Academic Radiology
Volume 15, Issue 5 , Pages 563-570, May 2008

Pharmacokinetic Analysis of Malignant Pleural Mesothelioma—Initial Results of Tumor Microcirculation and its Correlation to Microvessel Density (CD-34)

  • Frederik L. Giesel, MD, MBA

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • Ohio State University, Columbus, OH.
    • Corresponding Author InformationAddress correspondence to: F.L.G.
    • ,
  • Peter L. Choyke, MD

      Affiliations

    • Molecular Imaging Program, NIH, Bethesda, MD
    • ,
  • Amit Mehndiratta, MBBS

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • School of Medical Science and Technology, IIT, Kharagpur, India
    • ,
  • Christian M. Zechmann, MD

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Henrik von Tengg-Kobligk, MD

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Klaus Kayser, MD

      Affiliations

    • UICC-TPCC, Institute of Pathology, Charite, Berlin, Germany
    • ,
  • Helge Bischoff, MD

      Affiliations

    • Radiotherapy and Biomedicine, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Christian Hintze, MD

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Stefan Delorme, MD

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • M.A. Weber, MD, MSc

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Marco Essig, MD

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Hans-Ulrich Kauczor, MD

      Affiliations

    • Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany
    • ,
  • Michael V. Knopp, MD, PhD

      Affiliations

    • Ohio State University, Columbus, OH.

Received 29 October 2007; accepted 13 December 2007.

Rationale and Objectives

Malignant mesothelioma (MM) of the pleura is an aggressive and often fatal neoplasm. Because MM frequently demonstrates marked angiogenesis, it may be responsive to antiangiogenic therapy, but effective methods for selecting and monitoring of patients are further needed. We employed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative immunohistochemistry (IHC) to characterize the microvascularity of MM using both a physiologic and ultrastructural method.

Materials and Methods

Nineteen patients diagnosed with MM were enrolled and DCE-MRI was performed before antiangiogenic treatment. For each patient, tumor regions were characterized by their DCE-MRI–derived pharmacokinetic parameters (Amp, kep, kel), which were also compared to those of normal tissue (aorta, liver, spleen, and muscle). In addition, quantitative IHC of representative samples was performed with CD-34 staining to compare the calculated microvessel density (MVD) results with DCE-MRI results.

Results

MM demonstrated markedly abnormal pharmacokinetic properties compared with normal tissues. Among the parameters tested, Amp was significantly different in MM (P ≤ .001) compared to normal organs. Despite the observation that the MVD of mesotheliomas in this series was high compared to other tumors, DCE-MRI pharmacokinetic parameters had a moderately positive correlation with MVD (r = 0.5).

Conclusions

DCE-MRI and IHC can be used in patients with MM to visualize tumor microvascularity and to characterize tumor heterogeneity. DCE-MRI and IHC results positively correlated, though moderately, but these two methods present as essential tumor biomarkers. This multimodal characterization may be useful in selecting possible tumor subtypes that would benefit from antiangiogenic therapy.

Key Words: Angiogenesis, malignant mesothelioma, dynamic contrast enhanced MRI, pharmacokinetic analysis, microvascular density, CD-34

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PII: S1076-6332(07)00717-9

doi:10.1016/j.acra.2007.12.014

Academic Radiology
Volume 15, Issue 5 , Pages 563-570, May 2008

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