Comparison of Two Site-Specifically ¹⁸F-Labeled Affibodies for PET Imaging of EGFR Positive Tumors

Su, Xinhui,Cheng, Kai,Jeon, Jongho,Shen, Bin,Venturin, Gianina Teribele,Hu, Xiang,Rao, Jianghong,Chin, Frederick T.,Wu, Hua,Cheng, Zhen American Chemical Society 2014 MOLECULAR PHARMACEUTICS Vol.11 No.11

<P>The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules <SUP>64</SUP>Cu-DOTA-Z<SUB>EGFR:1907</SUB> and <SUP>18</SUP>F-FBEM-Z<SUB>EGFR:1907</SUB> can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with <SUP>64</SUP>Cu, <SUP>18</SUP>F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of <SUP>18</SUP>F-FBEM-Z<SUB>EGFR:1907</SUB> requires a long synthesis time. The aim of the present study is to develop a new generation of <SUP>18</SUP>F labeled affibody probes (Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> and <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB>) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating Z<SUB>EGFR:1907</SUB> with NOTA and radiolabeling with Al<SUP>18</SUP>F to produce Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB>. In a second approach the prosthetic group <SUP>18</SUP>F-labeled-2-cyanobenzothiazole (<SUP>18</SUP>F-CBT) was conjugated to Cys-Z<SUB>EGFR:1907</SUB> to produce <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB>. Binding affinity and specificity of Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> and <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB> to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> or <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB> with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> and <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB> were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB> showed instability <I>in vivo</I>, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> demonstrated high <I>in vitro</I> and <I>in vivo</I> stability, high tumor uptake, and relative low uptake in most of the normal organs except the liver and kidneys at 3 h after injection. The specificity of both probes for A431 tumors was confirmed by their lower uptake on coinjection of unlabeled affibody. PET studies showed that Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> and <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB> could clearly identify EGFR positive tumors with good contrast. Two strategies for <SUP>18</SUP>F-labeling of affibody molecules were successfully developed as two model platforms using NOTA or CBT coupling to affibody molecules that contain an N-terminal cysteine. Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> and <SUP>18</SUP>F-CBT-Z<SUB>EGFR:1907</SUB> can be reliably obtained in a relatively short time. Biodistribution and PET studies demonstrated that Al<SUP>18</SUP>F-NOTA-Z<SUB>EGFR:1907</SUB> is a promising PET probe for imaging EGFR expression in living mice.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2014/mpohbp.2014.11.issue-11/mp5003043/production/images/medium/mp-2014-003043_0008.gif'></P>

Application of modified graphite felt as electrode material: a review

Yang Su,Na Chen,Hai‑lin Ren,Cheng‑wei Li,Li‑li Guo,Zhen Li,Xiao‑min Wang 한국탄소학회 2023 Carbon Letters Vol.33 No.1

Graphite felt is a felt-like porous material made of high-temperature carbonized polymers. It is widely used in electrode materials because of its good temperature resistance, corrosion resistance, large surface area and excellent electrical conductivity. In this paper, the surface functional group modification is of graphite felt electrodes (mainly nitrogen doping modification, nitrogen–sulfur or nitrogen–boron co-doping modification) and surface catalytic modification (metal/ion surface modification and metal oxide surface modification as Main). There are two main methods and research progresses to improve the performance of graphite felt electrodes, and the comprehensive performance of surface functional group-modified graphite felt electrodes and surface catalytically modified graphite felt electrodes are compared respectively. The results show that both surface functional group modification and surface catalytic modification can improve the comprehensive performance of graphite felt electrodes. In this paper, the future development direction of graphite felt activation modification is also prospected.

Identification of ssDNA Aptamers Specific for Anti-neuroexcitation Peptide III and Molecular Modeling Studies: Insights into Structural Interactions

Zhu, Jon,Wang, Jian,Su, Zhen-Cheng,Li, Qin,Cheng, Mao-Sheng,Zhang, Jing-Hai 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9

Twelve ssDNA aptamers specific for a novel recombinant anti-neuroexcitation peptide (ANEPIII) were identified using the SELEX method from a 79-nucleotide ssDNA pool to purify ANEPIII in a more efficient way. To further understand the binding modes between ssDNA and ANEPIII, fully flexible dinucleotides were docked onto the homology-modeled ANEPIII structure. AutoDocking identified favorable binding sites on ANEPIII for nucleotides, which was valuable for designing more potent ligands.

Distinctive Endophytic Fungal Assemblage in Stems of Wild Rice (Oryza granulata) in China with Special Reference to Two Species of Muscodor (Xylariaceae)

Zhi-lin Yuan,Zhen-zhu Su,Li-juan Mao,Yang-qing Peng,Guan-mei Yang,Fu-cheng Lin,Chu-long Zhang 한국미생물학회 2011 The journal of microbiology Vol.49 No.1

Ecological niches in the rhizosphere and phyllosphere of grasses capable of sustaining endophytes have been extensively studied. In contrast, little information regarding the identity and functions of endophytic fungi in stems is available. In this study, we investigated the taxonomic affinities, diversity, and host specificities of culturable endophytes in stems of wild rice (Oryza granulata) in China. Seventy-four isolates were recovered. Low recovery rate (11.7%) indicated that there were relatively few sites for fungal infection. Identification using morphology, morphospecies sorting, and molecular techniques resulted in classification into 50 taxa, 36 of which were recovered only once. Nucleotide sequence similarity analysis indicated that 30% of the total taxa recovered were highly divergent from known species and thus may represent lineages new to science. Most of the taxa were classified as members of the classes Sordariomycetes or Dothideomycetes (mainly in Pleosporales). The presence of Arthrinium and Magnaporthaceae species, most often associated with poaceous plants, suggested a degree of host specificity. A polyphasic approach was employed to identify two Muscodor taxa based on (i) ITS and RPB2 phylogenies, (ii) volatile compounds produced, and (iii)an in vitro bioassay of antifungal activity. This to our knowledge is only the second report regarding the isolation of Muscodor spp. in China. Therefore, we hypothesize that wild plants represent a huge reservoir of unknown fungi. The prevalence, novelty, and species-specificity of unique isolates necessitate a reevaluation of their contribution to ecosystem function and fungal biodiversity.

Identification of ssDNA Aptamers Specific for Anti-neuroexcitation Peptide III and Molecular Modeling Studies: Insights into Structural Interactions

Jun Zhu,Jian Wang,Zhen-Cheng Su,Qin Li,Mao-Sheng Cheng,Jing-Hai Zhang 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9

Twelve ssDNA aptamers specific for a novel recombinant anti-neuroexcitation peptide (ANEPIII) were identified using the SELEX method from a 79-nucleotide ssDNA pool to purify ANEPIII in a more efficient way. To further understand the binding modes between ssDNA and ANEPIII, fully flexible dinucleotides were docked onto the homology-modeled ANEPIII structure. AutoDocking identified favorable binding sites on ANEPIII for nucleotides, which was valuable for designing more potent ligands.

Clinical Application of Recombinant Human Endostatin in Postoperative Early Complementary Therapy on Patients with Non-small Cell Lung Cancer in Chinese Mainland

Zhu, Qiang,Zang, Qi,Jiang, Zhong-Min,Wang, Wei,Cao, Ming,Su, Gong-Zhang,Zhen, Tian-Chang,Zhang, Xiao-Tian,Sun, Ning-Bo,Zhao, Cheng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Objective: To explore the clinical application of recombinant human endostatin (Endostar) in the treatment of patients with non-small cell lung cancer (NSCLC) in Chinese mainland. Materials and Methods: A total of 75 patients diagnosed as NSCLC were randomly divided into control group (37 cases) and treatment group (38 cases). Control group was treated with postoperative complementary chemotherapy containing two-agent platinum protocol on postoperative d21, 3 weeks as a cycle, for totally 4~6 cycles. On this basis, treatment group was added with Endostar $7.5mg/m^2$ on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally 4 cycles. The interval between every two cycles was 7 d. The 5-year progression-free survival (PFS), 5-year survival time and complications in both groups were observed. Results: Compared with control group, the average PFS increased evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and there was significant difference (P<0.05). And the median PFS was 42.5 months in treatment group, obviously longer than that in control group (33.7 months) by 8.8 months (P<0.05). Additionally, the 5-year overall survival rate (OS), average survival time and median survival time (MST) were 47.4%, 50.1 months and 59.3 months in treatment group, significantly higher than the 29.7%, 42.1 months and 43.5 months in control group (P<0.05). Only 1 patient showed poor healing of surgical wound in treatment group, but no surgery-associated complication was found in control group. Moreover, the postoperative complementary therapy-connected complication rates were 63.2% (24/38) and 59.5% (22/37) in treatment group and control group respectively, but there was no significant difference (P>0.05). Conclusions: The application of Endostar combined with sensitive platinum-contained chemotherapeutic agents in the postoperative complementary chemotherapy can be widely used in clinic because it can significantly prolong the long-term survival time of patients with NSCLC.

Distribution and analysis of SSR in mung bean (Vigna radiata L.) genome based on an SSR-enriched library

Wang, Li Xia,Elbaidouri, Moaine,Abernathy, Brian,Chen, Hong Lin,Wang, Su Hua,Lee, Suk Ha,Jackson, Scott A.,Cheng, Xu Zhen Springer-Verlag 2015 Molecular breeding Vol.35 No.1