Preparation and pharmacological characterization of [76Br]-meta-bromobenzylguanidine ([76Br]MBBG).
[76Br]-meta-Bromobenzylguanidine ([76Br]MBBG) was prepared from the iodinated analog (MIBG) and [76Br]NH4 using a Cu(+)-assisted halogen exchange reaction. [76Br]MBBG was produced in a 60-65% radiochemical yield with a specific activity of 20 MBq/nmol. In rats, biodistribution kinetic studies showed a high uptake of [76Br]MBBG in heart tissues with its maximum of 5% ID/S at 2 h p.i.; whereas 4 h p.i., the maximum of the heart-to-lung concentration ratio of 8 was observed. Metabolic studies in rats indicated that [76Br]MBBG was rapidly metabolized in plasma. However in heart tissue, 25 h p.i., 85% of the radioactivity still represented unchanged radiotracer. Pharmacological studies in rats showed that the myocardial uptake of [76Br]MBBG was similar to that of norepinephrine. After pretreatment of the rats, the uptake of [76Br]MBBG was reduced 4 h p.i. to the following values: after desipramine (DMI) to 37%, after dexamethasone (DXM) to 88% and after 6-hydroxydopamine (6-OHDA) to 16%. These preliminary results suggest that [76Br]MBBG can be useful for the assessment of heart catecholamine reuptake disorders with PET.
Loc'h
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C
Service Hospitalier Frédéric Joliot, DRIPP, DSV-CEA, Orsay, France.
Mardon
K
K
Valette
H
H
Brutesco
C
C
Merlet
P
P
Syrota
A
A
Maziere
B
B
D000818:Animals; D001967:Bromine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D001969:Bromobenzenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D003891:Desipramine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution
D001967:Bromine Radioisotopes; D001969:Bromobenzenes; D006146:Guanidines; C083603:3-bromobenzylguanidine; D003907:Dexamethasone; D016627:Oxidopamine; D003891:Desipramine