Radiolabelled metaiodobenzylguanidine (MIBG), a monoamine uptake and storage tracer, is used for the scintigraphic detection of tumors deriving from the neural crest 1, 2 as well as for assessing the functional status of the sympathetic nerve endings i

Radiolabelled metaiodobenzylguanidine (MIBG), a monoamine uptake and storage tracer, is used for the scintigraphic detection of tumors deriving from the neural crest [1,2] as well as for assessing the functional status of the sympathetic nerve endings in the human heart and lungs [3, 4]. While there have been several publications dealing with the clinical applications of this tracer, less is known about the mechanisms underlying its uptake by noradrenergic nerve endings; moreover the findings that have emerged from the few studies that have been conducted are often discordant, in part due to the different experimental models used [5-9]. A greater understanding of the mechanisms underlying the uptake of this tracer is essential since a number of controversial issues recently emerged, especially in cardiac studies: (1) the frequent uptake abnormalities in normal subjects [10-12]; (2) the unclear interference of various drugs [4,13-14]; (3) the influence of the specific activity of the tracer preparation on cardiac scintigraphies [15-17]. Indeed the pharmacokinetic behaviour of MIBG in humans depends not only on the specific uptake by noradrenergic neurons (which forms the basis for its use in scintigraphic studies), but also on the non-specific neuronal uptake and non-neuronal uptake [18-20]. A selective model is needed, one capable of focusing exclusively on the true specific carrier-mediated uptake mechanism by sympathetic nerve terminals in order to better understand the pharmacokinetic behaviour of MIBG, as compared to noradrenaline (NA), and to study in-vitro the effects of the presence and degree of pharmacologic interaction of various drugs on the MIBG uptake. Synaptosomes are nerve terminals isolated from rat cerebral cortex; they are a well validated in-vitro pharmacokinetic model [21-22]. In this study we aimed at verifying the feasibility of the use of synaptosomes as an in-vitro model for studying MIBG specific uptake and at evaluating the uptake analogies of MIBG and NA in neuroadrenergic tissues by examining the ability of MIBG to inhibit the uptake of’ NA. On the other hand an in-vivo model is also needed in order to confirm in-vitro data and to provide more convincing evidence of the interference of medical therapies currently delivered to patients with cardiac diseases. To this aim in this study we used Wistar rats and we verified the possibility: 1) to image the rats heart by standard nuclear medicine imaging equipment using 123I-MIBG (tracer of the adrenergic terminals) and 201Thallium (tracer of myocardial perfusion); 2) to obtain quantitative data on the MIBG uptake under baseline conditions and under pharmacologic challenge.