Biological evaluation of ~(18)F-FDTP as a potential dopamine D_4 receptor PET imaging agent / 中华核医学杂志

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.

Effects of all-trans retinioic acid and tazarotene on MMP-1 and TIMP-1 expression in cultured human fibroblasts after heat shock / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanism of dermal damage in heat shock-induced skin aging by observing the expressions of metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) in retinoic acid-treated cultured human fibroblasts with heat shock.</p><p><b>METHODS</b>Cultured human fibroblasts were treated with tazarotene or all-trans-retinioic acid (at-RA) after heat shock for 30 min in 43 degrees celsius; water bath. Twenty-four hours later, MMP-1 and TIMP-1 contents in the supernatant of the cell culture medium were measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Both tazarotene and at-RA dose-dependently reduced the expression of MMP-1 and increased the expression of TIMP-1 in cultured human fibroblasts exposed to heat shock, and tazarotene produced stronger effect than at-RA.</p><p><b>CONCLUSION</b>Retinoic acid can reduce the expression of MMP-1 and increase the expression of TIMP-1 in cultured human fibroblasts, suggesting its therapeutic potential for heat shock-induced skin aging.</p>

188Re-labeled herceptin inhibits proliferation of breast cancer cell line SKBR-3 in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of (188)Re-labeled herceptin on the proliferation in vitro of breast carcinoma cell line (SKBR-3) overexpressing HER-2/neu proto-oncogene.</p><p><b>METHODS</b>Herceptin was radiolabeled with (188)Re through a direct labeling method. SKBR-3 cells were cultured with (188)Re-Herceptin at different radioactivity doses (3.7x10(4), 18.5x10(4), 37x10(4), 55.5x10(4) and 74x10(4) Bq/ml) or with (188)Re-nmIgG and (188)ReO(4)(-) for comparison. The cell proliferation inhibition was determined with MTT colorimetric assay.</p><p><b>RESULTS</b>(188)Re-Herceptin could markedly inhibit the growth of SKBR-3 cells in a radioactivity dose-dependent fashion, while the effect of (188)Re-nmIgG and (188)ReO(4)(-) showed rather poor inhibitory effect in vitro. The 50% inhibition doses (IC(50)) of (188)Re-Herceptin, (188)Re-nmIgG and (188)ReO(4)(-) were 76.1x10(4) Bq/L, 139.2x10(4) Bq/L and 175x10(4) Bq/L, respectively.</p><p><b>CONCLUSION</b>(188)Re-Herceptin can effectively inhibit the growth of in vitro cultured breast cancer cells overexpressing HER-2/neu, and shows much potential for clinical use in beast cancer radioimmunotherapy.</p>

Dopamine D(4) receptor antagonist 3-(4-[(18)F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one([(18)F]FMTP): radiosynthesis and in vivo characterization in rats.

We synthesized a novel (18)F-labeled dopamine D(4) receptor antagonist (Ki=4.3 nM), 3-(4-[(18)F]fluorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one ([(18)F]FMTP), which has exhibited high affinity and selectivity. Radiosyntheses were accomplished by the reaction of fluorine-18-labeled intermediate with 8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one (1) followed by HPLC purification. The overall radiochemical yield of the radiosynthesis was 19.5% (decay corrected), the specific radioactivity was about 110 GBq/micromol and the radiochemical purity was greater than 99%, the time of synthesis and purification was approximately 110 min. Tissue distribution studies of the [(18)F]FMTP in rats showed that the radioactivity in the brain was concentrated in frontal cortex and medulla, the region that has a high density of D(4) receptors. Pre-treatment with nonradioactive FMTP (1.0mg/kg) produced a significant reduction of radioactivity in all the regions. About 40% of total radioactivity in plasma and 100% in rat brain extract represented unchanged radioligand at 60 min after injection as determined by HPLC. These results indicate that [(18)F]FMTP have some specific binding to the D(4) receptor.