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- W146793954 abstract "In the past funding period we have concentrated in developing new 99mTc labeled MIBG analogs. Basic chemistry of ligand synthesis, radiochemistry of Re and 99mTc complex formation, separation of stereoisomers and in vitro stability were investigated. We have prepared a number of new MIBG derivatives containing chelating moiety N2S2 and additional groups to increase lipophilicity. Unfortunately none of the new 99mTc labeled MIBG analogs showed promise as an imaging agent for myocardial neuronal function. Radioactive-iodine-labeled meta-iodobenzylguanidine (MIBG) is currently being used as an in vivo imaging agent to evaluate neuroendocrine tumors as well as the myocardial sympathetic nervous system in patients with myocardial infarct and cardiomyopathy. It is generally accepted that MIBG is an analog of norepinephrine and its uptake in the heart corresponds to the distribution of norepinephrine and the density of sympathetic neurons. A series of MIBG derivatives containing suitable chelating functional groups N2S2 for the formation of [Tcv0]+3N2S2 complex was successfully synthesized and the 99mTc-labeled complexes were prepared and tested in rats. One of the compounds, [99mTc]M2, tested showed significant, albeit lower, heart uptakes post iv injection in rats (0.18% dose/organ at 4 hours) as compared to [l25l]MIBG (1.4% dose/organ at 4 hours). The heart uptake of the 99mTc-labeled complex, [99mTc]M2, appears to be specific and can be reduced by coinjection with nonradioactive MIBG or by pretreatment with desipramine. a selective norepinephrine transporter inhibitor. Further evaluation of the in vitro uptake of [99mTc]M2 in cultured neuroblastoma cells displayed consistently lower, but measurable uptake (app. 10% of that for [125l]MlBG). These preliminary results suggested that the mechanisms of heart uptake of [99mTc]M2 may be related to those for [125l]MIBG uptake. To improve the heart uptake of the MIBG derivatives we have developed chemistry related to the preparation of new ligands, M4 and M5. The radiolabeling was successful, but the biodistribution of the new MIBG derivatives did not show any improvements in heart uptake. Our effort in this area has met with only limited success. Unfortunately, the new [99mTc]labeled MIBG derivatives showed lower uptake in the heart in biodistribution study." @default.
- W146793954 created "2016-06-24" @default.
- W146793954 creator A5022390942 @default.
- W146793954 date "2003-02-25" @default.
- W146793954 modified "2023-09-24" @default.
- W146793954 title "Receptor Specific Ligands for Spect Imaging" @default.
- W146793954 doi "https://doi.org/10.2172/836898" @default.
- W146793954 hasPublicationYear "2003" @default.
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