Gansu Academy of Medical science and Gansu Provincial Tumor Hospital

Lanzhou, China

Gansu Academy of Medical science and Gansu Provincial Tumor Hospital

Lanzhou, China
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Yuan J.-C.,Northwest Normal University | Miao C.-P.,Northwest Normal University | Zeng X.-W.,Gansu Academy of Medical science and Gansu Provincial Tumor Hospital | Guo H.-Y.,Gansu Academy of Medical science and Gansu Provincial Tumor Hospital | And 3 more authors.
Chemical Research in Chinese Universities | Year: 2013

To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly(HPMA)-APMA-DTPA[HPMA=N-(2-hydroxypropyl) methacrylamide; APMA=N-(3-aminopropyl)methacrylamide; DTPA=diethylenetriaminepentaacetic acid] was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N′-azobis(isobutyronitrile) as the initiator. The copolymers were characterized with nuclear magnetic resonance(NMR) spectroscopy and gel permeation chromatography(GPC, M n=2.2×104, M w/M n=1.38). Subsequently, poly(HPMA)-APMA-DTPA was conjugated with 99mTc radionuclide. Prolonged retention of poly(HPMA)-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography(SPECT-CT) at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly(HPMA)-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans. © 2013 Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH.


Yuan J.,Northwest Normal University | Yuan B.,Northwest Normal University | Guo H.,Gansu Academy of Medical science and Gansu Provincial Tumor Hospital | Zeng X.,Gansu Academy of Medical science and Gansu Provincial Tumor Hospital | And 6 more authors.
Journal of Biomaterials Science, Polymer Edition | Year: 2013

Human hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific sulfapyridine HPMA (HPMA: N-(2-hydroxypropyl methacrylamide)) copolymer (sulfapyridine: SPD) conjugates, nonspecific HPMA copolymer conjugates, and DTPA are described in this study. The poly(HPMA)-SPD-DTPA (DTPA: diethylenetriaminepentaacetic acid), poly(HPMA)-DTPA, and DTPA conjugates were radiolabeled with the radionuclide 99mTc and tested for uptake by cultured H22 cells. The cellular accumulation of poly(HPMA)-SPD-DTPA-99mTc complex was found to be time-dependent. The poly(HPMA)-SPD-DTPA-99mTc tracer exhibited rapid uptake kinetics in cell culture with a t 1/2 of ∼5 min. The uptake of poly(HPMA)-SPD-DTPA- 99mTc was significantly higher than that of poly(HPMA)-DTPA- 99mTc, indicating that the uptake of the poly(HPMA)-SPD-DTPA- 99mT was active binding. The uptake of poly(HPMA)-DTPA- 99mTc was significantly higher than that of DTPA-99mTc, suggesting that the uptake of the poly(HPMA)-DTPA-99mT was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(HPMA)-SPD-DTPA-99mTc (4.98 ± 0.48%ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-99mTc (2.69 ± 0.15% ID/g) and DTPA-99mTc (0.83 ± 0.03%ID/g). Moreover, higher T/B for poly(HPMA)-SPD-DTPA-99mTc indicated reduced extravazation of the targeted polymeric conjugates in normal tissues. Specific molecular targeting and nonspecific vascular permeability are both significant in the relative tumor localization of poly(HPMA)-SPD-DTPA-99mTc. Extravascular leak in nonspecific organs appears to be a major factor in reducing the T/B for the sulfapyridine molecules. Thus, the poly(HPMA)-SPD-DTPA is expected to be used as the potential macromolecular targeting carrier for hepatoma carcinoma in mice. © 2013 Copyright Taylor & Francis Group, LLC.

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