<sup>111</sup>In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

Kumar, Sudeep; Deutscher, Susan L.

doi:10.2967/jnumed.107.048751

Cited by 45 publications

(27 citation statements)

References 29 publications

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“…Both 111 In and 64 Cu labeled DOTA-AgRP-7C exhibit high renal uptake, which is likely attributed to (1) the long residence time of radiometabolites produced by lysosomal degradation of the radiolabeled peptides within renal cells; (2) the overall positive charge of the peptides [22–25]. Several strategies previously reported that the accumulation of radiopeptide in the kidneys can be effectively reduced by coinjection of cationic amino acid such as lysine, or poly-lysine molecules [16, 26].…”

Section: Discussionmentioning

confidence: 99%

I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

Jiang

Miao

Kimura

et al. 2012

Journal of Biomedicine and Biotechnology

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Agouti-related protein (AgRP) is a 4-kDa cystine-knot peptide of human origin with four disulfide bonds and four solvent-exposed loops. The cell adhesion receptor integrin αvβ3 is an important tumor angiogenesis factor that determines the invasiveness and metastatic ability of many malignant tumors. AgRP mutants have been engineered to bind to integrin αvβ3 with high affinity and specificity using directed evolution. Here, AgRP mutants 7C and 6E were radiolabeled with 111In and evaluated for in vivo targeting of tumor integrin αvβ3 receptors. AgRP peptides were conjugated to the metal chelator 1, 4, 7, 10-tetra-azacyclododecane- N, N′, N″, N‴-tetraacetic acid (DOTA) and radiolabeled with 111In. The stability of the radiopeptides 111In-DOTA-AgRP-7C and 111In-DOTA-AgRP-6E was tested in phosphate-buffered saline (PBS) and mouse serum, respectively. Cell uptake assays of the radiolabeled peptides were performed in U87MG cell lines. Biodistribution studies were performed to evaluate the in vivo performance of the two resulting probes using mice bearing integrin-expressing U87MG xenograft tumors. Both AgRP peptides were easily labeled with 111In in high yield and radiochemical purity (>99%). The two probes exhibited high stability in phosphate-buffered saline and mouse serum. Compared with 111In-DOTA-AgRP-6E, 111In-DOTA-AgRP-7C showed increased U87MG tumor uptake and longer tumor retention (5.74 ± 1.60 and 1.29 ± 0.02%ID/g at 0.5 and 24 h, resp.), which was consistent with measurements of cell uptake. Moreover, the tumor uptake of 111In-DOTA-AgRP-7C was specifically inhibited by coinjection with an excess of the integrin-binding peptidomimetic c(RGDyK). Thus, 111In-DOTA-AgRP-7C is a promising probe for targeting integrin αvβ3 positive tumors in living subjects.

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Section: Discussionmentioning

confidence: 99%

I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

Jiang

Miao

Kimura

et al. 2012

Journal of Biomedicine and Biotechnology

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“…During the last decade, there has been an increasing interest for the use of non-biogenic positron emitters, such as 64 Cu (T 1/2 = 12.7 h), 68 Ga (T 1/2 = 1.14 h), 76 Br (T 1/2 = 16.2 h), 86 Y (T 1/2 = 14.7 h), 89 Zr (T 1/2 = 78.4 h), and 124 I (T 1/2 = 100.2 h) ( Table 2), for labelling of targeting peptides and Mabs [33 -35]. Long-lived positron-emitting nuclides have widened a time window of PET up to several days, making it possible to utilise advantages of this detection technique for imaging using tracers with longer residence time in the circulation.…”

Section: Radionuclide-based Imaging Methodsmentioning

confidence: 99%

“…Phage display technology makes it possible to select peptides, such as G3-C12 (ANTPC GPYTHDCPVKR), which binds to galectins in prostate cancer [75] and breast cancer [76] cell lines, KCCYSL, which is capable of targeting HER2 expressing cell lines in vivo [77], breast cancer targeting peptide p160 (VPWMEPAYQRFL) [78] and prostate-targeting peptides DUP-1 (FRPNRAQD YNTN) [79] and FROP-1 (EDYELMDLLAYL) [81,82], which bind the targets with affinities ranging for micromol to hundreds of nanomol. Generally, the peptides demonstrated rapid clearance from the majority of organs and tissues.…”

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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Section: Figures and Tablesmentioning

confidence: 99%

Phage Display in Molecular Imaging and Diagnosis of Cancer

2010

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¹¹¹In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

Cited by 45 publications

References 29 publications

I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

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

Phage Display in Molecular Imaging and Diagnosis of Cancer

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111In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

Cited by 45 publications

References 29 publications

I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

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

Phage Display in Molecular Imaging and Diagnosis of Cancer

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Product

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¹¹¹In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors