Aim/Introduction: Respiratory motion compromises 99mTc-MAA SPECT image quality and quantitation accuracy especially near the diaphragmatic region [1]. This study aims to systematically investigate the effect of breathing motion on lung shunt fraction (LSF), tumor-to-normal liver ratio (TNR), injected activity (IA) and absorbed dose estimation in 99mTc-MAA SPECT/CT for 90Y microsphere radioembolization treatment planning. Materials and Methods: The 4D extended cardiac torso (XCAT) phantom was used to simulate a phantom population of 72 phantoms, modelling 6 different anatomies, 2 TNRs (8.2 and 13), 2 tumor sizes (3.0 and 4.5 cm diameter), 4 tumor locations and 3 axial/anterior-posterior motion amplitudes of 1/0.6, 2/1.2 and 3/1.8 (cm), mimicking 99mTc-MAA distribution with LSF of 5%, 10% and 15%. Phantoms with no motion were also generated for reference. An analytical projector for low energy high resolution parallel-hole collimator was used to simulate 128 projections over 360o for SPECT, modeling attenuation, scatter and geometric collimator-detector-response (GCDR). The OS-EM algorithm was employed for image reconstruction with 4 iterations and 16 subsets with attenuation correction using averaged attenuation map, effective source scatter estimation and GCDR modelling. The volumes-of-interest (VOIs) for liver, lungs and tumor were mapped out from the reconstructed images based on the original phantom organ maps. The LSF, TNR, IA, absorbed dose of normal liver, tumor and lungs were calculated based on the measured counts from different VOIs and the partition model [2]. Results: Generally, along with the increase of breathing motion amplitude, the absolute errors of LSF, TNR, IA and absorbed dose increase. The LSF and lung dose are overestimated while TNR and tumor dose are underestimated due to the respiratory motion. Larger LSF errors associate with tumors located closer to the lung-liver interface while larger TNR errors associate with smaller tumor size and higher TNR due to respiration. For axial respiratory motion of 2 cm and LSF of 10%, the mean errors of LSF, TNR, IA, absorbed dose of normal liver, tumor and lungs are 69.8±8.2%, -27.0±7.1%, -12.7±10.4%, -2.3±2.5%, -28.6±8.3% and 69.8±8.2%, respectively. Conclusion: Respiration motion has a strong impact for 99mTc-MAA SPECT/CT based dosimetry and may change the patient management due to overestimation of LSF and underestimated IA may lead to under treatment. Further studies to minimize the impact of respiration on 99mTc-MAA SPECT/CT are warranted. References: [1] Bastiaannet R, et al. Medical Physics. 2017;44(10):5270-9. [2] Ho S, et al. Eur J Nucl Med. 1996;23(8):947-5.