Metabolism and autoradiographic evaluation of [(18)F]FE@CIT: a Comparison with [(123)I]beta-CIT and [(123)I]FP-CIT.

PURPOSE: Since the late 1980s, cocaine analogues based on the phenyltropane structure, such as [(11)C]CFT and [(123)I]beta-CIT have been used for the imaging of the dopamine transporter. FE@CIT (fluoropropyl ester) and FP-CIT (N-fluoropropyl derivative) are further analogues. The aim of this study was to (1) evaluate and compare the metabolic stability of beta-CIT, FP-CIT and FE@CIT against carboxyl esterases and (2) evaluate selectivity of [(18)F]FE@CIT compared to [(123)I]beta-CIT and [(123)I]FP-CIT using autoradiography. METHODS: In vitro enzymatic hydrolysis assays were performed using different concentrations of beta-CIT, FE@CIT and FP-CIT with constant concentrations of carboxyl esterase. Autoradiography was performed on coronal 20-microm rat brain sections incubated with different radioactivity concentrations of [(123)I]beta-CIT, [(123)I]FP-CIT or [(18)F]FE@CIT and, additionally, with 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile [serotonin transporter (SERT)] and nisoxetine [norepinephrine transporter (NET)] for blocking experiments. RESULTS: In vitro assays showed Michaelis-Menten constants of 175 micromol (beta-CIT), 183 micromol (FE@CIT) and 521 micromol (FP-CIT). Limiting velocities were 0.1005 micromol/min (beta-CIT), 0.1418 micromol/min (FE@CIT) and 0.1308 micromol/min (FP-CIT). This indicates a significantly increased stability of FP-CIT, whereas carboxyl esterase stability of beta-CIT and FE@CIT showed no significant difference. Autoradiographic analyses revealed a good correlation between dopamine transporter (DAT)-rich regions and the uptake pattern of FE@CIT. Blocking experiments showed a higher DAT selectivity for [(18)F]FE@CIT than for the other two tracers. CONCLUSION: We found that (1) the metabolic stability of FE@CIT was comparable to that of beta-CIT, whereas FP-CIT showed higher resistance to enzymatic hydrolysis; and (2) the overall uptake pattern of [(18)F]FE@CIT on brain slices was comparable to that of [(123)I]beta-CIT and [(123)I]FPCIT. After blocking of NET and SERT binding, a significantly higher DAT selectivity was observed for [(18)F]FE@CIT. Hence, [(18)F]FE@CIT may be of interest for further clinical application.

Vascular endothelial growth factor in thyroid cyst fluids.

BACKGROUND: The pathogenesis of cystic thyroid nodules is incompletely understood. Based on the assumption that vascular endothelial growth factor (VEGF) may play an important role in the pathogenesis of thyroid cyst fluid, we investigated the VEGF concentration in cyst fluids of thyroid lesions. DESIGN: Cyst fluids from 24 patients (age 31-84 years) were obtained using ultrasound-guided fine-needle aspiration. The patients' cystic thyroid nodules were of different origins. METHODS: Thyroid and cyst volumes were determined using high-resolution ultrasonography. VEGF concentrations were determined using a solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: Differing elevated VEGF concentrations were demonstrated in cyst fluids of thyroid nodules of varied origins. The VEGF concentration in cyst fluid of patients with adenomatous goiter was significantly higher (P < 0.05) than that in thyroid nodules with cystic degeneration. The highest level of VEGF was found in bloody cyst fluid when compared with levels in other cyst fluids (P < 0.05). Interestingly, there was significant correlation (P < 0.01) between thyroid volume and VEGF concentration in cyst fluid, but no significant correlation (P = 0.20) between cyst volume and VEGF concentration. CONCLUSION: Significantly increased VEGF concentrations were found in bloody cyst fluid and in cyst fluid of thyroid adenomatous goiter, compared with VEGF concentrations in degenerative thyroid cysts. Our results suggest that VEGF may play an important role in the pathogenesis of thyroid cyst fluid.