Labeling and distribution of linear peptides identified using in vivo phage display selection for tumors

Kennel, Stephen J.; Mirzadeh, Saed; Hurst, Gregory B.; Foote, Linda J.; Lankford, Trish K.; Glowienka, Kirsten A; Chappell, Lara L.; Kelso, Julie R; Davern, Sandra; Safavy, Ahmad; Brechbiel, Martin W.

doi:10.1016/s0969-8051(00)00149-9

Cited by 25 publications

(10 citation statements)

References 33 publications

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“…For example, coupling of chelators has been shown to result in appreciable loss of target-binding capacity of linear phage display selected peptides. 45 In our case, all anti-EGFR Affibody molecules preserved the capacity to bind to EGFR-expressing cell lines after chelate coupling and radiolabeling. Most likely, the robust scaffold of Affibody molecules prevented any undesirable conformational change.…”

Section: Discussionmentioning

confidence: 57%

Directed Evolution to Low Nanomolar Affinity of a Tumor-Targeting Epidermal Growth Factor Receptor-Binding Affibody Molecule

Friedman

Orlova

Johansson

et al. 2008

Journal of Molecular Biology

144

157

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Section: Discussionmentioning

confidence: 57%

Directed Evolution to Low Nanomolar Affinity of a Tumor-Targeting Epidermal Growth Factor Receptor-Binding Affibody Molecule

Friedman

Orlova

Johansson

et al. 2008

Journal of Molecular Biology

144

157

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“…In fact, this ErbB-2 tumor -targeting peptide is one of the first phage displayselected peptides other than the vasculature-targeting peptides (42) that have been used successfully in tumor imaging in vivo. In 2000, a report concluded that peptides isolated from phage display do not bind with high retention to tumors in vivo (43). Since then, a few studies have reported sequences from phage libraries that target neuroblastomas and prostate tumors in vivo; however, in these cases, the target antigens remain unknown (44,45).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

Kumar

Quinn

Deutscher

2007

Clinical Cancer Research

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Purpose: The cellular targeting and tumor imaging properties of a novel ErbB-2-avid peptide, discovered from bacteriophage display, were evaluated in human breast carcinoma cells and in breast carcinoma^xenografted mice. Experimental Design: The affinity of the ErbB-2 targeting peptide KCCYSL and its alanine substituted counterparts for the extracellular domain (ECD) of purified recombinant ErbB-2 (ErbB-2-ECD) was assessed by fluorescence titration. Binding of the KCCYSL peptide to breast and prostate carcinoma cells was analyzed by confocal microscopy. A DOTA(GSG)-KCCYSL peptide conjugate was radiolabeled with 111 In, and stability, target binding, and internalization were analyzed in vitro. In vivo biodistribution and single-photon emission computed tomography imaging studies were done with the radiolabeled peptide in MDA-MB-435 human breast tumorb earing severe combined immunodeficient mice. Results: KCCYSL peptide exhibited high affinity (295 F 56 nmol/L) to ErbB-2-ECD. Substitution of alanine for lysine, tryptophan, and cysteine reduced the peptide affinity f 1-to 2.4-fold, whereas replacing leucine completely abolished binding. Both biotin- KCCYSL and 111 In-DOTA(GSG)-KCCYSL were capable of binding ErbB-2^expressing human breast carcinoma cells in vitro. Approximately 11% of the total bound radioactivity was internalized in the carcinoma cells. Competitive binding studies indicated that the radiolabeled peptide exhibited an IC 50 value of 42.5 F 2.76 nmol/L for the breast carcinoma cells.

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“…In some cases, the conjugation of a chelator induced a strong change of the secondary structure and resulted in a conjugate with improved the characteristics (higher binding affinity and better stability to peptidases) in comparison with its non-conjugated counterpart [81]. However, the attachment of prosthetic groups, linkers and chelators can have an adverse influence on the binding of short peptides to molecular targets [83].…”

Section: Peptides As Imaging Agentsmentioning

confidence: 99%

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Tolmachev

Orlova

2010

CMC

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Progress in genomics and proteomics provides clinical oncology with new anti-cancer drugs, which target selectively aberrantly expressed membrane proteins and associated signalling pathways in malignant cells. Molecular targeting also enables specific delivery of cytotoxic substances to tumours sparing healthy tissues. Improved selectivity of the treatment reduces side effects and widens the therapeutic window. However, only a part of the patients might benefit from such treatment due to inter- and intrapatient heterogeneity of therapeutic target expression. This makes it necessary to identify patients, who may benefit from targeting therapy. Radiolabelled peptides can provide selective and sensitive detection of molecular therapeutic targets in both primary tumours and metastases in a single non-invasive procedure, making personalised treatment possible. The choice of detection method (single photon emission tomography or positron emission tomography), radionuclide for labelling and labeling chemistry can appreciably influence the imaging property of a tracer. The labelling method might affect the binding affinity, the cellular processing and retention of a radionuclide, the biodistribution of a targeting peptide, and excretion pathways of a non-bound tracer and radiocatabolites. This influences the sensitivity and specificity of the imaging. This influence is exemplified by three classes of tumour-targeting peptides: somatostatin analogues, bombesin analogues and Affibody molecules. The review suggests approaches for selection of an optimal labelling chemistry.

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Labeling and distribution of linear peptides identified using in vivo phage display selection for tumors

Cited by 25 publications

References 33 publications

Directed Evolution to Low Nanomolar Affinity of a Tumor-Targeting Epidermal Growth Factor Receptor-Binding Affibody Molecule

Directed Evolution to Low Nanomolar Affinity of a Tumor-Targeting Epidermal Growth Factor Receptor-Binding Affibody Molecule

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

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