Pharmacokinetic analysis of malignant pleural mesothelioma-initial results of tumor microcirculation and its correlation to microvessel density (CD-34).
OBJECTIVE
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.


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, k(ep), k(el)), 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 < or = .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.
Giesel
Frederik L
FL
Radiologie, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany. f.giesel@egiesel.com
Choyke
Peter L
PL
Mehndiratta
Amit
A
Zechmann
Christian M
CM
von Tengg-Kobligk
Henrik
H
Kayser
Klaus
K
Bischoff
Helge
H
Hintze
Christian
C
Delorme
Stefan
S
Weber
M A
MA
Essig
Marco
M
Kauczor
Hans-Ulrich
HU
Knopp
Michael V
MV
D000368:Aged; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008654:Mesothelioma / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008833:Microcirculation; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology
D003287:Contrast Media; D019786:Gadolinium DTPA