68Ga-EMP-100 PET/CT—a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma—first in-human biodistribution and imaging results.

Background: 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging...

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Publicado en:European Journal of Nuclear Medicine & Molecular Imaging Vol. 49; no. 5; pp. 1711 - 1721
Autores principales: Mittlmeier, Lena M., Todica, Andrei, Gildehaus, Franz-Josef, Unterrainer, Marcus, Beyer, Leonie, Brendel, Matthias, Albert, Nathalie L., Ledderose, Stephan T., Vettermann, Franziska J., Schott, Melanie, Rodler, Severin, Marcon, Julian, Ilhan, Harun, Cyran, Clemens C., Stief, Christian G., Staehler, Michael, Bartenstein, Peter
Formato: research tables/charts Journal Article
Publicado: Springer Nature Apr2022
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2022
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00259-021-05596-6
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        atl: 68Ga-EMP-100 PET/CT—a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma—first in-human biodistribution and imaging results.
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        au:
          Mittlmeier, Lena M.
          Todica, Andrei
          Gildehaus, Franz-Josef
          Unterrainer, Marcus
          Beyer, Leonie
          Brendel, Matthias
          Albert, Nathalie L.
          Ledderose, Stephan T.
          Vettermann, Franziska J.
          Schott, Melanie
          Rodler, Severin
          Marcon, Julian
          Ilhan, Harun
          Cyran, Clemens C.
          Stief, Christian G.
          Staehler, Michael
          Bartenstein, Peter
        affil: Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
      sug:
        subj:
          Positron-Emission Tomography Methods
          Tomography, X-Ray Computed Methods
          Carcinoma, Renal Cell Physiopathology
          Neoplasm Metastasis Physiopathology
          Ligands Physiology
          Neoplasm Staging
          Protein-Tyrosine Kinases Physiology
          Antineoplastic Agents Therapeutic Use
          Human
          Neoplasms Metabolism
          Descriptive Statistics
          Liver Neoplasms
          Bladder Pathology
          Kidney Pathology
          Spleen Pathology
          Pancreas Pathology
      ab: Background: 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. Methods: Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. Results: Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86–29.16)), followed by bone metastases (SUVmax 5.56 (0.97–15.85)), and lymph node metastases (SUVmax 3.90 (2.13–6.28)) and visceral metastases (SUVmax 3.82 (0.11–16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. Conclusion: Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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