99mTc-HYNIC-(Ser)3-LTVPWY peptide bearing tricine as co-ligand for targeting and imaging of HER2 overexpression tumor

2018 ◽  
Vol 106 (7) ◽  
pp. 601-609 ◽  
Author(s):  
Nazan Aligholikhamseh ◽  
Sajjad Ahmadpour ◽  
Fatemeh Khodadust ◽  
Seyed Mohammad Abedi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Nude Mice ◽  
Tumor Targeting ◽  
Binding Capacity ◽  
Specific Binding ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Epidermal Growth

Abstract Human epidermal growth factor receptor 2 (HER2) is overexpressed in several cancers. Today’s tumor targeting is receiving more attention due to its specificity to target receptor-dependent cancers. The aim of this study was to evaluate the 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide for tumor targeting and imaging with overexpression of HER2. HYNIC-(Ser)3-LTVPWY peptide was labeled with 99mTc using tricine as a co-ligand at room temperature. Specific binding of this radiolabeled peptide was assessed on four cancer cell lines with different levels of HER2 receptor expression. Also the affinity of 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide to the HER2 receptor was evaluated in the SKOV-3 cell line. Biodistribution study of this radiolabeled peptide was performed in SKOV-3 tumor bearing nude mice. The HYNIC conjugated peptide was simply labeled with 99mTc radionuclide with high labeling efficiency about 98±1% showing favorable stability in normal saline and human serum. In the presence of unlabeled peptide as competitor, the HER2 binding capacity of the radiolabeled peptide reduced (approximately five-fold). The KD and Bmax values were found 2.6±0.5 nM and (2.6±0.1)×106, respectively. The tumor/muscle ratios for this radiotracer were determined 1.17±0.77, 1.15±0.32 and 2.65±0.32 at 1, 2 and 4 h after injection, respectively. Presaturation of HER2 receptors in SKOV-3 xenografted nude mice showed a reduction in the tumor/muscle ratio confirming in vivo specificity of the peptide. According to SPECT imaging, the tumor was visualized in mouse after 4 h postinjection of radiolabeled peptide. 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide exhibited overexpressed HER2 tumor targeting.

Boosting epidermal growth factor receptor expression by gene gun transfection stimulates epidermal growth in vivo

2000 ◽  
Vol 8 (2) ◽  
pp. 117-127 ◽  
Author(s):  
Lillian B Nanney ◽  
Stephen Paulsen ◽  
Mari K Davidson ◽  
Nancy L Cardwell ◽  
Jeffrey S Whitsitt ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Gene Gun ◽  
Epidermal Growth

scholarly journals Imaging Epidermal Growth Factor Receptor Expression In vivo: Pharmacokinetic and Biodistribution Characterization of a Bioconjugated Quantum Dot Nanoprobe

2008 ◽  
Vol 14 (3) ◽  
pp. 731-741 ◽  
Author(s):  
Parmeswaran Diagaradjane ◽  
Jacobo M. Orenstein-Cardona ◽  
Norman E. Colón-Casasnovas ◽  
Amit Deorukhkar ◽  
Shujun Shentu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Quantum Dot ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Epidermal Growth

scholarly journals Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
David S. Y. Chan ◽  
Fiona Campbell ◽  
Paul Edwards ◽  
Bharat Jasani ◽  
Geraint T. Williams ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
High Specificity ◽  
Endoscopic Biopsy ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Predictive Values

Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC, P=0.003). The sensitivity, specificity, positive and negative predictive values of HER2 status at endoscopic biopsy were 56%, 93%, 63%, 91% respectively (weighted Kappa=0.504, P<0.0001). Five-year survival in OC HER2 positive negative was 100% and 36% (P=0.167) compared with 14% and 44% (P=0.0726) in JC and 50% and 46% (P=0.942) in GC respectively. Conclusions. Endoscopic biopsy had a high specificity and negative predictive value in determining HER2 status. Patients with JC had a significantly higher rate of HER2 overexpression and this was associated with a nonsignificant poorer survival trend. A larger study is needed to confirm these findings because of the implications for neoadjuvant and adjuvant chemotherapy regimens.

Histological and Immunohistochemical Identification of Atypical Ductal Mammary Hyperplasia as a Preneoplastic Marker in Dogs

2011 ◽  
Vol 49 (2) ◽  
pp. 322-329 ◽  
Author(s):  
E. Ferreira ◽  
H. Gobbi ◽  
B. S. Saraiva ◽  
G. D. Cassali
Keyword(s):  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Mammary Tissue ◽  
Her2 Overexpression ◽  
Ki 67 ◽  
Molecular Alterations ◽  
Ductal Hyperplasia ◽  
Epidermal Growth ◽  
Malignant Neoplasia ◽  
Immunohistochemical Identification

This study describes and evaluates the morphological and molecular relationship between canine mammary ductal hyperplasias with atypia and canine mammary neoplasias. Ductal hyperplasia was identified in association with malignant neoplasia in 56 of the 115 cases (48,8%), and although ductal hyperplasia without atypia was the type most frequently noted in the cases, most examples of hyperplasia with atypia were associated with mammary tumors. Estrogen receptor, E-cadherin, and cytokeratins 1, 5, 10 and 14 (CK34bE12) expression was quite lower than in normal mammary tissue, and HER2 overexpression was absent in all proliferative cells of ductal hyperplasia. The Ki-67 expression, epidermal growth factor receptor and progesterone receptor expression appeared higher in those hyperplastic lesions analyzed than in normal mammary glands. These findings suggest that canine mammary atypical hyperplasia may play an important role in the process of malignant neoplastic transformation, with molecular alterations that are similar to precursor lesions reported in humans.

scholarly journals The Effect of Estradiol on in Vivo Tumorigenesis Is Modulated by the Human Epidermal Growth Factor Receptor 2/Phosphatidylinositol 3-Kinase/Akt1 Pathway

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1171-1180 ◽  
Author(s):  
Kevin Lehnes ◽  
Abigail D. Winder ◽  
Camille Alfonso ◽  
Natasha Kasid ◽  
Michael Simoneaux ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Volume ◽  
Growth Factor Receptor ◽  
Fold Increase ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Progesterone Receptor Expression ◽  
Epidermal Growth ◽  
Mcf 7

To determine whether the epidermal growth factor receptor 2 (ErbB2) and Akt1 can alter the in vivo growth of MCF-7 cells, parental cells or cells stably transfected with constitutively active Akt1 (myr-Akt1) or dominant-negative Akt1 mutants (K179M-Akt1 and R25C-Akt1) were implanted into athymic nude mice. Tumor growth was monitored in the presence or absence of the antiestrogen tamoxifen and the selective ErbB2 inhibitor, AG825. MCF-7 [parental or empty vector transfected, cytomegalovirus (CMV)] and myr-Akt1 cells formed tumors upon estradiol supplementation after 20–30 d (59-, 29-, and 17-fold increase in tumor volume, respectively). Tamoxifen and AG825 blocked the estradiol effect by 93 and 96% in MCF-7 xenografts, 88 and 81% in CMV xenografts, and 91% in myr-Akt1 xenografts. Furthermore, AG825 suppressed the growth of established tumors in CMV and myr-Akt1 inoculated animals by 68 and 75%, respectively, as compared with continued estrogen supplementation, suggesting a role for ErbB2. When K179M-Akt1 or R25C-Akt1 cells were injected into ovariectomized animals, tumor growth was reduced upon estradiol treatment by 95% and 98%, respectively, supporting a role for Akt1. In contrast to ovariectomized animals, in intact animals, myr-Akt1 cells could establish tumors without estradiol priming after 40–50 d (20-fold increase in tumor volume). Loss of Akt1 phosphorylation was associated with tumor growth inhibition. Immunohistochemical assays showed that in tumors from parental and CMV xenografts, estradiol decreased estrogen receptor-α expression and induced progesterone receptor expression and Akt phosphorylation, effects that were inhibited by tamoxifen, AG825, and R25C-Akt1 by 89, 82, and 77% for progesterone receptor expression and 48, 66, and 73% for pAkt expression, respectively. Cumulatively, our results suggest that Akt1 and ErbB2 are involved in in vivo tumorigenesis and modulation of estrogen receptor-α expression and activity.

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