IntroductionYttrium‐90 (90Y) microsphere post‐treatment imaging reflects the true distribution characteristics of microspheres in the tumor and liver compartments. However, due to its decay spectra profile lacking a pronounced photopeak, the bremsstrahlung imaging for 90Y has inherent limitations. The absorbed dose calculations for 90Y microspheres radiomicrosphere therapy (RMT) sustain a limitation due to the poor quality of 90Y imaging. The aim of this study was to develop quantitative methods to improve the post‐treatment 90Y bremsstrahlung single photon emission tomography (SPECT)/computed tomography (CT) image analysis for dosimetric purposes and to perform a quantitative comparison with the 99mTc‐MAA SPECT/CT images, which is used for theranostics purposes for liver and tumor dosimetry.MethodsPre and post‐treatment SPECT/CT data of patients who underwent RMT for primary or metastatic liver cancer were acquired. A Jasczak phantom with eight spherical inserts of various sizes was used to obtain optimal iteration number for the contrast recovery algorithm for improving 90Y bremsstrahlung SPECT/CT images. Comparison of uptake on 99mTc‐MAA and 90Y microsphere SPECT/CT images was assessed using tumor to healthy liver ratios (TLRs). The voxel dosimetry technique was used to estimate absorbed doses. Absorbed doses within the tumor and healthy part of the liver were also investigated for correlation with administered activity.ResultsImprovement in CNR and contrast recovery coefficients on patient and phantom 90Y bremsstrahlung SPECT/CT images respectively were achieved. The 99mTc‐MAA and 90Y microspheres SPECT/CT images showed significant uptake correlation (r = 0.9, P = 0.05) with mean TLR of 9.4 ± 9.2 and 5.0 ± 2.2, 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 = 0.0).ConclusionsThis study demonstrated correlation in mean TLR between 99mTc‐MAA and 90Y microsphere SPECT/CT.