Radiolabeled NGR phage display peptide sequence for tumor targeting

Faintuch, Bluma Linkowski; Oliveira, Érica Aparecida de; Targino, Roselaine Campos; Moro, Ana Maria

doi:10.1016/j.apradiso.2013.12.035

Cited by 21 publications

(18 citation statements)

References 20 publications

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“…Furthermore, the molecule is upregulated on endothelial cells in tumors and tissues that undergo angiogenesis and is essential for capillary tube formation [12] , [34] . CD13 is often used for tumor imaging [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] . Some NGR peptides bind in particular to a CD13 isoform preferentially present in tumor vascular cells as shown by binding assays using radiolabeled NGR peptide-linked tumor necrosis factor (NGR-hTNF) [11] .…”

Section: Discussionmentioning

confidence: 99%

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Keßler

Baumeier

Brand

et al. 2018

Translational Oncology

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Aminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS who were treated by wide resection and uniform chemo-radio-chemotherapy. Using a semiquantitative score with four intensity levels, CD13 was expressed by tumor vasculature, or tumor cells, or both (composite value, intensity scores 1-3) in 93.9% of the STS. In 49.5% tumor cells, in 48.5% vascular/perivascular cells, and in 58.8%, composite value showed strong intensity score 3 staining. Leiomyosarcoma and synovial sarcoma showed low expression; fibrosarcoma and undifferentiated pleomorphic sarcoma showed high expression. We found a significant prognostic impact of CD13, as high expression in tumor cells or vascular/perivascular cells correlated with better relapse-free survival and overall survival. CD13 retained prognostic significance in multivariable analyses. Systemic tTF-NGR resulted in significant growth reduction of CD13-positive human HT1080 sarcoma cell line xenografts. Our results recommend further investigation of tTF-NGR in STS patients. CD13 might be a suitable predictive biomarker for patient selection.

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Section: Discussionmentioning

confidence: 99%

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Keßler

Baumeier

Brand

et al. 2018

Translational Oncology

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“…The high‐affinity ligands (radiolabeled peptides) specific toward tumor vasculature targets are capable of precise detection and imaging of cancerous lesions . One such key molecular target, aminopeptidase N (APN/CD13) receptor, crucially involved in tumor progression and metastasis is being investigated with NGR peptide‐based PET/SPECT molecular imaging probes . 68 Ga‐labeled NGR peptides conjugated with different chelators, DOTA, NOTA, HBED‐CC have been individually reported in different studies and in different animal models .…”

Section: Discussionmentioning

confidence: 99%

Comparative evaluation of ⁶⁸Ga‐labeled NODAGA, DOTAGA, and HBED‐CC‐conjugated cNGR peptide chelates as tumor‐targeted molecular imaging probes

et al. 2017

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The biological behavior of Ga-based radiopharmaceuticals can be significantly affected by the chelators' attributes (size, charge, lipophilicity). Thus, this study aimed at examining the influence of three different chelators, DOTAGA, NODAGA, and HBED-CC on the distribution pattern of Ga-labeled NGR peptides targeting CD13 receptors. Ga-DOTAGA-c(NGR), Ga-NODAGA-c(NGR), and Ga-HBED-CC-c(NGR) were observed to be hydrophilic with respective log p values being -3.5 ± 0.2, -3.3 ± 0.08, and -2.8 ± 0.14. The three radiotracers exhibited nearly similar uptake in human fibrosarcoma HT-1080 tumor cells with 86%, 63%, and 33% reduction during blocking studies with unlabeled cNGR peptide for Ga-DOTAGA-c(NGR), Ga-NODAGA-c(NGR), and Ga-HBED-CC-c(NGR), respectively, indicating higher receptor specificity of the first two radiotracers. The neutral radiotracer Ga-NODAGA-c(NGR) demonstrated better target-to-non-target ratios during in vivo studies compared to its negatively charged counterparts, Ga-DOTAGA-c(NGR) and Ga-HBED-CC-c(NGR). The three radiotracers had similar HT-1080 tumor uptake and being hydrophilic exhibited renal excretion with minimal uptake in non-target organs. Significant reduction (p< .005) in HT-1080 tumor uptake of the radiotracers was observed during blocking studies. It may be inferred from these studies that the three radiotracers are promising probes for in vivo imaging of CD13 receptor expressing cancer sites; however, Ga-NODAGA-c(NGR) is a better candidate.

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“…Nowadays, the PET and SPECT imaging of tumor neoangiogenesis with isotope labeled tracers targeting Aminopeptidase N (APN/CD13) and integrin receptors is an intensively investigated field in oncology (Faintuch et al, 2014;Ma et al, 2013Ma et al, , 2014. In this paper, we focused on the PET imaging of APN/CD13 receptor expression in experimental rat tumor models using a new 68 Ga labeled radiotracer NOTA-c(NGR).…”

Section: Discussionmentioning

confidence: 99%

In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer 68Ga-NOTA-c(NGR)

Máté

Kertész

Enyedi

et al. 2015

European Journal of Pharmaceutical Sciences

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Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine-glycinearginine (NGR) peptides specifically bind to APN/CD13. The aim of the study was to synthesize and investigate the APN/CD13 specificity of a novel 68

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Radiolabeled NGR phage display peptide sequence for tumor targeting

Cited by 21 publications

References 20 publications

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Comparative evaluation of ⁶⁸Ga‐labeled NODAGA, DOTAGA, and HBED‐CC‐conjugated cNGR peptide chelates as tumor‐targeted molecular imaging probes

In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer 68Ga-NOTA-c(NGR)

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Radiolabeled NGR phage display peptide sequence for tumor targeting

Cited by 21 publications

References 20 publications

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Comparative evaluation of 68Ga‐labeled NODAGA, DOTAGA, and HBED‐CC‐conjugated cNGR peptide chelates as tumor‐targeted molecular imaging probes

In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer 68Ga-NOTA-c(NGR)

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Comparative evaluation of ⁶⁸Ga‐labeled NODAGA, DOTAGA, and HBED‐CC‐conjugated cNGR peptide chelates as tumor‐targeted molecular imaging probes