), a form of radiation therapy, involves administration of Yttrium-90 (90Y) microspheres to the liver via the hepatic artery. 90Y microspheres bremsstrahlung SPECT/CT or PET/CT imaging could potentially identify an extrahepatic uptake. An early detection of such an uptake, thus, could initiate preventative measures early on. However, the quantitative accuracy of bremsstrahlung SPECT/CT images is limited by the wide and continuous energy spectrum of 90Y bremsstrahlung photons. 90Y PET/CT imaging is also possible but limited by the extremely small internal pair production decay. These limitation lead to inaccurate quantitation of microsphere biodistribution especially in small tumors. SPECT/CT and PET/CT acquisition of a Jasczak phantom with eight spherical inserts filled with 90Y3Cl solution were performed to measure the quantitative accuracy of the two imaging modalities. 90Y microsphere SPECT/CT data of 17 patients who underwent RMT for primary or metastatic liver cancer were acquired. Technetium-99m macroaggregated albumin (99mTc-MAA) SPECT/CT scans were also collected, but available for only twelve of the patients. SPECT/CT images from phantoms were used to determine the optimal iteration number for the iterative spatial resolution recovery algorithm. Methods for image based calculation of calibration factors for activity estimation from the patient and phantom 90Y bremsstrahlung SPECT/CT images were developed. Tumor areas were segmented using an active contour method. The 99mTc-MAA and 90Y microsphere SPECT/CT images were co-registered a priori for correlation analysis. Comparison of uptake on 99mTc-MAA and 90Y microsphere SPECT/CT images was assessed using tumor to healthy liver ratios. Furthermore, a three dimensional absorbed dose estimation algorithm was developed using the voxel S-value method. Absorbed doses within the tumor and healthy part of the liver were investigated for correlation with administered activity. Improvement in contrast to noise ratio and contrast recovery coefficients (QH) on patient and phantom 90Y bremsstrahlung SPECT/CT images as well as PET/CT images were achieved. Total activity estimations in liver and phantom gave mean percent errors of -4 ± 12% and -23 ± 41% for patient and phantom SPECT/CT studies. The pre and post-treatment images showed significant correlation (r = 0.9, p < 0.05) with mean TLR of 9.2 ± 9.4 and 5.0 ± 2.2 on 99mTc-MAA and 90Y microspheres SPECT/CT respectively. The correlation between the administered activity and tumor absorbed dose was weak (r = 0.5, p > 0.05), however, healthy liver absorbed dose increased with administered activity (r = 0.8, p < 0.05).