Synthesis and preliminary evaluation of a 99mTc‐labeled folate‐PAMAM dendrimer for FR imaging. (2nd December 2016)

• Record Type: Journal Article
• Authors: Song, Manli; Guo, Zhide; Gao, Mengna; Shi, Changrong; Xu, Duo; You, Linyi; Wu, Xiaowei; Su, Xinhui; Zhuang, Rongqiang; Pan, Weimin; Liu, Ting; Zhang, Xianzhong
• Is Part Of: Chemical biology & drug design. Volume 89:Number 5(2017)
• Page Start: 755
• Page End: 761
• Publication Date: 2016-12-02
• Subjects: folate receptor -- KB tumor‐bearing mice -- PAMAM dendrimer -- SPECT imaging -- technetium‐99m; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12899
• Languages: English
• ISSNs: 1747-0277

Abstract

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 (log P = −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. Abstract : A FA‐conjugated PAMAM dendrimer was synthesized and radiolabeled with 99m Tc successfully. Our results show that this folate‐PAMAM dendrimer has the potential as a non‐invasive radioactive diagnostic imaging agent for the detection of FR‐positive cancers. Furthermore, this versatile strategy can be extended to sensitive multimodal imaging and/or enhanced therapy of different cancers.