Figure 1 - uploaded by Ann-Marie Broome
Content may be subject to copyright.
EGFR peptide ligands (EGF pep ) have been used in this 

EGFR peptide ligands (EGF pep ) have been used in this 

Source publication
Article
Full-text available
We have developed a near-infrared (NIR) probe that targets cells overexpressing the EGF receptor (EGFR) for imaging glioblastoma brain tumors in live subjects. A peptide specific for the EGFR was modified with various lengths of monodiscrete polyethylene glycol (PEG) units and a NIR Cy5.5 fluorescence dye. The lead compound, compound 2, with one un...

Context in source publication

Context 1
... in the right striatum at a depth of 3 mm from dura with a 10- m L syringe (23-G needle). The needle was slowly withdrawn and the incision was closed with 2 to 3 sutures. Brain tumors grew for 10 to 12 days as per IACUC protocols at which point in vivo imaging studies were conducted. As control for the effects of surgical intervention, animals were also subjected to the implantation procedure but received 2 m L PBS (sham animals). Animals were fed exclusively on a special rodent diet (Harlan Laboratories, Inc.; Tekland 2018S) to reduce autofluorescence. Mice bearing brain tumors derived from Gli36 D 5 or U87-MG cells were administered with compounds at 1 nmol/g via tail vein injection. In vivo competition assays were done with mixture of compound 2 and 10-fold concentration of nonlabeled probe 5. Before injection, mice were anesthetized with isoflurane and subjected to tomographic and spectral fluorescence imaging. One hour after injection, animals were re-imaged. Brains were then extracted and imaged. The excised brains were embedded in Tissue-Tek optimum cutting temperature for cryosections for immunohistochemistry (IHC). Fluo- rescence-mediated molecular tomography (FMT) images were obtained using FMT2500 (Perkin-Elmer), and 3- dimensional reconstructions of fluorescent signals were acquired using the accompanying software TrueQuant. Quantitative fluorescent signals for Cy5.5 of compound 2 were calibrated as per manufacturer’s instructions using the 680-channel. Region of interest (ROI) assigned on the basis of the precise placement of cells during implantation at 3 to 4 mm into the brain. ROI was corroborated with fluorescent signals from ex vivo imaging. Fluorescent multispectral images were obtained using the Maestro In-Vivo Imaging System (CRi, Inc.). The yellow filter set appropriate for Cy5.5 was used for emission and excitation light. The tunable filter was automatically stepped in 10-nm increments whereas the camera captured images at a constant exposure of 200 ms. Fluorescence images were acquired before treatment, immediately after and 1.5 hours after treatment. To compare signal intensities, ROIs were selected over the tumor or nontumor areas, and the change in fluorescence signal over baseline was determined. The spectral fluorescent images consisting of autofluorescence spectra and imaging probe were captured and unmixed on the basis of their spectral patterns. The total signal in the ROI defined in photons measured at the surface of the animal was divided by the area (in pixels). Spectral libraries were generated by assigning spectral peaks to background and fluorescence probe on tissue. The spectral libraries were manually computed using the Maestro software, with each tissue used as its own background control. Sections (2 mm) of whole mouse brains implanted with Gli36 D 5 cells were fixed with 4% paraformaldehyde, cryosectioned onto microscope slides, rinsed with PBS, and blocked with 1% host serum for 30 minutes at room temperature. Sections were incubated with primary antibody at room temperature for 2 hours. Antibodies used were mouse anti-human wild-type EGFR (1:100 dilution; clone DAK-H1-WT, Dako cat. no. M7289). The coverslips were then rinsed with PBS and counterstained with DAPI for 10 minutes at room temperature to visualize the nuclei. After a final rinse with PBS, the slides were mounted with coverslips using Fluor-Mount aqueous media, sealed with nail polish, and observed using epifluorescence microscopy. Cell extracts (50 m g) were fractionated using SDS-PAGE and transferred onto a nitrocellulose membrane. Immu- noblotting was done using a 1:500 dilution of an antibody against wild-type EGFR (DAKO, DAK-H1-WT) or a 1:500 dilution of a specific antibody against mutant EGFRvIII (Bioss Inc., cat# bs-2558R). Horseradish peroxidase–con- jugated secondary antibodies against mouse IgG (Chemi- con) or rabbit IgG (Amersham) were used. Bands were detected using an enhanced chemiluminescence detection system (Pierce). Analyses of data were achieved with GraphPad Prism version 4.00, GraphPad Software. Binding affinity was determined with nonlinear regression analysis with one site binding hyperbola with an equation: Y 1⁄4 B max  X ( K d þ X ), where B max is the maximal binding site and the K d is the concentration required to reach half-maximal binding. ANOVA analysis at 95% confidence interval (CI) was used to compare treatments ( à , P > 0.05; Ãà , P > 0.01; confidence interval, ÃÃà , P > 0.001). To compare live animal FMT, nonparametric one-way ANOVA analyses (Krus- kal–Wallis tests) and the median differences were considered significant with P 1⁄4 0.0220. The goal of these studies was to develop a peptide- based NIRF probe that would cross the BBTB and selectively bind to brain tumor cells overexpressing EGFR. For these studies, we used a peptide discovered through phage display screening against purified human EGFR (9). The peptide was modified to include linkers and a NIRF dye (Fig. 1). To determine the optimal space between the NIRF dye and the peptide, we designed and synthesized a series of peptides to include increasing numbers of discrete ethylene glycol units to serve as linkers between a Cy5.5 and the N-terminal end of the peptide. Cy5.5 and EGFpep were either directly linked or linked via 1, 2, or 3 units of discrete ethylene glycol (AEEA) moieties (Table 1). To determine which of the compounds optimally interacts with cells expressing EGFR, the apparent binding for each bioconjugate was fluorometrically determined from a saturation binding assay (16) in vitro using a human GBM cell line overexpressing EGFR and Gli36 D 5 (Table 1). Compounds 1, 2, 3, and 4 all bound to the cells with affinities in the micromolar range. Compound 2, which had one linker, had the highest apparent affinity with a K d at least 2-fold better than compound 1, which had no ethylene linker, 8.9 to 18.5 m mol/L respectively. Compounds 3 and 4 have weaker affinities with K d of 64.4 and 123.0 m mol/L, respectively. We next used immunofluorescence microscopy to determine the fate of the peptide complexes once they bound to glioblastoma cells expressing EGFR. As pre- dicted from the affinity measurements compound 2, which had the highest affinity, also showed the greatest accumulation of fluorescence after incubation with Gli36 D 5 cells (Fig. 2A). Neither compound 1 (no linker) nor either of the molecules with greater linker numbers (compounds 3 and 4) was taken up by the cells to the same extent as compound 2. Interestingly, the peptide with the longest linker and the worst binding affinity, compound 4, was taken up by cells better than compound 3 (Fig. 2B). When tested against U87-MG cells, which express much lower levels of the EGFR, no cellular uptake for any of the compounds was observed (Fig. 2C). We next tested the ability of these compounds to target EGFR-expressing tumors implanted within the brains of mice. For these studies, mice were orthotopically implanted with Gli36 D 5 cells. Approximately 10 days after implantation, the animals were administered 1 nmol/g via tail vein injection and sacrificed 1 hour later. Brains were harvested and imaged ex vivo for accumulation of the imaging probe. As a control for specificity, we synthesized a Cy5.5-labeled scrambled peptide, compound 6, using the amino acid residues of the parent peptide (compound 5) in random order. Compound 2 targeted the tumor efficiently, accumulat- ing 1.1% of injected dose (Fig. 3A, left graph). In contrast, compound 6 did not target the tumor with delivery of only 0.006% of the injected dose. To further assess specificity, animals that bore Gli36 D 5 brain tumors were administered compound 2 alone or in the presence of a 10-fold excess of unlabeled peptide (compound 5). In animals that received only compound 2, there was significant tumor-associated fluorescence. In contrast, when a 10-fold excess of competitor peptide was coad- ministered with compound 2, there was approximately a 60% decrease in accumulation of the probe, (Fig. 3A, right graph). Imaging and quantification of identical ROIs taken on the contralateral brain showed little uptake of the probe (data not shown). To show that the uptake was associated with human EGFR expression on the Gli36 D 5 cells, the resected brains were fixed and subjected to IHC with monoclonal antibodies specific for human EGFR (Fig. 3B). These results have shown that only cells that expressed human EGFR were associated with Cy5.5 fluorescence. Notably, no Cy5.5 signal was associated with surrounding mouse brain. Our final test for compound 2 was to determine whether it would be useful for noninvasive in vivo detection and discrimination of tumors differentially expressing EGFR. For these studies, mice were orthotopically implanted with either Gli36 D 5 cells, which express high EGFR, or U87-MG cells, which express relatively low EGFR levels (Fig. 4A). Following implantation, the tumors were allowed to grow approximately 10 to 12 days and then mice were administered 1 nmol/g of compound 2 via tail vein injection. One hour after injection, the mice were anesthetized and the intensity of Cy5.5 fluorescence from the tumor was noninvasively quantified using FMT (Fig. 5A). The tumors formed from Gli36 D 5 cells had approximately 4-fold more fluorescence than either tumors formed with U87-MG cells or control sham surgeries (Fig. 5B). For Gli36 D 5 and U87-MG brain tumors, these fluorescence signals corresponded to injected doses of 1.1% and 0.27%, respectively. Statistical analyses showed that the median fluorescence signals between the 2 groups were significantly different (Fig. 5B). To corroborate these data, tumors were excised and subjected to ex vivo FMT and Maestro fluorescence imaging analyses (Fig. 5C and D). These measurements were in good agreement with those measurements made during the live animal imaging. We also examined the expression of EGFRvIII in the cell lines. ...

Citations

... Therefore, for our initial foray into this chemical space, we chose to deploy GE11 to develop a synthetic protocol for peptide conjugation with a polypyridyl-amine chelator. Conflicting results pointing both to specific targeting [23,[25][26][27][28][29][30][31][32][33] and to little or no specific binding in vitro and in vivo have, however, emerged from investigations of GE11 attached to radiolabels [24,[34][35][36]. To what extent these discrepancies might be due to variations in the chelator, radioisotope, linker, and number of GE11 peptides in the different radiopharmaceutical constructs is unclear. ...
Article
Full-text available
The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (58mCo) and the Positron Emission Tomography-isotope cobalt-55 (55Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co2+ and Co3+. With cobalt-57 (57Co) serving as a surrogate radionuclide for 55/58mCo, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [57Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of 57Co from the complex. In conclusion, [57Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR.
... Fluorescence-guided surgery (FGS) is an alternative or adjunct strategy that aims to provide real-time tumor visualization directly from the tissue [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. The approach involves administering a fluorescent contrast agent designed to accumulate in or otherwise target tumors and using a fluorescence imaging system during surgery to visualize the agent distribution. ...
Article
Full-text available
Imaging of tumor-specific fluorescent contrast agents to guide tumor removal has been shown to improve outcomes and is now standard practice for some neurosurgical procedures. However, many agents require administration hours before surgery, a practical challenge, and may exhibit inconsistent concordance with contrast-enhanced MRI (CE-MRI), the current standard for diagnosing and guiding glioma removal. A fluorescent agent that accurately marks tumor shortly after administration and is otherwise similar to CE-MRI would help overcome these shortcomings. Methods: We used whole-body 3-D fluorescence cryo-imaging and co-registered CE-MRI volumes to evaluate several fluorescent contrast agent candidates for diagnostic performance and concordance with CE-MRI. Mice with brain tumors were administered a cocktail of fluorescent agent candidates and a MRI contrast agent, and then imaged with MRI and fluorescence cryo-imaging at several timepoints after administration. The high-resolution 3-D cryo-imaging volumes of the fluorescent agents were used to determine diagnostic performance metrics and correlation with CE-MRI. Results: While all agents showed positive metrics, one agent, tetramethylrhodamine conjugated to a small polyethylene glycol chain (TMR-PEG1k), outperformed the others, exhibiting minimal normal brain signal, high tumor-to-background-ratio, diagnostic accuracy, and cross-correlation to CE-MRI at all post-administration timepoints (10-90 min) and tumor lines examined. Conclusion: These favorable properties establish TMR-PEG1k as a promising candidate for surgical guidance.
... When an extracellular ligand such as EGF binds to EGFR at the cell surface, receptor dimerization occurs, leading to further activation of the kinase domain and downstream signaling pathways [4,5]. Due to the complexity of the structure and function of EGFR, research on the EGFR protein visualization has proved challenging, in particular, fluorescence visualization has become an important research tool [6,7]. Significant progress in EGFR visualization continues to be made, and is generally based on the following strategies: genetically encoded fluorescent biosensors [8], and EGF or cetuximab antibodies conjugated with fluorescent tags to bind to the EGFR extracellular domain [9][10][11][12]. ...
Article
Full-text available
Overexpression of human epidermal growth factor receptor (EGFR) plays an important role in several signaling pathways inside and outside the cell, especially in the processes of cell proliferation, differentiation, and death in various cancers. Due to the complexity of the structure and function of EGFR, research on the fluorescence visualization of EGFR protein visualization has proved challenging. One possible strategy for designing a receptor-targeting fluorescent probe with a switching mechanism is to introduce an environment-sensitive fluorophore into the drug ligand. Based on this strategic molecular design, we introduced two environment-sensitive small molecular fluorophores, dansyl chloride (DNS) and nitrobenzoxadiazole (NBD), to replace the morpholine group of gefitinib, achieving a series of fluorescent molecular probes bearing a switching mechanism. The GN probes exhibited prominent environment sensitivity, suggesting good performance as turn-on EGFR-targeting fluorescent ligands. The representative probe GN3 specifically responded to tumor cells overexpressing EGFR, which was validated with live-cell fluorescence imaging and in vivo xenograft tumor imaging. Ligand-induced EGFR phosphorylation in A431 cells was considerably inhibited by probe GN3, demonstrating that this probe still functions as an EGFR inhibitor. Owing to the turn-on response of GN3 to EGFR in tumor cells, and the competitive replacement behavior to the EGFR inhibitor gefitinib, these probes have the potential to be used for fluorescence imaging of cells overexpressing EGFR.
... The higher the accumulation, the greater the cell death. In the same year [91], the authors optimized various parameters, i.e. the density of the GE11 peptide ligand on the micelle surface, the Pc4 loading and the light dose, in order to enhance the PDT efficiency. They discovered that the micelle formulation should be of 10% mole GE11-modified polymer and 50 μg Pc4 per mg of polymer. ...
Article
Full-text available
Cancer is the second leading cause of death worldwide after cardiovascular disease. Depending on the type and the location of the tumor, several cancer treatments are implemented. Among these, the three most conventional therapies are surgery, radiotherapy and chemotherapy. However, there are other therapeutic approaches such as photodynamic therapy (PDT). PDT relies on the combined action of light, a photoactivable molecule called photosensitizer (PS) and molecular oxygen. Most of the PSs used for clinical applications are not cancer-cell specific. One of the solutions to overcome this problem is the use of nanoparticles (NPs) to induce a passive targeting. It is also possible to graft a vector onto the NPs to specifically target membrane receptors overexpressed in the tumor cells or neovessels surrounding the tumor. In this review, we focus on the NPs loaded with PSs and coupled to peptides for targeted PDT. We described nanosystems that targeted Neuropilin-1 (NRP-1), αvβ3 integrins, nucleolin membrane receptor, epidermal growth factor (EGF) receptor, protein-glutamine-gamma-glutamyltransferase (TGM2), p32, transferrin, PD-1, and mitochondrial membrane. The use of a cell absorbing-peptide is also described.
... Various groups have demonstrated the applicability of the GE11 peptide for the specific targeting toward the EGFR receptor for different purposes [153,154], including drug delivery [155][156][157][158]. Importantly, Ohno et al., (2013) showed that the delivery of micro RNA (miRNA) to EGFR-expressing breast cancer cells can be achieved efficiently by EVs. For this, the donor cells were engineered to express the transmembrane domain of the plateletderived growth factor receptor fused to the GE11 peptide. ...
Article
Full-text available
Peptides are strings of approximately 2–50 amino acids, which have gained huge attention for theranostic applications in cancer research due to their various advantages including better biosafety, customizability, convenient process of synthesis, targeting ability via recognizing biological receptors on cancer cells, and better ability to penetrate cell membranes. The conjugation of peptides to the various nano delivery systems (NDS) has been found to provide an added benefit toward targeted delivery for cancer therapy. Moreover, the simultaneous delivery of peptide-conjugated NDS and nano probes has shown potential for the diagnosis of the malignant progression of cancer. In this review, various barriers hindering the targeting capacity of NDS are addressed, and various approaches for conjugating peptides and NDS have been discussed. Moreover, major peptide-based functionalized NDS targeting cancer-specific receptors have been considered, including the conjugation of peptides with extracellular vesicles, which are biological nanovesicles with promising ability for therapy and the diagnosis of cancer.
... Therefore, we used CRT to develop NIRF probes for visualizing GBM. Cy5is very suitable for intraoperative imaging, and others have developed peptides conjugated with Cy5 to image tumors [32][33][34][35][36].Focusing on the high affinity between CRT and TfR 1, we synthesizedCy5-CRT. When considering a probe for intraoperative fluorescence imaging, the selectivity of tumor delineation is a crucial issue. ...
Article
Full-text available
Objective Optical molecular imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons effectively remove tumor masses. Transferrin receptor 1 (TfR 1) is a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT), was shown to cross the blood brain barrier (BBB) and accumulate at high levels in GBM tissues. In this study, we synthesized a TfR 1-targeted near-infrared fluorescent (NIRF) probe, Cy5-CRT, for identifying the GBM tissue margin in mouse models.Methods We initially confirmed the overexpression of TfR 1 in GBM and the tumor-specific homing ability of Cy5-CRT in subcutaneous and orthotopic GBM mouse models. We then examined the feasibility of Cy5-CRT for identifying the tumor margin in orthotopic GBM xenografts. Finally, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins.ResultsCy5-CRT specifically accumulated in GBM tissues and detected the tumor burden with exceptional contrast in mice with orthotopic GBM, enabling fluorescence-guided GBM resection under NIRF live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium.Conclusions The TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from the surrounding normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM.
... Specific binding to EGFR, including peptide or antibody binding, is one of the current approaches for visualisation of tumour margins [18,19]. The introduction of GE-7 or GE-11 peptide and fluorescent label Dy-633 into the HPMA polymer should enable specific ligand-mediated targeting to EGFR-positive cells overexpressed in HNSCC cells [8]. ...
... This, together with the high hydrophobic character of GE11, led to the suggestion that the peptide has a strong tendency for aggregation preventing the EGFR-targeting ability (Ongarora et al. 2012). Results from a study with a Cy-dye and PEG-based linked GE11 represented a measurable but low affinity (µM range), in glioblastoma cells (Agnes et al. 2012). A recent study with 99m Tc-labeled HYNIC-GE11 revealed an affinity of 73 nM in ovarian tumor cells (Rahmanian et al. 2017). ...
Article
Full-text available
The epidermal growth factor receptor (EGFR) represents an important molecular target for both radiotracer-based diagnostic imaging and radionuclide therapy of various cancer entities. For the delivery of radionuclides to the tumor, peptides hold great potential as a transport vehicle. With respect to EGFR, the peptide YHWYGYTPQNVI (GE11) has been reported to bind the receptor with high specificity and affinity. In the present study, GE11 with β-alanine (β-Ala-GE11) was conjugated to the chelating agent p-SCN-Bn-NOTA and radiolabeled with 64Cu for the first radio pharmacological evaluation as a potential probe for positron emission tomography (PET)-based cancer imaging. For better water solubility, an ethylene glycol-based linker was introduced between the peptide's N terminus and the radionuclide chelator. The stability of the 64Cu-labeled peptide conjugate and its binding to EGFR-expressing tumor cells was investigated in vitro and in vivo, and then compared with the 64Cu-labeled EGFR-targeting antibody conjugate NOTA-cetuximab. The GE11 peptide conjugate [64Cu]Cu-NOTA-linker-β-Ala-GE11 ([64Cu]Cu-1) was stable in a buffer solution for at least 24 h but only 50% of the original compound was detected after 24 h of incubation in human serum. Stability could be improved by amidation of the peptide's C terminus (β-Ala-GE11-NH2 (2)). Binding assays with both conjugates, [64Cu]Cu-1 and [64Cu]Cu-2, using the EGFR-expressing tumor cell lines A431 and FaDu showed no specific binding. A pilot small animal PET investigation in FaDu tumor-bearing mice revealed only low tumor uptake (standard uptake value (SUV) < 0.2) for both conjugates. The best tumor-to-muscle ratio determined was 3.75 for [64Cu]Cu-1, at 1 h post injection. In conclusion, the GE11 conjugates in its present form are not suitable for further biological investigations, since they presumably form aggregates.
... The in vivo imaging necessitates use of a relatively narrow window of light wavelengths for photoexcitation (in the range of 650-1350 nm) to avoid strong scattering or absorption by fat, hemoglobin, or water. Therefore, application of near-infrared fluorophores that utilize the so-called therapeutic window is currently on the rise [33,43,45,46,50,[79][80][81][82][83][84]. Furthermore, two-photon excitation strategy has gained popularity, which takes advantage of the fact that for excitation of certain fluorophores, instead of using one photon with high energy, two photons with half the energy can be applied [85]. ...
... Another important aspect in development of Class 3A probes is that while it is tempting to extrapolate properties of the sensing fragment to the whole probe, conjugating of the label with the inhibitor can result in significant change of characteristics of the latter [79,167,168]. Therefore, it is of utmost importance to establish affinity, kinetics, selectivity and cell membrane-penetrating properties of the probe after it has been fully assembled. ...
Article
Full-text available
Protein kinases catalyze phosphorylation, a small yet crucial modification that affects participation of the substrate proteins in the intracellular signaling pathways. The activity of 538 protein kinases encoded in human genome relies upon spatiotemporally controlled mechanisms, ensuring correct progression of virtually all physiological processes on the cellular level—from cell division to cell death. The aberrant functioning of protein kinases is linked to a wide spectrum of major health issues including cancer, cardiovascular diseases, neurodegenerative diseases, inflammatory diseases, etc. Hence, significant effort of scientific community has been dedicated to the dissection of protein kinase pathways in their natural milieu. The combination of recent advances in the field of light microscopy, the wide variety of genetically encoded or synthetic photoluminescent scaffolds, and the techniques for intracellular delivery of cargoes has enabled design of a plethora of probes that can report activation of target protein kinases in human live cells. The question remains: how much do we bias intracellular signaling of protein kinases by monitoring it? This review seeks answers to this question by analyzing different classes of probes according to their general structure, mechanism of recognition of biological target, and optical properties necessary for the reporting of intracellular events.
... The radiochemical purity was 95% within 4 h incubation time and no significant impurities including 99m TcO 4 − , RHT and 99m Tc-coligand were released. It has been reported previously that GE11 is able to bind EGFR especially those of human hepatoma cell line SMMC-7721 [11], human non-small cell lung carcinoma cell line H1299 [12], human glioblastoma astrocytoma U87-MG [32], non-small cell lung cancer A549 [33], human ovarian adenocarcinoma SKOV3 [14,16] and breast cancer HCC70 cells [34]. In this study the tendency of 99m Tc-tricine-GE11 complex in binding to SKOV3, A549 and MCF-7 cell lines were compared. ...
Article
Full-text available
Background Ovarian cancer is a serious threat for women health and the early diagnosis of this cancer might improves the survival rate of patients. The use of the targeted radiopharmaceuticals could be a non-invasive and logical method for tumor imaging. The aim of this study was to radiolabel GE11 peptide as a new specific probe for imaging of ovarian tumor. MethodsHYNIC-SSS-GE11 peptide was labeled with 99mTc using tricine as a coligand. The 99mTc-tricine-HYNIC-SSS-GE11 peptide was evaluated for specific cellular binding in three cell lines with different levels of EGFR expression. Tumor targeting was assessed in SKOV3 tumor bearing mice. ResultsBy using tricine as a coligand, labeling yield was more than 98% and the stability of the radiolabelled peptide in human serum up to 4 h was 96%. The in vitro cell uptake test showed that this radiolabeled peptide had a good affinity to SKOV3 cells with dissociation constant of 73 nM. The in vivo results showed a tumor/muscle ratio of 3.2 at 4 h following injection of 99mTc-tricine-HYNIC-SSS-GE11 peptide. Conclusions Results of this study showed that 99mTc-tricine-HYNIC-SSS-GE11 peptide could be a promising tool for diagnosis and staging of ovarian cancer. Graphical Abstract99mTc-tricine-HYNIC-SSS-GE11, a novl targeted agent for ovarian tumor imagingOpen image in new window