The aim of this retrospective study was to compare the heart-to-mediastinum ratio (HMR) of123I-metaiodobenzylguanidine (123I-MIBG) uptake obtained using a multipinhole cadmium-zinc-telluride (CZT) camera with that obtained using conventional planar imaging.Methods:Forty consecutive heart failure patients underwent planar acquisition 4 h after123I-MIBG injection (191 ± 41 [mean ± SD] MBq). To localize the heart using the CZT camera,99mTc-tetrofosmin (358 ± 177 MBq) was administered and dual-isotope acquisition was performed. The HMRs were calculated with conventional planar imaging (HMRplanar), with anterior reprojection images using the CZT camera (HMRreproj), and with transaxial reconstructed images using the CZT camera (HMRtransaxial). In a phantom study, we estimated a linear model fitting the CZT camera data to the planar data, and we applied it to provide corrected CZT camera-determined HMRs in patients (cHMRreprojand cHMRtransaxial).Results:Thirty-four men and 6 women (71 ± 9 y old) with ischemic (22 patients) and nonischemic (18 patients) heart failure completed the study. For 22 of the 40 patients (55%), the New York Heart Association classification was class II and the ejection fraction was 35% ± 9%. HMRreproj(1.12 ± 0.19) and HMRtransaxial(1.35 ± 0.34) were lower than HMRplanar(1.44 ± 0.14) (P< 0.0001 andP< 0.01, respectively). cHMRreproj(1.54 ± 0.09) and cHMRtransaxial(1.45 ± 0.14) were significantly different (P< 0.0001). Lin concordance correlation and Bland-Altman analysis demonstrated an almost perfect concordance and a high agreement between HMRplanarand cHMRtransaxial(Pwas not significant) but not between HMRplanarand cHMRreproj(P< 0.0001).Conclusion:This study demonstrated that determination of the late HMR of cardiac123I-MIBG uptake using dual-isotope (123I and99mTc) acquisition on a multipinhole CZT camera was feasible in patients with heart failure. However, this determination should be performed using transaxial reconstructed images and linear correction based on phantom data acquisitions.