Synthesis and preliminary evaluation of a 99m Tc-labeled folate-PAMAM dendrimer for FR imaging.

Abstract

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.

• Authors: Manli Song, Zhide Guo, Mengna Gao, Changrong Shi, Duo Xu, Linyi You, Xiaowei Wu, Xinhui Su, Rongqiang Zhuang, Weimin Pan, Ting Liu, Xianzhong Zhang
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 89 Issue 5 Pg. 755-761 (05 2017) ISSN: 1747-0285 [Electronic] England
• PMID: 27910223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons A/S.

Chemical References

• Dendrimers
• PAMAM Starburst
• Radiopharmaceuticals
• Technetium
• Folic Acid

Topics

• Animals
• Cell Line, Tumor
• Dendrimers (chemistry)
• Folic Acid (chemistry)
• Humans
• Mice
• Mice, Inbred BALB C
• Neoplasms (diagnostic imaging)
• Radiopharmaceuticals (chemical synthesis, chemistry)
• Technetium (chemistry)
• Tomography, Emission-Computed, Single-Photon
• Tomography, X-Ray Computed
• Transplantation, Heterologous