Radiohalogenated 4-anilinoquinazoline-based EGFR-TK inhibitors as potential cancer imaging agents

Neto, Carina; Fernandes, Célia; Oliveira, Maria Cristina; Gano, Lurdes; Mendes, Filipa; Knieß, Torsten; Santos, Isabel

doi:10.1016/j.nucmedbio.2011.09.001

Cited by 11 publications

(14 citation statements)

References 40 publications

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“…Some noninvasive molecular agents, such as 11 Cerlotinib, 11 C-labeled 4-N-(3-bromoanilino)-6, 7-dimethoxyquinazoline, 177 Lu-nimotuzumab, 18 F-labeled Affibody protein, or anti-EGFR monoclonal antibodies using contrast-enhanced MR imaging, have been developed as molecular imaging biomarkers for evaluating tumor EGFR status (17)(18)(19)(20)(21). Although these EGFR-specific imaging probes have been investigated, they all have been directed either at an external ligand binding domain using antibodies and Affibody molecules or at the internal adenosine triphosphate binding domain with small organic reversible and irreversible inhibitors (22).…”

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confidence: 99%

Preparation and Evaluation of ^99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

et al. 2014

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Epidermal growth factor receptor (EGFR) is overexpressed in many carcinomas and remains a prime target for diagnostic and therapeutic applications. There is a need to develop noninvasive methods to identify the subset of patients that is most likely to benefit from EGFR-targeted treatment. Noninvasive imaging of EGFR messenger RNA (mRNA) expression may be a useful approach. The aim of this study was to develop a method for preparation of single-photon-emitting probes, 99m Tc-labeled EGFR mRNA antisense peptide nucleic acid (PNA) ( 99m Tc-EGFR-PNA), and nontargeting control ( 99m Tc-CTL-PNA) and to evaluate their feasibility for imaging EGFR mRNA overexpression in malignant tumors in vivo. Methods: On the 5′ terminus of synthesized singlestranded 17-mer antisense EGFR mRNA antisense PNA and mismatched PNA, a 4-amino-acid (Gly-(D)-Ala-Gly-Gly) linker forming an N 4 structure was used for coupling 99m Tc. Probes were labeled with 99m Tc by ligand exchange. The radiochemical purity of these 99m Tc-labeled probes was determined by reversed-phase high-performance liquid chromatography. Cellular uptake, retention, binding specificity, and stability of the probes were studied either in vitro or in vivo. Biodistribution and radionuclide imaging were performed in BALB/c nude mice bearing SKOV3 (EGFR-positive) or MDA-MB-435S (EGFR-negative) carcinoma xenografts, respectively. Results: The average labeling efficiencies of 99m Tc-EGFR-PNA and 99m Tc-CTL-PNA were 98.80% ± 1.14% and 98.63% ± 1.36% (mean ± SD, n 5 6), respectively, within 6 h at room temperature, and the radiochemical purity of the probes was higher than 95%. 99m Tc-EGFR-PNA was highly stable in normal saline and fresh human serum at 37°C in vitro and in urine and plasma samples of nude mice after 2-3 h of injection. Cellular uptake and retention ratios of 99m Tc-EGFR-PNA in SKOV3 cells were higher than those of 99m Tc-CTL-PNA and the EGFR-negative control. Meanwhile, EGFR mRNA binding 99m Tc-EGFR-PNA was blocked with an excess of unlabeled EGFR-PNA in SKOV3 cell lines. The biodistribution study demonstrated accumulation of 99m Tc-EGFR-PNA primarily in the SKOV3 xenografts and in EGFR-expressing organs. Radionuclide imaging demonstrated clear localization of 99m Tc-EGFR-PNA in the SKOV3 xenografts shortly after injection but not in 99m Tc-CTL-PNA and the EGFR-negative control. Conclusion: 99m Tc-EGFR-PNA has the potential for imaging EGFR mRNA overexpression in tumors.

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Preparation and Evaluation of ^99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

et al. 2014

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“…Other novel radiolabelled small molecules, such as labelled growth factor receptor tyrosine kinase inhibitors, used primarily to study the pharmacokinetic behaviour of this recent class of cancer medicines, can equally diffuse through the cell membrane to reach intracellular targets . These were recently reviewed …”

Section: Techniques: How To Image Intracellular/intranuclear Targetsmentioning

confidence: 99%

Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

Cornelissen

2014

Labelled Comp Radiopharmac

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Molecular imaging of tumour tissue focusses mainly on extracellular epitopes such as tumour angiogenesis or signal transduction receptors expressed on the cell membrane. However, most biological processes that define tumour phenotype occur within the cell. In this mini-review, an overview is given of the various techniques to interrogate intracellular events using molecular imaging with radiolabelled compounds. Additionally, similar targeting techniques can be employed for radionuclide therapy using Auger electron emitters, and recent advances in Auger electron therapy are discussed.

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“…To address this issue of in vivo instability, the incorporation of 125 I and 18 F into molecules similar to 38 but bearing an aromatic side chain was investigated. 46 The synthesis of three such derivatives with a C6 radiohalogenated benzamide side chain ( Fig. 6) was accomplished by the reaction of aryl amine 19 with benzoyl chloride derivatives to yield 22a-b and 27.…”

Section: Small-molecule Inhibitors Featuring a Radiohalogenated C6mentioning

confidence: 99%

Imaging EGFR and HER2 by PET and SPECT: A Review

Corcoran

Hanson

2013

Medicinal Research Reviews

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In an effort to discover a noninvasive method for predicting which cancer patients will benefit from therapy targeting the EGFR and HER2 proteins, a large body of the research has been conducted toward the development of PET and SPECT imaging agents, which selectively target these receptors. We provide a general overview of the advances made toward imaging EGFR and HER2, detailing the investigation of PET and SPECT imaging agents ranging in size from small molecules to monoclonal antibodies.

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Radiohalogenated 4-anilinoquinazoline-based EGFR-TK inhibitors as potential cancer imaging agents

Cited by 11 publications

References 40 publications

Preparation and Evaluation of ^99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

Preparation and Evaluation of ^99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

Imaging EGFR and HER2 by PET and SPECT: A Review

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Radiohalogenated 4-anilinoquinazoline-based EGFR-TK inhibitors as potential cancer imaging agents

Cited by 11 publications

References 40 publications

Preparation and Evaluation of 99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

Preparation and Evaluation of 99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

Imaging EGFR and HER2 by PET and SPECT: A Review

Contact Info

Product

Resources

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Preparation and Evaluation of ^99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors

Preparation and Evaluation of ^99mTc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors