Molecular Imaging and Biology

, Volume 13, Issue 5, pp 801–811 | Cite as

Current Evidence Base of FDG-PET/CT Imaging in the Clinical Management of Malignant Pleural Mesothelioma: Emerging Significance of Image Segmentation and Global Disease Assessment

  • Sandip Basu
  • Babak Saboury
  • Drew A. Torigian
  • Abass AlaviEmail author
Review Article


Increasingly, integrated positron emission tomography-computed tomography (PET/CT) imaging is playing a crucial role in the assessment of patients with known or suspected malignant pleural mesothelioma (MPM). Based on the data reported in the literature, this combined modality is likely to become the instrument of choice for examining patients of MPM. The research on this subject has focused on the following five domains: (1) differentiation of MPM from other benign pleural diseases, (2) preoperative staging for the selection of appropriate candidates for surgery, (3) evaluation for therapy response and post-treatment surveillance for recurrence, (4) prognostication based upon the intensity of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake, and (5) planning of radiotherapy. These represent the bases for critical decision making in the management of mesothelioma, and FDG-PET/CT offers potential advantages over conventional CT imaging and thus can play a pivotal role in this regard. Optimal characterization of this potentially fatal disease with a high negative predictive value for MPM, superior capability for cancer staging initially and at the later course of disease, and ability for measuring therapeutic response and the precise determination of the target volume for radiotherapy planning represent distinct advantages of this promising molecular imaging tool. In this communication, we have explored the promising role of integrated FDG-PET/CT in the overall management of this serious malignancy. From the available data, the major role of PET-CT at present appears to be in the preoperative disease staging, response to treatment assessment, and post-treatment disease surveillance of MPM. In all these three areas, PET-CT convincingly shows better results than conventional anatomical imaging alone and thereby can aid in exploring novel therapeutic approaches. Disease prognosis and radiotherapy planning are evolving areas where this modality has demonstrated significant promise, but this has to be investigated further. The differentiating of MPM from benign pleural disease is a challenging issue; though in limited studies, it has shown promising results, single standardized uptake value (SUV) cutoff technique cannot be the optimal way for this purpose. Dual time point and delayed imaging helps further in this setting; however, more data require to be accrued in this area. We, in this review, have also discussed the feasibility of a new method of image segmentation based on an iterative thresholding algorithm, which permits definition of the boundaries of lesions based on PET images alone to provide lesional metabolically active tumor volumes, lesional partial volume corrected SUV (PVC-SUV) measurements, lesional PVC metabolic burden (PVC-MB) (calculated as the product of lesional MVP and lesional PVC-SUV), and whole body metabolic burden (WBMB) (calculated as the sum of lesional PVC-MB of all lesions). This global disease assessment, we believe, will be the way forward for assessing this malignancy with a non-invasive imaging modality.

Key Words

PET PET/CT Mesothelioma FDG Pleural mesothelioma Malignant pleural mesothelioma 


Conflict of Interest Statement

The authors declare no conflict of interest.


  1. 1.
    Antman KH (1993) Natural history and epidemiology of malignant mesothelioma. Chest 103(4 Suppl):373S–376SPubMedCrossRefGoogle Scholar
  2. 2.
    Pisani RJ, Colby TV, Williams DE (1988) Malignant mesothelioma of the pleura. Mayo Clin Proc 63(12):1234–1244PubMedGoogle Scholar
  3. 3.
    Peto J, Decarli A, La Vecchia C, Levi F, Negri E (1999) The European mesothelioma epidemic. Br J Cancer 79:666–672PubMedCrossRefGoogle Scholar
  4. 4.
    Vogelzang NJ (2005) Standard therapy for the treatment of malignant pleural mesothelioma. Lung Cancer 50(Suppl 1):S23–S24PubMedCrossRefGoogle Scholar
  5. 5.
    Vogelzang NJ, Rusthoven JJ, Symanowski J et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636–2644PubMedCrossRefGoogle Scholar
  6. 6.
    O'Brien ME, Watkins D, Ryan C et al (2006) A randomised trial in malignant mesothelioma (M) of early (E) versus delayed (D) chemotherapy in symptomatically stable patients: the MED trial. Ann Oncol 17:270–275PubMedCrossRefGoogle Scholar
  7. 7.
    Yildirim H, Metintas M, Entok E, Ak G, Ak I, Dundar E, Erginel S (2009) Clinical value of fluorodeoxyglucose-positron emission tomography/computed tomography in differentiation of malignant mesothelioma from asbestos-related benign pleural disease: an observational pilot study. J Thorac Oncol 4(12):1480–1484PubMedCrossRefGoogle Scholar
  8. 8.
    Orki A, Akin O, Tasci AE, Ciftci H, Urek S, Falay O, Kutlu CA (2009) The role of positron emission tomography/computed tomography in the diagnosis of pleural diseases. Thorac Cardiovasc Surg 57(4):217–221, Epub 2009 May 20PubMedCrossRefGoogle Scholar
  9. 9.
    Rusch VW (1995) A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest 108:1122–1128PubMedCrossRefGoogle Scholar
  10. 10.
    Sugarbaker DJ, Flores RM, Jaklitsch MT et al (1999) Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 117:54–63, discussion 63-55PubMedCrossRefGoogle Scholar
  11. 11.
    Leung AN, Muller NL, Miller RR (1990) CT in differential diagnosis of diffuse pleural disease. AJR Am J Roentgenol 154:487–492PubMedGoogle Scholar
  12. 12.
    Heelan RT, Rusch VW, Begg CB, Panicek DM, Caravelli JF, Eisen C (1999) Staging of malignant pleural mesothelioma: comparison of CT and MR imaging. AJR Am J Roentgenol 172(4):1039–1047PubMedGoogle Scholar
  13. 13.
    Marom EM, Erasmus JJ, Pass HI, Patz EF Jr (2002) The role of imaging in malignant pleural mesothelioma. Semin Oncol 29(1):26–35PubMedCrossRefGoogle Scholar
  14. 14.
    Armato SG 3rd, Entwisle J, Truong MT et al (2008) Current state and future directions of pleural mesothelioma imaging. Lung Cancer 59:411–420PubMedCrossRefGoogle Scholar
  15. 15.
    Wang ZJ, Reddy GP, Gotway MB et al (2004) Malignant pleural mesothelioma: evaluation with CT, MR imaging, and PET. Radiographics 24:105–119PubMedCrossRefGoogle Scholar
  16. 16.
    Schneider DB, Clary-Macy C, Challa S, Sasse KC, Merrick SH, Hawkins R, Caputo G, Jablons D (2000) Positron emission tomography with f18-fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 120(1):128–133PubMedCrossRefGoogle Scholar
  17. 17.
    Flores RM, Akhurst T, Gonen M, Larson SM, Rusch VW (2003) Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg 126(1):11–16PubMedCrossRefGoogle Scholar
  18. 18.
    Benard F, Sterman D, Smith RJ, Kaiser LR, Albelda SM, Alavi A (1998) Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography. Chest 114(3):713–722PubMedCrossRefGoogle Scholar
  19. 19.
    Gerbaudo VH, Britz-Cunningham S, Sugarbaker DJ, Treves ST (2003) Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural mesothelioma. Thorax 58(12):1077–1082PubMedCrossRefGoogle Scholar
  20. 20.
    Dizendorf EV, Baumert BG, von Schulthess GK, Lutolf UM, Steinert HC (2003) Impact of whole-body 18F-FDG PET on staging and managing patients for radiation therapy. J Nucl Med 44:24–29PubMedGoogle Scholar
  21. 21.
    Cohade C, Osman M, Marshall LN, Wahl RN (2003) PET-CT: accuracy of PET and CT spatial registration of lung lesions. Eur J Nucl Med Mol Imaging 30:721–726PubMedCrossRefGoogle Scholar
  22. 22.
    Lardinois D, Weder W, Hany TF et al (2003) Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348:2500–2507PubMedCrossRefGoogle Scholar
  23. 23.
    von Schulthess GK, Steinert HC, Hany TF (2006) Integrated PET/CT: current applications and future directions. Radiology 238:405–422CrossRefGoogle Scholar
  24. 24.
    Erasmus JJ, Truong MT, Smythe WR et al (2005) Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: staging implications. J Thorac Cardiovasc Surg 129:1364–1370PubMedCrossRefGoogle Scholar
  25. 25.
    Plathow C, Staab A, Schmaehl A, Aschoff P, Zuna I, Pfannenberg C, Peter SH, Eschmann S, Klopp M (2008) Computed tomography, positron emission tomography, positron emission tomography/computed tomography, and magnetic resonance imaging for staging oflimited pleural mesothelioma: initial results. Invest Radiol 43(10):737–744PubMedCrossRefGoogle Scholar
  26. 26.
    Sorensen JB, Ravn J, Loft A, Brenøe J, Berthelsen AK (2008) Preoperative staging of mesothelioma by 18F-fluoro-2-deoxy-D-glucose positron emissiontomography/computed tomography fused imaging and mediastinoscopy compared to pathological findings after extrapleural pneumonectomy. Eur J Cardiothorac Surg 34(5):1090–1096, Epub 2008 Sep 16PubMedCrossRefGoogle Scholar
  27. 27.
    Wilcox BE, Subramaniam RM, Peller PJ, Aughenbaugh GL, Nichols FC III, Aubry MC, Jett JR (2009) Utility of integrated computed tomography-positron emission tomography for selection of operable malignant pleural mesothelioma. Clin Lung Cancer 10(4):244–248PubMedCrossRefGoogle Scholar
  28. 28.
    Ambrosini V, Rubello D, Nanni C, Farsad M, Castellucci P, Franchi R, Fabbri M, Rampin L, Crepaldi G, Al-Nahhas A, Fanti S (2005) Additional value of hybrid PET/CT fusion imaging vs. conventional CT scan alonein the staging and management of patients with malignant pleural mesothelioma. Nucl Med Rev Cent East Eur 8(2):111–115PubMedGoogle Scholar
  29. 29.
    Tan C, Barrington S, Rankin S, Landau D, Pilling J, Spicer J, Cane P, Lang-Lazdunski L (2010) Role of integrated 18-fluorodeoxyglucose position emission tomography-computed tomography in patients surveillance after multimodality therapy of malignant pleural mesothelioma. J Thorac Oncol 5(3):385–388PubMedCrossRefGoogle Scholar
  30. 30.
    Hicks RJ, Mac Manus MP, Matthews JP et al (2004) Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation. Int J Radiat Oncol Biol Phys 60:412–418PubMedCrossRefGoogle Scholar
  31. 31.
    Berriolo-Riedinger A, Touzery C, Riedinger JM et al (2007) [(18)F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 34:1915–1924PubMedCrossRefGoogle Scholar
  32. 32.
    Byrne MJ, Nowak AK (2004) Modified RECIST criteria for assessment of response inmalignant pleural mesothelioma. Ann Oncol 15(2):257–260PubMedCrossRefGoogle Scholar
  33. 33.
    Veit-Haibach P, Schaefer NG, Steinert HC, Soyka JD, Seifert B, Stahel RA (2010) Combined FDG-PET/CT in response evaluation of malignant pleural mesothelioma. Lung Cancer 67(3):311–317, Epub 2009 May 30PubMedCrossRefGoogle Scholar
  34. 34.
    Ceresoli GL, Chiti A, Zucali PA et al (2006) Early response evaluation in malignant pleural mesothelioma by positron emission tomography with [18F]fluorodeoxyglucose. J Clin Oncol 24:4587–4593PubMedCrossRefGoogle Scholar
  35. 35.
    Chang CL, Wu TC, Hung CF (2007) Control of human mesothelin-expressing tumors by DNA vaccines. Gene Ther 14:1189–1198PubMedCrossRefGoogle Scholar
  36. 36.
    Francis RJ, Byrne MJ, van der Schaaf AA et al (2007) Early prediction of response to chemotherapy and survival in malignant pleural mesothelioma using a novel semiautomated 3-dimensional volume-based analysis of serial 18F-FDG PET scans. J Nucl Med 48:1449–1458PubMedCrossRefGoogle Scholar
  37. 37.
    Lee ST, Ghanem M, Herbertson RA, Berlangieri SU, Byrne AJ, Tabone K, MitchellP KSR, Feigen M, Scott AM (2009) Prognostic value of 18F-FDG PET/CT in patients with malignant pleural mesothelioma. Mol Imaging Biol 11(6):473–479PubMedCrossRefGoogle Scholar
  38. 38.
    Krüger S, Pauls S, Mottaghy FM, Buck AK, Schelzig H, Hombach V, Reske SN (2007) Integrated FDG PET-CT imaging improves staging in malignant pleural mesothelioma. Nuklearmedizin 46(6):239–243PubMedGoogle Scholar
  39. 39.
    Pehlivan B, Topkan E, Onal C, Nursal GN, Yuksel O, Dolek Y, Yavuz MN, Yavuz AA (2009) Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma. Radiat Oncol 4:35PubMedCrossRefGoogle Scholar
  40. 40.
    Powell A, Creaney J, Broomfield S, Van Bruggen I, Robinson B (2006) Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with mesothelioma. Lung Cancer 52:189–197PubMedCrossRefGoogle Scholar
  41. 41.
    Vachani A, Sterman DH, Albelda SM (2007) Cytokine gene therapy for malignant pleural mesothelioma. J Thorac Oncol 2:265–267PubMedCrossRefGoogle Scholar
  42. 42.
    Sterman DH, Recio A, Carroll RG et al (2007) A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res 13:4456–4466PubMedCrossRefGoogle Scholar
  43. 43.
    Mankoff DA, Shields AF, Krohn KA (2005) PET imaging of cellular proliferation. Radiol Clin North Am 43:153–167PubMedCrossRefGoogle Scholar
  44. 44.
    Lucignani G (2008) PET imaging with hypoxia tracers: a must in radiation therapy. Eur J Nucl Med Mol Imaging 35(4):838–842PubMedCrossRefGoogle Scholar
  45. 45.
    Basu S, Alavi A (2009) Molecular imaging (PET) of brain tumors. Neuroimaging Clin N Am 19(4):625–646PubMedCrossRefGoogle Scholar
  46. 46.
    Tsuji AB, Sogawa C, Sugyo A, Sudo H, Toyohara J, Koizumi M, Abe M, Hino O, Harada YN, Furukawa T, Suzuki K, Saga T (2009) Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts. Nucl Med Biol 36(4):379–388PubMedCrossRefGoogle Scholar
  47. 47.
    Alavi A, Newberg AB, Souder E, Berlin JA (1993) Quantitative analysis of PET and MRI data in normal aging and Alzheimer’s disease: atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators. J Nucl Med 34(10):1681–1687PubMedGoogle Scholar
  48. 48.
    Bural GG, Torigian DA, Chamroonrat W, Alkhawaldeh K, Houseni M, El-Haddad G, Alavi A (2006) Quantitative assessment of the atherosclerotic burden of the aorta by combined FDG-PET and CT image analysis: a new concept. Nucl Med Biol 33(8):1037–1043PubMedCrossRefGoogle Scholar
  49. 49.
    Berkowitz A, Basu S, Srinivas S, Sankaran S, Schuster S, Alavi A (2008) Determination of whole-body metabolic burden as a quantitative measure of disease activity in lymphoma: a novel approach with fluorodeoxyglucose-PET. Nucl Med Commun 29(6):521–526PubMedCrossRefGoogle Scholar
  50. 50.
    Bural GG, Torigian DA, Burke A, Houseni M, Alkhawaldeh K, Cucchiara A, Basu S, Alavi A (2010) Quantitative assessment of the hepatic metabolic volume product in patients with diffuse hepatic steatosis and normal controls through use of FDG-PET and MR imaging: a novel concept. Mol Imaging Biol 12(3):233–239PubMedCrossRefGoogle Scholar
  51. 51.
    Basu S, Zaidi H, Houseni M, Bural G, Udupa J, Acton P, Torigian DA, Alavi A (2007) Novel quantitative techniques for assessing regional and global function and structure based on modern imaging modalities: implications for normal variation, aging and diseased states. Semin Nucl Med 37(3):223–239PubMedCrossRefGoogle Scholar
  52. 52.
    Hofheinz F, Pötzsch C, van den Hoff J (2007) Quantxtative 3D ROI delineation in PET: algorithm and validation. J Nucl Med 48:407PGoogle Scholar
  53. 53.
    Benard F, Sterman D, Smith RJ, Kaiser LR, Albelda SM, Alavi A (1999) Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med 40:1241–1245PubMedGoogle Scholar
  54. 54.
    Mavi A, Basu S, Cermik TF, Urhan M, Bathaii M, Thiruvenkatasamy D, Houseni M, Dadparvar S, Alavi A (2009) XPotential of dual time point FDG-PET imaging in differentiating malignant from benign pleural disease. Mol Imaging Biol 11(5):369–378, Epub 2009 May 27PubMedCrossRefGoogle Scholar

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Sandip Basu
    • 1
  • Babak Saboury
    • 2
  • Drew A. Torigian
    • 2
  • Abass Alavi
    • 2
    Email author
  1. 1.Radiation Medicine Center (Bhabha Atomic Research Center)Tata Memorial Hospital AnnexeParelIndia
  2. 2.Division of Nuclear Medicine, Department of RadiologyHospital of the University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations