An improved kit formulation of a dopamine transporter imaging agent: [Tc-99m]TRODAT-1

Recently, [Tc-99m]TRODAT-1, the first Tc-99m-labeled tracer for imaging CNS dopamine transporters in humans, was reported. This tracer displayed excel lent specific binding to dopamine transporters in the basal ganglia region of the brain, thus it is potentially useful for the diagnosis of deficit of dopamine transporters in neurodegenerative diseases, such as Parkinson's d isease. Preparation of [Tc-99m]TRODAT-1 was previously achieved by a multis tep kit formulation. It is highly desirable to further improve the preparat ion by developing a simplified one-vial formulation with a reduced amount o f TRODAT-1 ligand for routine clinical use. To achieve this goal, a series of studies to optimize labeling efficiency by varying a combination of fact ors (amount of free ligand, reaction reagents, and reaction pH) was carried out. [Tc-99m]TRODAT-1 prepared by this new kit formulation was evaluated b y assessing the brain uptake and target (striatum) versus nontarget (cerebe llum) ratios in rats. Appropriate amounts of various ingredients for a one- vial kit formulation providing greater than or equal to 90% radiolabeling y ields were identified. The most consistent and reliable formulation contain ed 10 mu g of TRODAT-1 (a reduction of free ligand from 200 mu g to 10 mu g ), 32 mu g of SnCl2, 10 mg of sodium glucoheptonate, and 840 mu g of disodi um EDTA in one vial as a lyophilized kit. It is feasible to reconstitute th e vial with [Tc-99m]pertechnetate (0.5-2 mL, less than or equal to 1110 MBq , 30 mCi), resulting in a final solution with a pH value of 4.5-5.0. [Tc-99 m]TRODAT-1, prepared by this new kit, was stable at room temperature for 6 h. Biodistribution studies of this agent in rats with the new formulation s howed similar regional brain distribution as compared with those obtained w ith the previous preparation (high striatum-to-cerebellum ratio). In conclu sion, using this lyophilized one-vial kit formulation, [Tc-99m]TRODAT-1 can be prepared with greater than 90% radiochemical purity. This simplified ki t will significantly improve the reliability of preparation of this agent f or routine clinical use. NUCL MED BIOL 26;4: 461-4661 1999. (C) 1999 Elsevi er Science Inc. All rights reserved.