中文
Earlier issues
Announcement
More
Progress in Chemistry 2021, Vol. 33 Issue (3): 394-405 DOI: 10.7536/PC200571 Previous Articles   Next Articles

• Review •

Construction and Application of Dendrimer-Based SPECT Imaging Agent

Pingping Zhao1, Junxing Yang1, Jianhui Shi1, Jingyi Zhu1,*()   

  1. 1 School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China
  • Received: Revised: Online: Published:
  • Contact: Jingyi Zhu
  • Supported by:
    the National Natural Science Foundation of China(21807059); the Natural Science Foundation of Jiangsu Province(BK20180711); the Natural Science Foundation for Colleges and Universities in Jiangsu Province(17KJB350005); and the Postgraduate Research & Practice Innovation Program of Jiangsu Province(KYCX20_1122)
Richhtml ( 4 ) PDF ( 528 ) Cited
Export

EndNote

Ris

BibTeX

Dendrimer owns a precise chemical structure, including a small molecular core, an internal space induced by multiple branches, and large numbers of functional groups on the surface, which can be used to load a variety of nanoparticles and perform functional modification. In addition, based on the excellent properties of dendrimer, it demonstrates good biocompatibility and stability. After functional modification, it could achieve long blood circulation and high tissue specificity in vivo. Therefore, dendrimer has often been used as an ideal carrier for constructing SPECT imaging agents in recent years. Through multifunctional modification with various functional groups, the cytotoxicity of the generated nanocarrier is decreased and its accumulation at tumor site is improved, which faciliates accurate and efficient SPECT imaging. SPECT imaging monitors the physiological and pathological changes of lesions at the molecular level via monitoring the distribution, flow and metabolism of radionuclides in vivo. Compared with small molecular radionuclides, dendrimer-based SPECT imaging agents demonstrate longer circulation time and could achieve specific distribution after functional modification in vivo. In this review, various radionuclides labeled functional dendrimers are described in detail, their preparation methods and biomedical applications are summarized. Finally, the applications of these dendrimer-based SPECT imaging agents in the early diagnosis of tumor are prospected.

Key words: molecular imaging, nanoparticle-based contrast agents, dendrimer, SPECT imaging, biomedical application
Table 1 Radionuclides for SPECT imaging
Radionuclide 99mTc 111In 67Ga 201Tl 131I 125I
Emission type γ γ γ γ(81.7%)
β(89.9%) 		γ
Emission energy/keV 140 173, 247 93, 184, 300, 393 135~167 284, 364, 606 27.4~35.4
Half-life 6 h 2.83 d 78.3 h 74 h 8.01 d 60 d
Fig.1 Schematic representation of the dendrimer structure
Fig.2 Schematic representation of the nanostructure(a) and the synthesis procedure(b) of99mTc-Au-Ac DENPs and99mTc-Au-Gly DENPs[34]
Fig.3 SPECT/CT images of tumors(a and b), SPECT signal intensity of tumors(c), and SPECT signal ratio(tumor/muscle)(d) after intravenous injection of the {(Au0)6-G2-DTPA(99mTc)-PEG-FA} DENPs(a) and {(Au0)6-G2-DTPA(99mTc)-mPEG} DENPs(b) at different time points postinjection[35]
Fig.4 SPECT images(a) and tumor relative signal intensities(b) of the nude mice bearing C6 xenografted tumors after 3 days of DOX treatment at different time points post-intravenous injection of the99mTc-duramycin-Au DENPs or 99mTc-Au DENPs. SPECT images of ex vivo tumors at 8 h post-injection(c)[36]
Fig.5 Biodistribution of G1-[111In(do3a-pyNO-C)](A) and G4-[111In(do3a-pyNO-C)](B) in rats[37]
Fig.6 Structures of the PAMAM(G1.5, 2), DAB(G3.5), DAE(G2), and CSi-PEO(G1) dendrimers[39]
Fig.7 Schematic illustration of the synthesis of the131I-G5.NHAc-HPAO-PEG-FA[41]
Fig.8 SPECT images(A), SPECT images of ex vivo tumors(B) and the relative SPECT signal intensities(C) of C6 xenografts tumors at different time points post injection of 131I-G5.NHAc-HPAO-(PEG-BmK CT)-(mPEG) and 131I-G5.NHAc-HPAO-(PEG-MAL)-(mPEG)[42]
Fig.9 The tumor volume growth curve of C6 xenografts tumors mice treated with different reagents[42]
[1]
Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O. Cancer Cell., 2009, 15:220.
[2]
Miller K D, Siegel R L, Lin C C, Mariotto A B, Kramer J L, Rowland J H, Stein K D, Alteri R, Jemal A. CA: A Cancer J. Clin., 2016, 66(4):271.
[3]
Mirzaei H, Sahebkar A, Jaafari M R, Goodarzi M, Mirzaei H R. J. Cell. Physiol., 2017, 232(12):3251.
[4]
Miller K D, Nogueira L, Mariotto A B, Rowland J H, Yabroff K R, Alfano C M, Jemal A, Kramer J L, Siegel R L. CA: A Cancer J. Clin., 2019, 69(5):363.
[5]
Collins M S, Miranda R N, Medeiros L J, de Meneses, M P S, Iyer S P, Butler C E, Liu J, Clemens M W. Plast. Reconstr. Surg., 2019, 143:41S.
[6]
Keshavarzi M, Darijani M, Momeni F, Moradi P, Ebrahimnejad H, Masoudifar A, Mirzaei H. J. Cell. Biochem., 2017, 118(10):3055.
[7]
Pomper M G. Acad. Radiol., 2001, 8(11):1141.
[8]
Saadatpour Z, Bjorklund G, Chirumbolo S, Alimohammadi M, Ehsani H, Ebrahiminejad H, Pourghadamyari H, Baghaei B, Mirzaei H R, Sahebkar A, Mirzaei H, Keshavarzi M. Cancer Gene Ther., 2016:1.
[9]
Hyun H, Cho C S. Tissue Eng. Regen. Med., 2019, 16(5):431.
[10]
Michno W, Wehrli P M, Blennow K, Zetterberg H, Hanrieder J. J. Neurochem., 2019, 151(4):488.
[11]
Qiao Z, Shi X. Prog. Polym. Sci., 2015, 44:1.
[12]
Zhu J Y, Wang G Y, Alves C S, Tomás H, Xiong Z J, Shen M W, Rodrigues J, Shi X Y. Langmuir, 2018, 34(41):12428.
[13]
Yu P Q, Lei Y G, Hu H F, Deng H Y, Zhang W X. Spectrochimica Acta Part A: Mol. Biomol. Spectrosc., 2019, 213:330.
[14]
Mekuria S L, Debele T A, Tsai H C. RSC Adv., 2016, 6(68):63761.
[15]
Bowen S R, Yuh W T C, Hippe D S, Wu W, Partridge S C, Elias S, Jia G, Huang Z B, Sandison G A, Nelson D, Knopp M V, Lo S S, Kinahan P E, Mayr N A. J. Magn. Reson. Imaging, 2018, 47(5):1388.
[16]
Badea C T, Clark D P, Holbrook M, Srivastava M, Mowery Y, Ghaghada K B. Phys. Med. Biol., 2019, 64(6):065007.
[17]
Karrer T M, McLaughlin C L, Guaglianone C P, Samanez-Larkin G R. Neurobiol. Aging., 2019, 80:1.
[18]
Iacovacci V, Blanc A, Huang H W, Ricotti L, Schibli R, Menciassi A, Behe M, PanÉ S, Nelson B J. Small, 2019, 15(34):1900709.
[19]
Lee S B, Singh T D, Oh S G, Ahn S, Yoon S, Lee S W, Jeong S Y, Ahn B C, Lim D K, Jeon Y H. J. Nucl. Med., 2016, 57:1143.
[20]
Penner N, Xu L, Prakash C. Chem. Res. Toxicol., 2012, 25(3):513.
[21]
Kassis A I, Adelstein S J. J. Nucl. Med., 2005, 46:4S.
[22]
Parrott M C, Benhabbour S R, Saab C, Lemon J A, Parker S, Valliant J F, Adronov A. J. Am. Chem. Soc., 2009, 131(8):2906.
[23]
Ghobril C, Lamanna G, Kueny-Stotz M, Garofalo A, Billotey C, Felder-Flesch D. New J. Chem., 2012, 36(2):310.
[24]
Kim Y H, Jeon J, Hong S H, Rhim W K, Lee Y S, Youn H, Chung J K, Lee M C, Lee D S, Kang K W, Nam J M. Small, 2011, 7(14):2052.
[25]
Ahmed S, Dong J H, Yui M, Kato T, Lee J, Park E Y. J. Nanobiotechnology, 2013, 11(1):28.
[26]
Lewis M R, Kannan R. Wires Nanomed. Nanobi, 2014, 6(6):628.
[27]
Huang X L, Zhang F, Lee S, Swierczewska M, Kiesewetter D O, Lang L X, Zhang G F, Zhu L, Gao H K, Choi H S, Niu G, Chen X Y. Biomaterials, 2012, 33(17):4370.
[28]
Zhao L Z, Wen S H, Zhu M L, Li D, Xing Y, Shen M W, Shi X Y, Zhao J H. Artif. Cells Nanomed. Biotechnol., 2018, 46(sup1):488.
[29]
Hahn M A, Singh A K, Sharma P, Brown S C, Moudgil B M. Anal. Bioanal. Chem., 2011, 399(1):3.
[30]
Wang Y, Guo R, Cao X Y, Shen M W, Shi X Y. Biomaterials, 2011, 32(12):3322.
[31]
Kojima C, Umeda Y, Ogawa M, Harada A, Magata Y, Kono K. Nanotechnology, 2010, 21(24):245104.
[32]
Gross M. Chem. World., 2007, 4:62.
[33]
Agashe H B, Babbar A K, Jain S, Sharma R K, Mishra A K, Asthana A, Garg M, Dutta T, Jain N K. Nanomed.: Nanotechnol. Biol. Med., 2007, 3(2):120.
[34]
Wen S H, Zhao L Z, Zhao Q H, Li D, Liu C C, Yu Z B, Shen M W, Majoral J P, Mignani S, Zhao J H, Shi X Y. J. Mater. Chem. B, 2017, 5(21):3810.
[35]
Li X, Xiong Z G, Xu X Y, Luo Y, Peng C, Shen M W, Shi X Y. ACS Appl. Mater. Interfaces, 2016, 8(31):19883.
[36]
Xing Y, Zhu J Y, Zhao L Z, Xiong Z J, Li Y J, Wu S, Chand G, Shi X Y, Zhao J H. Drug Deliv., 2018, 25(1):1384.
[37]
Biricová V, Lázniková A, Lázní ek M, Polášek M, Hermann P. J. Pharm. Biomed. Anal., 2011, 56(3):505.
[38]
Kobayashi H, Wu C C, Kim M K, Paik C H, Carrasquillo J A, Brechbiel M W. Bioconjugate Chem., 1999, 10(1):103.
[39]
Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener J W, Meijer E W, Paulus W, Duncan R. J. Control. Release, 2000, 65(1/2):133.
[40]
Wiwattanapatapee R, Carreño-GÓmez B, Malik N, Duncan R. Pharm. Res., 2000, 17(8):991.
[41]
Zhu J Y, Zhao L Z, Cheng Y J, Xiong Z J, Tang Y Q, Shen M W, Zhao J H, Shi X Y. Nanoscale, 2015, 7(43):18169.
[42]
Cheng Y, Zhu J, Zhao L, Xiong Z, Tang Y, Liu C, Guo L, Qiao W, Shi X, Zhao J. Nanomedicine., 2016, 11:1253.
[43]
Fu Y J, Yin L T, Liang A H, Zhang C F, Wang W, Chai B F, Yang J Y, Fan X J. Neurosci. Lett., 2007, 412(1):62.
[44]
Fan S Z, Sun Z B, Jiang D H, Dai C, Ma Y B, Zhao Z H, Liu H, Wu Y L, Cao Z J, Li W X. Cancer Lett., 2010, 291(2):158.
[45]
Fu Y J, An N, Chan K G, Wu Y B, Zheng S H, Liang A H. Biotechnol. Lett., 2011, 33(7):1309.
[46]
Zhao L Z, Zhu J Y, Cheng Y J, Xiong Z J, Tang Y Q, Guo L L, Shi X Y, Zhao J H. ACS Appl. Mater. Interfaces, 2015, 7(35):19798.
[1] Xuedan Qian, Weijiang Yu, Junzhe Fu, Youxiang Wang, Jian Ji. Fabrication and Biomedical Application of Hyaluronic Acid Based Micro- and Nanogels [J]. Progress in Chemistry, 2023, 35(4): 519-525.
[2] Xueer Cai, Meiling Jian, Shaohong Zhou, Zefeng Wang, Kemin Wang, Jianbo Liu. Chemical Construction of Artificial Cells and Their Biomedical Applications [J]. Progress in Chemistry, 2022, 34(11): 2462-2475.
[3] Zixuan Wang, Yuefei Wang, Wei Qi, Rongxin Su, Zhimin He. Design, Self-Assembly and Application of DNA-Peptide Hybrid Molecules [J]. Progress in Chemistry, 2020, 32(6): 687-697.
[4] Qiangqiang Hu, Heze Guo, Hongjing Dou. Size Control and Biomedical Applications of ZIF-8 Nanoparticles [J]. Progress in Chemistry, 2020, 32(5): 656-664.
[5] Tianyou Chen, Zihao Wang, Zizheng Xu, Zushun Xu, Zheng Cao. Synthesis and Applications of Dendrimer-Based Inorganic Nanoparticles [J]. Progress in Chemistry, 2020, 32(2/3): 249-261.
[6] Xiaofu Wu, Hui Tong, Lixiang Wang. Fluorescent Polymer Materials for Detection of Explosives [J]. Progress in Chemistry, 2019, 31(11): 1509-1527.
[7] Xiao Xiao, Changsheng Chen, Weiqiang Liu, Yeshun Zhang. Structure, Features and Biomedical Applications of Silk Sericin [J]. Progress in Chemistry, 2017, 29(5): 513-523.
[8] Du Xin, Zhao Caixia, Huang Hongwei, Wen Yongqiang, Zhang Xueji. Synthesis of Dendrimer-Like Porous Silica Nanoparticles and Their Applications in Advanced Carrier [J]. Progress in Chemistry, 2016, 28(8): 1131-1147.
[9] Liu Yingya, Fan Xiao, Li Yanyan, Qu Lulu, Qin Haiyue, Cao Yingnan, Li Haitao. Multispectral Photoacoustic Tomography and Its Development in Biomedical Application [J]. Progress in Chemistry, 2015, 27(10): 1459-1469.
[10] Song Lifeng, Zhao Jin, Yuan Xiaoyan. Strengthening of Hydrogels Based on Polysaccharide and Polypeptide [J]. Progress in Chemistry, 2014, 26(0203): 385-393.
[11] Li Tian, Wang Yilong, Guo Fangfang, Shi Donglu. Synthesis and Biomedical Applications of Magnetic Nanocomposites with Complex Morphologies [J]. Progress in Chemistry, 2013, 25(12): 2053-2067.
[12] Zhang Xiacong, Li Wen, Zhang Afang. Thermoresponsive Dendritic Polymers [J]. Progress in Chemistry, 2012, (9): 1765-1775.
[13] Dong Bo, Yan Xibo, Niu Yujie, Wang Xin, Wang Lianyong, Wang Yanming* . Functionalized Polyamidoamine Dendrimer as Gene Delivery Vectors [J]. Progress in Chemistry, 2012, 24(12): 2352-2358.
[14] Yao Min, Wang Jiajun, Gu Xueping, Feng Lianfang. Synthesis and Application of Dendrimers Based on Polyhedral Oligomeric Silsesquioxanes [J]. Progress in Chemistry, 2012, 24(0203): 405-413.
[15] Dong Haiqing, Li Yongyong, Li Lan, Shi Donglu. Cyclodextrins/Polymer Based (Pseudo)Polyrotaxanes for Biomedical Applications [J]. Progress in Chemistry, 2011, 23(5): 914-922.