c-Met PET Imaging Detects Early-Stage Locoregional Recurrence of Basal-Like Breast Cancer

Arulappu, Appitha; Battle, Mark; Eisenblaetter, Michel; McRobbie, Graeme; Khan, Imtiaz Ahmed; Monypenny, James; Weitsman, Gregory; Galazi, Myria; Hoppmann, Susan; Gazinska, Patrycja; Wulaningsih, Wulan; Dalsgaard, Grethe Tang; Macholl, Sven; Ng, Tony

doi:10.2967/jnumed.115.164384

Cited by 26 publications

(21 citation statements)

References 28 publications

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“…The AH113804 peptide has also been labelled with 18 F for PET, and is able to detect recurrence of c-MET-expressing basal-like breast cancer xenografts after surgical resection [33]. A fluorescent labelled version of the same peptide has been used as a ‘red flag’ technique to detect polyps using a fluorescence endoscope technique in patients at risk of developing colon cancer [34].…”

Section: Discussionmentioning

confidence: 99%

89Zr-Onartuzumab PET imaging of c-MET receptor dynamics

Pool

Scheltinga

Kol

et al. 2017

Eur J Nucl Med Mol Imaging

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Purposec-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of 89Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts.MethodsIn vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent 89Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent 89Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results.ResultsIn vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, 89Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment.ConclusionThe results show that 89Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3672-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

89Zr-Onartuzumab PET imaging of c-MET receptor dynamics

Pool

Scheltinga

Kol

et al. 2017

Eur J Nucl Med Mol Imaging

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“…Based on these studies, in 2016, Arulappu et al developed a radiolabeled analogue of GE-137, 18 F-AH113804, synthesized with radiochemical purity of >90% and specific activity of 100 GBq/μmol [66]. After validating the high affinity and specific binding of 18 F-AH113804 to c-MET (Kd ≈ 2nM) by ex vivo analyses and PET imaging, Arulappu and colleagues demonstrated that 18 F-AH113804-based PET imaging could detect loco-regional recurrences after surgical excision of orthotopically implanted HCC1954 human basal-like breast cancer with high c-MET expression in mice models as early as 6 days postoperatively, while with CT scanning, the recurrences could only be visualized after at least 20 days.…”

Section: Reviewmentioning

confidence: 99%

Analysis of progress and challenges for various patterns of c-MET-targeted molecular imaging: a systematic review

Han

Wang

et al. 2017

EJNMMI Res

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BackgroundMesenchymal–epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis. c-MET-targeted therapies have been tested in preclinical models and patients, with significant benefits for cancer treatment. In recent years, many studies have shown that the expression level and activation status of c-MET are closely correlated to c-MET-targeted therapy response and clinical prognosis, thus highlighting the importance of evaluating the c-MET status during and prior to targeted therapy. Molecular imaging allows the monitoring of abnormal alterations of c-MET in real time and in vivo.ResultsIn this review, we initially summarize the recent advances in c-MET-targeted molecular imaging, with a special focus on the development of imaging agents ranging in size from monoclonal antibody to small molecule. The aim of this review is to report the preclinical results and clinical application of all molecular imaging studies completed until now for in vivo detection of c-MET in cancer, in order to be beneficial to development of molecular probe and the combination of molecular imaging technologies for in vivo evaluation of c-MET. Various molecular probe targeted to c-MET possesses distinctive advantages and disadvantages. For example, antibody-based probes have high binding affinity but with long metabolic cycle as well as remarkable immunogenicity.ConclusionsAlthough studies for c-MET-targeted molecular imaging have made many important advances, most of imaging agents specifically target to extracellular area of c-MET receptor; however, it is difficult to reflect entirely activation of c-MET. Therefore, small molecule probes based on tyrosine kinase inhibitors, which could target to intracellular area of c-MET without any immunogenicity, should be paid more attention.

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“…Small-molecule tracers continue to be well represented clinically (SI Table 1 [126][127][128][129] . On the one hand, because of their rapid pharmacokinetic profiles, small-molecule [130][131][132] and many peptide 133 -based tracers are well-suited to procedures involving sequential multiplexing. On the other hand, macromolecules 134 including antibodies and nanoparticles [135][136][137][138][139][140][141][142][143][144] , generally constitute versatile agents for simultaneously multiplexed imaging and therapeutic strategies.…”

Section: Combining Data From Different Molecular Contrastsmentioning

confidence: 99%

Multiplexed imaging for diagnosis and therapy

et al. 2017

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Complex molecular and metabolic phenotypes depict cancers as a constellation of different diseases with common themes. Precision imaging of such phenotypes requires flexible and tuneable modalities capable of identifying phenotypic fingerprints by using a restricted number of parameters whilst ensuring sensitivity to dynamic biological regulation. Common phenotypes can be detected by in vivo imaging technologies, and effectively define the emerging standards for disease classification and patient stratification in radiology. However, for the imaging data to accurately represent a complex fingerprint, the individual imaging parameters need to be measured and analysed in relation to their wider spatial and molecular context. In this respect, targeted palettes of molecular imaging probes facilitate the detection of heterogeneity in oncogene-driven alterations and their response to treatment, and lead to the expansion of rational-design elements for the combination of imaging experiments. In this Review, we evaluate criteria for conducting multiplexed imaging, and discuss its opportunities for improving patient diagnosis and the monitoring of therapy.

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c-Met PET Imaging Detects Early-Stage Locoregional Recurrence of Basal-Like Breast Cancer

Cited by 26 publications

References 28 publications

89Zr-Onartuzumab PET imaging of c-MET receptor dynamics

89Zr-Onartuzumab PET imaging of c-MET receptor dynamics

Analysis of progress and challenges for various patterns of c-MET-targeted molecular imaging: a systematic review

Multiplexed imaging for diagnosis and therapy

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