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First published online September 15, 2008, 10.2967/jnumed.108.054361
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Journal of Nuclear Medicine Vol. 49 No. 10 1701-1706
© 2008 by Society of Nuclear Medicine

doi: 10.2967/jnumed.108.054361

Basic Science Investigation

Whole-Body Evaluation of MIBG Tissue Extraction in a Mouse Model of Long-Lasting Type II Diabetes and Its Relationship with Norepinephrine Transport Protein Concentration

Claudia Kusmic1, Silvia Morbelli2, Cecilia Marini1, Marco Matteucci3, Chiara Cappellini3, Elena Pomposelli2, Paolo Marzullo1, Antonio L'Abbate1,3 and Gianmario Sambuceti2

1 Institute of Clinical Physiology CNR, Pisa, Italy 2 Department of Internal Medicine, Division of Nuclear Medicine, University of Genoa, Genova, Italy; and 3 Scuola Superiore Sant'Anna, Pisa, Italy

Correspondence: For correspondence or reprints contact: Claudia Kusmic, Area della Ricerca CNR, Istituto di Fisiologia Clinica, Via Moruzzi, 1-56124 Pisa, Italy. E-mail: kusmic{at}ifc.cnr.it

Accelerated cardiac washout of 123I-metaiodobenzylguanidine (MIBG), which is clinically used as an index of cardiac neuropathy in diabetes, is ascribed to decreased norepinephrine reuptake into synaptic vesicles. However, accelerated washout frequently contrasts with preserved early tracer uptake, whose significance remains undetermined. The aim of this study was to investigate in a mouse model of long-lasting type II diabetes whether the mismatch between MIBG early uptake and washout is the consequence of a more generalized disorder of the autonomic nervous system. Methods: Nine mice were given low doses of streptozotocin by intraperitoneal injection for 5 consecutive days. At 7 mo after streptozotocin, MIBG kinetics were evaluated by heart and liver time–activity curves and by tracer accumulation in the bladder. Data were compared with those obtained in 10 sham mice and correlated with the cardiac and hepatic tissue expression of norepinephrine transporter (NET) as assessed with a 3H-desipramine saturation binding assay. Results: In diabetic mice, myocardial and liver MIBG retention was reduced at 2 h and was associated with both increased tracer washout and reduced NET density. The rate of myocardial washout correlated with the degree of urinary MIBG excretion. Conclusion: The paradoxic observation of preserved early uptake associated with accelerated washout of MIBG in diabetes seems to be explained by a generalized disorder in NET function leading to reduced whole-body tracer removal from the blood and increased tracer availability for early myocardial uptake.

Key Words: type II diabetes • cardiac autonomic neuropathy • SPECT • radiobinding, mouse

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.


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