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.
Accelerated cardiac washout of (123)I-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 (3)H-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.


CONCLUSIONS
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.
Kusmic
Claudia
C
Institute of Clinical Physiology CNR, Pisa, Italy. kusmic@ifc.cnr.it
Morbelli
Silvia
S
Marini
Cecilia
C
Matteucci
Marco
M
Cappellini
Chiara
C
Pomposelli
Elena
E
Marzullo
Paolo
P
L'abbate
Antonio
A
Sambuceti
Gianmario
G
D019797:3-Iodobenzylguanidine / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine