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Synthesis and preliminary evaluation of a 99m Tc-labeled folate-PAMAM dendrimer for FR imaging.
Chemical Biology & Drug Design 2017 May
Folate receptor is an ideal target for tumor-specific diagnostic and therapeutic. The aim of this study was to synthesize 99m Tc-labeled folate-polyamidoamine dendrimer modified with 2-hydrazinonicotinic acid (99m Tc-HP3 FA) for FR imaging. The 99m Tc-HP3 FA conjugate was prepared using N-tris-(hydroxymethyl)-methylglycine and trisodium triphenylphosphine-3,3',3″-trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro-single-photon emission computed tomography/CT imaging were performed. The radiolabeled 99m Tc-HP3 FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP = -1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR-abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro-single-photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR-overexpressed KB tumor, and the tumor-to-muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of 99m Tc-HP3 FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of 99m Tc-HP3 FA for early diagnosis of FR-positive tumors with non-invasive single-photon emission computed tomography imaging was demonstrated and the possibility of imaging-guided drug delivery based on multifunctional polyamidoamine will be studied in the future.
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