Meta-iodobenzylguanidine (MIBG) is an analog of guanethidine, an adrenergic blocking agent. Its uptake and storage mechanism is similar to that of noradrenaline (also known as norepinephrine) [1, 2]. It is actively taken up by postganglionic presynaptic nerve endings in the adrenergic nervous system, using an energy-dependent noradrenaline transporter mechanism. MIBG is also actively taken up by noradrenaline vesicles and the ATPase-dependent proton pump via a vesicle monoamine transporter [3–5]. Therefore, we can perform noninvasive assessment of the pathophysiology of organs that are innervated by the sympathetic nervous system by using this agent. Noradrenaline and MIBG kinetics in the sympathetic nervous system are described in Chap. 13.

In 1980, the tissue distributions of three kinds of radiolabeled iodobenzylguanidine (e.g., ¹²⁵I-meta-, ¹²⁵I-para-, and ¹³¹I-para-iodobenzylguanidine) were determined in dogs by Wieland et al. for the first time [1]. The high affinity and retention of these agents were observed in the adrenal medulla; high myocardial concentrations were also observed at early time intervals. Images of the adrenal medullae were obtained with ¹³¹I-para-iodobenzylguanidine. In 1981, ¹²³I-MIBG was used to image the heart in five normal men [6]. The left ventricle was visualized 1–2 min after MIBG injection. The mean cardiac uptake was 0.63 % of the injected dose after 5 min and 0.76 % at 2 h. In 1988, ¹²³I-MIBG cardiac scintigraphy was used in patients with idiopathic congestive cardiomyopathy and myocardial infarctions to determine the function and damage of the cardiac sympathetic nerve endings [7, 8]. Since then, this imaging tool has been further developed to evaluate various kinds of heart disease, such as heart failure, ischemic heart disease, and cardiomyopathy. A detailed history of MIBG development is described in Chap. 13. Technical considerations for MIBG cardiac scintigraphy are described in the Chap. 14. Findings using MIBG cardiac scintigraphy in cardiac diseases, diabetes mellitus (DM), and other disorders are described in Chap. 15.

In Japan in 1987, the Daiichi Radioisotope Laboratory (currently, the FUJIFILM RI Pharma Co., Ltd.) performed a multicenter clinical trial of ¹²³I-MIBG (named MyoMIBG) to image the heart. In 1991, the results of this multicenter clinical trial using ¹²³I-MIBG were reported [9]. In 1992, the Japanese Ministry of Welfare (currently known as the Ministry of Health, Labor and Welfare) approved the clinical use of ¹²³I-MIBG in cardiology practice. Since then, we have accumulated extensive clinical experience dealing with various heart diseases, including ischemic heart disease, arrhythmia, idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, and cardiomyopathies secondary to DM, renal failure, and other metabolic disorders. In 1994, ¹²³I-MIBG cardiac scintigraphy was applied to patients with neurological disorders, such as Parkinson’s disease (PD) and familial amyloidotic neuropathy, to assess systemic autonomic dysfunction for the first time [10, 11]. Reduced cardiac MIBG uptake was observed in patients with PD, not only with orthostatic hypotension (OH) but also without OH [10]. Seki reported on a patient with PD with reduced cardiac MIBG uptake and the possible usefulness of ¹²³I-MIBG cardiac scintigraphy to evaluate disturbances in the sympathetic nervous system in PD [12]. Yoshita and Orimo reported that cardiac MIBG uptake was reduced in PD [13, 14] and that the degree of reduced cardiac MIBG uptake correlated with motor symptom severity [14]. After these reports, research focusing on ¹²³I-MIBG cardiac scintigraphy in PD progressed in Japan and Europe. Many studies have reported that this imaging tool is useful to differentiate PD from other types of parkinsonism, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and vascular parkinsonism together with essential tremor. Goldstein reported that reduced cardiac fluorodopamine uptake was observed in PD, but not in MSA, using positron emission tomography with ¹⁸F-fluorodopamine [15]. In 2001, Watanabe and Yoshita reported that cardiac MIBG uptake was reduced in dementia with Lewy bodies (DLB) and that ¹²³I-MIBG cardiac scintigraphy was a useful tool to differentiate DLB from AD [16, 17]. Findings from MIBG cardiac scintigraphy in PD and related disorders and DLB and related dementia are described in Chaps. 15 and 16, respectively. The physiological background of reduced cardiac MIBG uptake is described in Chap. 17.