RT Journal Article
SR Electronic
T1 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
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1701
OP 1706
DO 10.2967/jnumed.108.054361
VO 49
IS 10
A1 Kusmic, Claudia
A1 Morbelli, Silvia
A1 Marini, Cecilia
A1 Matteucci, Marco
A1 Cappellini, Chiara
A1 Pomposelli, Elena
A1 Marzullo, Paolo
A1 L'Abbate, Antonio
A1 Sambuceti, Gianmario
YR 2008
UL http://jnm.snmjournals.org/content/49/10/1701.abstract
AB 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.