68Ga-DOTA-NGR as a novel molecular probe for APN-positive tumor imaging using MicroPET

Zhang, Jun; Lü, Xiaoli; Wu, Nan; Hua, Zichun; Wang, Zizheng; Huang, Haifang; Yang, Min; Wang, Rui

doi:10.1016/j.nucmedbio.2013.12.008

Cited by 27 publications

(29 citation statements)

References 35 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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“…The asparagine-glycine-arginine (NGR) motif has been identified as an adequate ligand for CD13, displaying high affinity and specificity (26). It has been well established that, by labelling NGR peptide with 64 Cu or 68 Ga isotopes, the efficiency and specificity of NGR probes for the PET/CT imaging of CD13-positive tumors can be improved (27)(28)(29)(30). Therefore, we questioned whether the radio-labeled NGR probe could noninvasively image well-differentiated HCC tumors.…”

Section: The Uptake Exploration Of 68 Ga-labeled Ngr In Well-differenmentioning

confidence: 99%

The uptake exploration of 68Ga-labeled NGR in well-differentiated hepatocellular carcinoma xenografts: Indication for the new clinical translational of a tracer based on NGR

Gao

Wang

et al. 2017

Oncology Reports

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18F-FDG has low uptake and poor diagnostic efficiency in hepatocellular carcinoma (HCC), particularly in well-differentiated HCC. The NGR peptide selectively targets CD13, which is overexpressed in many types of tumor cells as well as neovasculature cells. In the present study, we aimed to evaluate the feasibility of utilizing 68Ga-NGR to image CD13-positive well-differentiated HCC xenografts. The in vitro cellular uptake, in vivo micro-PET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well‑differentiated HCC xenografts. The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) xenografts were respectively used as positive and negative reference groups for CD13. The expression of CD13 was qualitatively verified by immunofluorescence staining and immunohistostaining studies. The expression levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by western blotting. The in vitro SMMC-7721 cellular uptake of 68Ga‑NGR was significantly higher than that of 18F-FDG (1.23±0.11 vs. 0.515±0.14%; P<0.01). The in vivo micro-PET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721-derived tumors was 2.17±0.21% ID/g (percentage of injected dose per gram of tissue), which was higher compared to that of 18F-FDG (0.73±0.26% ID/g; P<0.01); however, the tumor/liver ratio of 68Ga-NGR was 2-fold higher than that of 18F-FDG. We concluded that the uptake of 68Ga-NGR was significantly higher both in vitro and in vivo than 18F-FDG in the well‑differentiated HCC xenografts and therefore, it is promising for further clinical translation in well-differentiated HCC PET/CT diagnosis.

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“…[11][12][13] The SPECT radioisotope, 99m Tc being routinely and widely used in clinics, occupies a premier position in nuclear medicine. These peptides have been radiolabeled with different isotopes ( 64 Cu, 68 Ga, and 99m Tc) for molecular imaging.…”

Section: Introductionmentioning

confidence: 99%

“…These peptides have been radiolabeled with different isotopes ( 64 Cu, 68 Ga, and 99m Tc) for molecular imaging. [11][12][13] The SPECT radioisotope, 99m Tc being routinely and widely used in clinics, occupies a premier position in nuclear medicine. 14,15 The predominance of Tc-99m is attributed to less expensive option of sourcing it from Mo-99/Tc-99m generator and the ideal nuclear properties (t 1/2 = 6 hr, 140 keV) that comply with the requirements of an ideal diagnostic isotope in clinical setting.…”

Section: Introductionmentioning

confidence: 99%

Preparation and comparative evaluation of ^99mTc‐HYNIC‐cNGR and ^99mTc‐HYNIC‐PEG₂‐cNGR as tumor‐targeting molecular imaging probes

Vats

Satpati

Sharma

et al. 2018

Labelled Comp Radiopharmac

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The tripeptide sequence asparagine-glycine-arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG -c(NGR), were synthesized, radiolabeled with Tc, and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, Tc-HYNIC-c(NGR) and Tc-HYNIC-PEG -c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being -2.33 ± 0.05 and -2.61 ± 0.08. The uptake of 2 radiotracers Tc-HYNIC-c(NGR) and Tc-HYNIC-PEG -c(NGR) was similar in nude mice bearing human fibrosarcoma HT-1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of Tc-labeled HYNIC peptide could not be modulated through introduction of PEG unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.

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68Ga-DOTA-NGR as a novel molecular probe for APN-positive tumor imaging using MicroPET

Cited by 27 publications

References 35 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

The uptake exploration of 68Ga-labeled NGR in well-differentiated hepatocellular carcinoma xenografts: Indication for the new clinical translational of a tracer based on NGR

Preparation and comparative evaluation of ^99mTc‐HYNIC‐cNGR and ^99mTc‐HYNIC‐PEG₂‐cNGR as tumor‐targeting molecular imaging probes

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68Ga-DOTA-NGR as a novel molecular probe for APN-positive tumor imaging using MicroPET

Cited by 27 publications

References 35 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

The uptake exploration of 68Ga-labeled NGR in well-differentiated hepatocellular carcinoma xenografts: Indication for the new clinical translational of a tracer based on NGR

Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes

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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

Preparation and comparative evaluation of ^99mTc‐HYNIC‐cNGR and ^99mTc‐HYNIC‐PEG₂‐cNGR as tumor‐targeting molecular imaging probes