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Synthesis and preliminary evaluation of a 99m Tc‐labeled folate‐ PAMAM dendrimer for FR imaging
Author(s) -
Song Manli,
Guo Zhide,
Gao Mengna,
Shi Changrong,
Xu Duo,
You Linyi,
Wu Xiaowei,
Su Xinhui,
Zhuang Rongqiang,
Pan Weimin,
Liu Ting,
Zhang Xianzhong
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12899
Subject(s) - dendrimer , chemistry , conjugate , in vivo , folate receptor , preclinical imaging , imaging agent , spect imaging , emission computed tomography , positron emission tomography , radiochemistry , nuclear chemistry , cancer cell , biochemistry , nuclear medicine , cancer , mathematical analysis , biology , medicine , mathematics , microbiology and biotechnology
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‐ HP 3 FA ) for FR imaging. The 99m Tc‐ HP 3 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‐ HP 3 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‐ HP 3 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‐ HP 3 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.