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

Máté, Gábor; Kertész, István; Enyedi, Kata Nóra; Mező, Gábor; Angyal, János; Vasas, Nikolett; Kis, Anna; Szabó, Éva; Emri, Miklós; Bı́ró, Tamás; Galuska, László; Trencsényi, György

doi:10.1016/j.ejps.2015.01.002

Cited by 46 publications

(74 citation statements)

References 47 publications

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“…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 . Here, we focused to explore the role of chelators, DOTAGA, NODAGA, and HBED‐CC on the pharmacokinetic pattern of 68 Ga‐labeled NGR peptide at one platform.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…There are earlier reports of conjugation of NGR peptides with DOTA and NOTA chelators and radiolabeling with 68 Ga as well as using 64 Cu for PET imaging of CD13 receptor‐positive tumors . Size, coordination, and the basic structure of the chelator have a definite influence on the biological behavior of radiotracers .…”

Section: Introductionmentioning

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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“…CD13 is expressed by many cells of normal tissue, including epithelial cells from small intestine, prostate, bile duct canaliculi and myeloid cells while it is upregulated in angiogenic blood vessels and, in some cases by fibroblasts [20,[22][23][24][25][26][27][28][29]. Several peptides containing the NGR tripeptide motif that specifically recognize the CD13 receptor isoform on tumor cells have been successfully used for the delivery of various compounds and chemotherapeutic drugs to tumor vessels [30][31][32][33][34][35][36][37]. Peptides containing the cyclic CNGRC and linear GNGRG motifs have been applied for targeting tumor necrosis factor alpha (TNF-α) and interferon gamma [38][39][40][41].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery

Tripodi

Ranđelović

Szeder

et al. 2019

Pathol. Oncol. Res.

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Among various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro and in vivo antitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi's Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR to isoDGR in case of conjugate 2 (Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH 2) in comparison with conjugate 1 (Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH 2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.

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“…Using orthotopic transplantation, metastases were developed which showed specific 68 Ga-NOTA-c(NGR) uptake. [137] TRAP= (1,4,7-triazacyclononane-1,4,7-tris[(2-carboxyethyl)methylenephosphinic acid]), Glc= glucosyl , Gal=galactosyl , Mlt= maltosyl, Cel= cellobiosyl. NOPO= (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene-(2-carboxyethyl)phosphinic acid].…”

Section: C[kngre] -Nh2mentioning

confidence: 99%

Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection

Soudy

Byeon

Raghuwanshi

et al. 2017

MRMC

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Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide- receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized.

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

Cited by 46 publications

References 47 publications

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

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

In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery

Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection

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

Cited by 46 publications

References 47 publications

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

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

In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery

Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection

Contact Info

Product

Resources

About

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

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