title: 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.
abstract: 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.
authors.affiliation: Institute of Clinical Physiology CNR, Pisa, Italy. kusmic@ifc.cnr.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Kusmic
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marini
authors.forename: Marco
authors.initials: M
authors.lastname: Matteucci
authors.forename: Chiara
authors.initials: C
authors.lastname: Cappellini
authors.forename: Elena
authors.initials: E
authors.lastname: Pomposelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Marzullo
authors.forename: Antonio
authors.initials: A
authors.lastname: L'abbate
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
mesh_terms: 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
chemical_list: D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine