- Email: [email protected]
Positron emission tomography in the diagnosis of mesothelioma
Lung Cancer (2004) 45S, S73—S76
Positron emission tomography in the diagnosis of mesothelioma Uwe Haberkorn* Department of Nuclear Medicine, University of Heidelberg, German Cancer Research Center, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany
KEYWORDS Malignant pleural mesothelioma; Diffuse pleural thickening; CT; MRI; FDG-PET imaging
Summary The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies and a need for new diagnostic techniques to identify the extent of the disease at an early stage and to evaluate treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in identifying the location and extent of the involved areas but cannot always differentiate between benign and malignant processes. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging, which in oncology, is based on changes in metabolic pathways of glucose, has been shown in a number of studies to differentiate malign and benign lesions in patients with asbestos exposure. FDG-PET images were also found to provide excellent delineation of the active tumour sites. Further evaluations of this technique included a combined experimental/clinical study to investigate the difference in rates of FDG uptake between malignant and inflammatory cells and processes. © 2004 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The diagnosis and therapy of mesothelioma is still challenging. Currently, the best chance for long-term survival is achieved with early diagnosis and aggressive surgery, but due to the long delay between the onset of symptoms and the diagnosis, this is only possible with an extensive diagnosic workup. Aggressive surgery is required for optimal debulking, and extrapleural pneumonectomy may offer better local control compared with pleurectomy/ecortication. Delivery of optimal radiation schedules, which may involve large fractions as well as large total doses, is limited by the presence of nearby dose-limiting structures. * Tel.: +49-6221-567-731; fax: +49-6221-565-473. E-mail address: uwe [email protected] (U. Haberkorn).
Current chemotherapy only rarely leads to objective responses and improved survival, although gemcitabine and interleukin-2 (IL-2) may be active agents to be combined with radiation and/or other agents. Many of these techniques may provide greater benefit when used in the setting of adjuvant protocols or minimal residual disease, emphasising the importance of multimodality therapy [1]. The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies, which still need to be fully validated. This results in a need for new diagnostic techniques that can lead to a definite diagnosis and to a satisfactory evaluation of the response to treatment. Therefore, imaging procedures need to deliver an evaluation of the extent of a lesion, differential diagnosis between malignant and benign lesions, accurate staging and monitoring of therapy response.
0169-5002/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2004.04.016
S74
2. Imaging techniques Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in identifying the location and extent of the involved areas. However, diffuse pleural thickening can represent either a benign or a malignant process, particularly in asbestos-exposed workers. Diffuse pleural thickening is not specific and may be caused by asbestos exposure, as a consequence of haemorrhagic effusion or by a number of infectious processes such as tuberculosis or empyema. Therefore, the sensitivity and specificity of CT to predict the malignant nature of diffuse pleural lesions are 72 and 83% (MRI 100 and 87%). Scintigraphy with 67 Gallium shows a sensitivity of 86% and a specificity of 81%, but suffers from low resolution [2]. The combination of fine needle pleural biopsy and fluid cytology shows only a sensitivity of <40%. CT-guided pleural needle biopsy reaches 60% for a single biopsy and 85% for repeated biopsies [2]. In contrast, thoracoscopy has a sensitivity of >90% with a low mortality rate (<0.1%) but nonfatal complications in up to 10% of the patients (tumour seeding along the chest wall, empyema, haemorrhage, subcutaneous emphysema, wound infection). The method remains the primary diagnostic modality for mesothelioma, but this invasive approach cannot always accurately stage the mediastinal nodes or transdiaphragmatic extension.
3. FDG-PET imaging Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in oncology is based on changes in metabolic pathways of glucose. For glucose metabolism, three key enzymes for glycolysis (glucokinase, phosphofructokinase, pyruvate kinase) and four key enzymes for gluconeogenesis (glucose6-phosphatase, fructose-1,6,-diphosphatase, phosphoenolpyruvate carboxykinase, pyruvate carboxylase) were identified. The velocity and direction of these opposite metabolic pathways are determined by the amount and the activity of these enzymes. In tumours, glycolytic enzymes are upregulated, whereas the gluconeogenetic enzymes are downregulated. These changes are coupled to the progression of tumour development. Furthermore, changes in the pattern of the isoenzymes with prevalence of non-specific isoforms and high affinity (low Km ) occur. Furthermore, the type 1 glucose transporter (GLUT1) gene is seen as one of the early genes, which are activated early after transformation of cells with oncogenes such as src,
U. Haberkorn ras or fps. Consequently, an increased amount of types 1 and 3 GLUT mRNA has been demonstrated in a variety of human tumour tissues [3]. PET measurements of FDG accumulation in different animal tumours showed a correlation of tracer FDG uptake and the mRNA content of GLUT1 as well as the hexokinase [4]. Possible applications of PET for imaging of mesothelioma are: to detect and stage the extent, to differentiate between malignant and benign lesions in patients with asbestos exposure who present with atypical diffuse pleural thickening or pleural effusion with a normal CT scan, assessment of disease progression, and evaluation of disease response to treatment. However, at present only a few studies with a limited number of patients have been performed. Carretta et al studied 14 patients (10 with malignant pleural mesothelioma, three with other malignant tumours and one with benign disease) with CT scan evidence of pleural thickening, or fluid [5]. PET assessment demonstrated significant 18 FDG uptake in 12/13 patients with a malignant disease, also revealing distant metastases in two of them (overall accuracy of 92%). A false-negative result was observed in a patient with an epithelial mesothelioma and a benign pleural disease without significant uptake was correctly diagnosed in another patient. A similar study by Buchmann et al. [6] in 16 patients (four with benign pleural changes) revealed that all 12 pleural or intrapulmonal malignant tumours had high FDG-uptake and were classified correctly. The four histologically benign lesions were correctly interpreted as nonmalignant due to their low FDG accumulation. Benard et al. [2] examined the value of FDG-PET for the differentiation between malignant versus benign lesions in 28 patients (24 with malignant disease). The uptake of FDG was significantly higher in malignant than in benign lesions. With a cut off value of 2.0 for FDG uptake to differentiate between malignant and benign disease, a sensitivity of 91% and a specificity of 100% could be achieved, although the activity in some epithelial mesotheliomas tended to be close to this threshold indicating that there is a potential overlap between mesothelioma with low FDG uptake and severe pleural inflammation. Also the limited number of patients with benign disease in this study precludes definitive statements. FDG-PET images provided excellent delineation of the active tumour sites. Hypermetabolic lymph node involvement was noted on FDG-PET images in 12 patients, nine of which appeared normal on CT scans. Histologic examination in six patients confirmed malignant nodal disease in five cases and indicated granulomatous lymphadenitis in one. In a study population of 18 pa-
Positron emission tomography in the diagnosis of mesothelioma tients two false-positive results were observed: increased FDG uptake in the contralateral chest that was negative by thoracoscopic biopsy and increased abdominal FDG uptake after partial colectomy for diverticular disease [7]. Identification of occult extrathoracic metastases by positron emission tomography was the basis for excluding two patients from surgical therapy [7]. Since mesotheliomas can involve very diffusely the parietal pleura with a thin layer of malignant cells partial volume effects may be a problem. The tumours represent irregular sheet-like lesions of uncertain thickness which makes a correction as done with spherical tumours more challenging. This may cause problems for the differential diagnosis of small lesions. A combined experimental/clinical study investigated the difference in the rates of FDG uptake between malignant and inflammatory cells and processes [8]. In vitro studies of the FDG uptake in different tumour cell lines (human mesothelioma; rat mesothelioma; mice melanoma; mice mesothelioma; human myeloma; and human ovarian cancer) and peripheral blood mononuclear cells isolated from eight healthy human volunteers revealed a significantly increased FDG uptake in most tumour cell lines over time, whereas the FDG uptake in mononuclear cells was decreased in seven of eight donors. In animal studies with rat mesothelioma and focal inflammatory reaction the uptake values of tumours from 90 min images were significantly higher than those from 45 min images, whereas the FDG accumulation of inflammatory lesions decreased over time. In 26 patients who had dual time FDG-PET scans the uptake values of delayed images from the known malignant lesions compared with those of earlier scans increased over time. By contrast, the FDG accumulation of benign lung nodules decreased slightly over time and FDG uptake in inflammatory lesions caused by radiation therapy and the lesions of painful lower limb prostheses remained stable over time. These findings are explained by the fact that most tumour cells have a low level of glucose-6-phosphatase and high levels of hexokinase activity. This may lead to a greater accumulation with time in tumours as opposed to normal tissues where dephosphorylation and cellular export of FDG may occur. Furthermore, the predominant glucose transporter in tumours is asymmetric favouring influx, the other isoforms are symmetric.
4. FDG-PET as an indicator of prognosis Mesothelioma may have a highly variable clinical course, with occasional long-term survivors. Prog-
S75
nostic information could be of value in determining whether to pursue an aggressive therapeutic approach. Therefore, the value of FDG-PET as an indicator of prognosis was examined in 17 patients [9]. The survival distribution in the group with high FDG uptake showed significantly shorter survival as compared with the low FDG uptake group indicating that patients with highly active mesotheliomas on FDG-PET imaging have a poor prognosis. PET allows quantitation of the metabolic state of malignant lesions. Therefore, the comparison of the values prior to and after therapy may be used for the early assessment of therapeutic efficacy. Positron emission tomography using tracers of tumour metabolism has been applied for the evaluation of treatment response during chemotherapy, gene therapy, and radiotherapy in a variety of tumours, indicating that these tracers deliver useful parameters for the early assessment of therapeutic efficacy [10—12]. Only very small numbers of patients with mesothelioma have been studied. In these patients a decreased tracer uptake was observed after chemotherapy [5].
5. Conclusion In conclusion, definitive statements of the value of FDG-PET for the diagnosis of mesothelioma are not possible due to the limited number of studies available. However, in difficult cases where conventional imaging cannot clearly establish whether a pleural lesion is malignant, PET may be helpful in deciding whether to pursue the investigation with thoracoscopy or thoracotomy [2]. PET imaging frequently demonstrated more extensive disease involvement than that revealed by other imaging modalities and in some cases even more than documented with thoracoscopy [2]. Therefore, PET may be useful in the staging procedure to identify malignant nodal involvement or distant metastases from pleural mesothelioma [13]. Further possible applications include diagnosing recurrence after radical surgery or radiation therapy in the face of eqivocal CT scans and assessment of disease response to treatment.
References [1] Ho L, Sugarbaker DJ, Skarin AT. Malignant pleural mesothelioma. Cancer Treat Res 2001;105:327—73. [2] Benard F, Sterman D, Smith RJ, Kaiser LR, Albelda SM, Alavi A. Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography. Chest 1998;114:713—22.
S76 [3] Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, et al. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990;170:223—30. [4] Haberkorn U, Ziegler SI, Oberdorfer F, Trojan H, Haag D, Peschke P, et al. FDG uptake tumor proliferation and expression of glycolysis associated genes in animal tumor models. Nucl Med Biol 1994;21:827—34. [5] Carretta A, Landoni C, Melloni G, Ceresoli GL, Compierchio A, Fazio F, et al. 18-FDG positron emission tomography in the evaluation of malignant pleural diseases–—a pilot study. Eur J Cardiothorac Surg 2000;17:377—83. [6] Buchmann I, Guhlmann CA, Elsner K, Gfrorer W, Schirrmeister H, Kotzerke J, et al. F-18-FDG PET for primary diagnosis differential diagnosis of pleural processes. Nuklearmedizin 1999;38:319—22. [7] Schneider DB, Clary-Macy C, Challa S, Sasse KC, Merrick SH, Hawkins R, et al. Positron emission tomography with F-18-fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2000;120:128—33. [8] Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18 F-FDG PET imaging
U. Haberkorn
[9]
[10]
[11]
[12]
[13]
for differentiating malignant from inflammatory processes. J Nucl Med 2001;42:1412—7. Benard F, Sterman D, Smith RJ, Kaiser LR, Albelda SM, Alavi A. Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med 1999;40:1241— 5. Haberkorn U, Strauss LG, Dimitrakopoulou A, Seiffert E, Oberdorfer F, Ziegler S, et al. Fluorodeoxyglucose imaging of advanced head and neck cancer after chemotherapy. J Nucl Med 1993;34:12—7. Haberkorn U, Strauss LG, Dimitrakopoulou A, Engenhart R, Oberdorfer F, Ostertag H, et al. PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J Nucl Med 1991;32:1485—90. Haberkorn U, Bellemann ME, Gerlach L, Morr I, Trojan H, Brix G, et al. Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase. Gene Ther 1998;5:880— 7. Marom EM, Erasmus JJ, Pass HI, Patz Jr EF. The role of imaging in malignant pleural mesothelioma. Semin Oncol 2002;29:26—35.
Positron emission tomography in the diagnosis of mesothelioma Uwe Haberkorn* Department of Nuclear Medicine, University of Heidelberg, German Cancer Research Center, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany
KEYWORDS Malignant pleural mesothelioma; Diffuse pleural thickening; CT; MRI; FDG-PET imaging
Summary The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies and a need for new diagnostic techniques to identify the extent of the disease at an early stage and to evaluate treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in identifying the location and extent of the involved areas but cannot always differentiate between benign and malignant processes. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging, which in oncology, is based on changes in metabolic pathways of glucose, has been shown in a number of studies to differentiate malign and benign lesions in patients with asbestos exposure. FDG-PET images were also found to provide excellent delineation of the active tumour sites. Further evaluations of this technique included a combined experimental/clinical study to investigate the difference in rates of FDG uptake between malignant and inflammatory cells and processes. © 2004 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The diagnosis and therapy of mesothelioma is still challenging. Currently, the best chance for long-term survival is achieved with early diagnosis and aggressive surgery, but due to the long delay between the onset of symptoms and the diagnosis, this is only possible with an extensive diagnosic workup. Aggressive surgery is required for optimal debulking, and extrapleural pneumonectomy may offer better local control compared with pleurectomy/ecortication. Delivery of optimal radiation schedules, which may involve large fractions as well as large total doses, is limited by the presence of nearby dose-limiting structures. * Tel.: +49-6221-567-731; fax: +49-6221-565-473. E-mail address: uwe [email protected] (U. Haberkorn).
Current chemotherapy only rarely leads to objective responses and improved survival, although gemcitabine and interleukin-2 (IL-2) may be active agents to be combined with radiation and/or other agents. Many of these techniques may provide greater benefit when used in the setting of adjuvant protocols or minimal residual disease, emphasising the importance of multimodality therapy [1]. The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies, which still need to be fully validated. This results in a need for new diagnostic techniques that can lead to a definite diagnosis and to a satisfactory evaluation of the response to treatment. Therefore, imaging procedures need to deliver an evaluation of the extent of a lesion, differential diagnosis between malignant and benign lesions, accurate staging and monitoring of therapy response.
0169-5002/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2004.04.016
S74
2. Imaging techniques Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in identifying the location and extent of the involved areas. However, diffuse pleural thickening can represent either a benign or a malignant process, particularly in asbestos-exposed workers. Diffuse pleural thickening is not specific and may be caused by asbestos exposure, as a consequence of haemorrhagic effusion or by a number of infectious processes such as tuberculosis or empyema. Therefore, the sensitivity and specificity of CT to predict the malignant nature of diffuse pleural lesions are 72 and 83% (MRI 100 and 87%). Scintigraphy with 67 Gallium shows a sensitivity of 86% and a specificity of 81%, but suffers from low resolution [2]. The combination of fine needle pleural biopsy and fluid cytology shows only a sensitivity of <40%. CT-guided pleural needle biopsy reaches 60% for a single biopsy and 85% for repeated biopsies [2]. In contrast, thoracoscopy has a sensitivity of >90% with a low mortality rate (<0.1%) but nonfatal complications in up to 10% of the patients (tumour seeding along the chest wall, empyema, haemorrhage, subcutaneous emphysema, wound infection). The method remains the primary diagnostic modality for mesothelioma, but this invasive approach cannot always accurately stage the mediastinal nodes or transdiaphragmatic extension.
3. FDG-PET imaging Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in oncology is based on changes in metabolic pathways of glucose. For glucose metabolism, three key enzymes for glycolysis (glucokinase, phosphofructokinase, pyruvate kinase) and four key enzymes for gluconeogenesis (glucose6-phosphatase, fructose-1,6,-diphosphatase, phosphoenolpyruvate carboxykinase, pyruvate carboxylase) were identified. The velocity and direction of these opposite metabolic pathways are determined by the amount and the activity of these enzymes. In tumours, glycolytic enzymes are upregulated, whereas the gluconeogenetic enzymes are downregulated. These changes are coupled to the progression of tumour development. Furthermore, changes in the pattern of the isoenzymes with prevalence of non-specific isoforms and high affinity (low Km ) occur. Furthermore, the type 1 glucose transporter (GLUT1) gene is seen as one of the early genes, which are activated early after transformation of cells with oncogenes such as src,
U. Haberkorn ras or fps. Consequently, an increased amount of types 1 and 3 GLUT mRNA has been demonstrated in a variety of human tumour tissues [3]. PET measurements of FDG accumulation in different animal tumours showed a correlation of tracer FDG uptake and the mRNA content of GLUT1 as well as the hexokinase [4]. Possible applications of PET for imaging of mesothelioma are: to detect and stage the extent, to differentiate between malignant and benign lesions in patients with asbestos exposure who present with atypical diffuse pleural thickening or pleural effusion with a normal CT scan, assessment of disease progression, and evaluation of disease response to treatment. However, at present only a few studies with a limited number of patients have been performed. Carretta et al studied 14 patients (10 with malignant pleural mesothelioma, three with other malignant tumours and one with benign disease) with CT scan evidence of pleural thickening, or fluid [5]. PET assessment demonstrated significant 18 FDG uptake in 12/13 patients with a malignant disease, also revealing distant metastases in two of them (overall accuracy of 92%). A false-negative result was observed in a patient with an epithelial mesothelioma and a benign pleural disease without significant uptake was correctly diagnosed in another patient. A similar study by Buchmann et al. [6] in 16 patients (four with benign pleural changes) revealed that all 12 pleural or intrapulmonal malignant tumours had high FDG-uptake and were classified correctly. The four histologically benign lesions were correctly interpreted as nonmalignant due to their low FDG accumulation. Benard et al. [2] examined the value of FDG-PET for the differentiation between malignant versus benign lesions in 28 patients (24 with malignant disease). The uptake of FDG was significantly higher in malignant than in benign lesions. With a cut off value of 2.0 for FDG uptake to differentiate between malignant and benign disease, a sensitivity of 91% and a specificity of 100% could be achieved, although the activity in some epithelial mesotheliomas tended to be close to this threshold indicating that there is a potential overlap between mesothelioma with low FDG uptake and severe pleural inflammation. Also the limited number of patients with benign disease in this study precludes definitive statements. FDG-PET images provided excellent delineation of the active tumour sites. Hypermetabolic lymph node involvement was noted on FDG-PET images in 12 patients, nine of which appeared normal on CT scans. Histologic examination in six patients confirmed malignant nodal disease in five cases and indicated granulomatous lymphadenitis in one. In a study population of 18 pa-
Positron emission tomography in the diagnosis of mesothelioma tients two false-positive results were observed: increased FDG uptake in the contralateral chest that was negative by thoracoscopic biopsy and increased abdominal FDG uptake after partial colectomy for diverticular disease [7]. Identification of occult extrathoracic metastases by positron emission tomography was the basis for excluding two patients from surgical therapy [7]. Since mesotheliomas can involve very diffusely the parietal pleura with a thin layer of malignant cells partial volume effects may be a problem. The tumours represent irregular sheet-like lesions of uncertain thickness which makes a correction as done with spherical tumours more challenging. This may cause problems for the differential diagnosis of small lesions. A combined experimental/clinical study investigated the difference in the rates of FDG uptake between malignant and inflammatory cells and processes [8]. In vitro studies of the FDG uptake in different tumour cell lines (human mesothelioma; rat mesothelioma; mice melanoma; mice mesothelioma; human myeloma; and human ovarian cancer) and peripheral blood mononuclear cells isolated from eight healthy human volunteers revealed a significantly increased FDG uptake in most tumour cell lines over time, whereas the FDG uptake in mononuclear cells was decreased in seven of eight donors. In animal studies with rat mesothelioma and focal inflammatory reaction the uptake values of tumours from 90 min images were significantly higher than those from 45 min images, whereas the FDG accumulation of inflammatory lesions decreased over time. In 26 patients who had dual time FDG-PET scans the uptake values of delayed images from the known malignant lesions compared with those of earlier scans increased over time. By contrast, the FDG accumulation of benign lung nodules decreased slightly over time and FDG uptake in inflammatory lesions caused by radiation therapy and the lesions of painful lower limb prostheses remained stable over time. These findings are explained by the fact that most tumour cells have a low level of glucose-6-phosphatase and high levels of hexokinase activity. This may lead to a greater accumulation with time in tumours as opposed to normal tissues where dephosphorylation and cellular export of FDG may occur. Furthermore, the predominant glucose transporter in tumours is asymmetric favouring influx, the other isoforms are symmetric.
4. FDG-PET as an indicator of prognosis Mesothelioma may have a highly variable clinical course, with occasional long-term survivors. Prog-
S75
nostic information could be of value in determining whether to pursue an aggressive therapeutic approach. Therefore, the value of FDG-PET as an indicator of prognosis was examined in 17 patients [9]. The survival distribution in the group with high FDG uptake showed significantly shorter survival as compared with the low FDG uptake group indicating that patients with highly active mesotheliomas on FDG-PET imaging have a poor prognosis. PET allows quantitation of the metabolic state of malignant lesions. Therefore, the comparison of the values prior to and after therapy may be used for the early assessment of therapeutic efficacy. Positron emission tomography using tracers of tumour metabolism has been applied for the evaluation of treatment response during chemotherapy, gene therapy, and radiotherapy in a variety of tumours, indicating that these tracers deliver useful parameters for the early assessment of therapeutic efficacy [10—12]. Only very small numbers of patients with mesothelioma have been studied. In these patients a decreased tracer uptake was observed after chemotherapy [5].
5. Conclusion In conclusion, definitive statements of the value of FDG-PET for the diagnosis of mesothelioma are not possible due to the limited number of studies available. However, in difficult cases where conventional imaging cannot clearly establish whether a pleural lesion is malignant, PET may be helpful in deciding whether to pursue the investigation with thoracoscopy or thoracotomy [2]. PET imaging frequently demonstrated more extensive disease involvement than that revealed by other imaging modalities and in some cases even more than documented with thoracoscopy [2]. Therefore, PET may be useful in the staging procedure to identify malignant nodal involvement or distant metastases from pleural mesothelioma [13]. Further possible applications include diagnosing recurrence after radical surgery or radiation therapy in the face of eqivocal CT scans and assessment of disease response to treatment.
References [1] Ho L, Sugarbaker DJ, Skarin AT. Malignant pleural mesothelioma. Cancer Treat Res 2001;105:327—73. [2] Benard F, Sterman D, Smith RJ, Kaiser LR, Albelda SM, Alavi A. Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography. Chest 1998;114:713—22.
S76 [3] Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, et al. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990;170:223—30. [4] Haberkorn U, Ziegler SI, Oberdorfer F, Trojan H, Haag D, Peschke P, et al. FDG uptake tumor proliferation and expression of glycolysis associated genes in animal tumor models. Nucl Med Biol 1994;21:827—34. [5] Carretta A, Landoni C, Melloni G, Ceresoli GL, Compierchio A, Fazio F, et al. 18-FDG positron emission tomography in the evaluation of malignant pleural diseases–—a pilot study. Eur J Cardiothorac Surg 2000;17:377—83. [6] Buchmann I, Guhlmann CA, Elsner K, Gfrorer W, Schirrmeister H, Kotzerke J, et al. F-18-FDG PET for primary diagnosis differential diagnosis of pleural processes. Nuklearmedizin 1999;38:319—22. [7] Schneider DB, Clary-Macy C, Challa S, Sasse KC, Merrick SH, Hawkins R, et al. Positron emission tomography with F-18-fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2000;120:128—33. [8] Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18 F-FDG PET imaging
U. Haberkorn
[9]
[10]
[11]
[12]
[13]
for differentiating malignant from inflammatory processes. J Nucl Med 2001;42:1412—7. Benard F, Sterman D, Smith RJ, Kaiser LR, Albelda SM, Alavi A. Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med 1999;40:1241— 5. Haberkorn U, Strauss LG, Dimitrakopoulou A, Seiffert E, Oberdorfer F, Ziegler S, et al. Fluorodeoxyglucose imaging of advanced head and neck cancer after chemotherapy. J Nucl Med 1993;34:12—7. Haberkorn U, Strauss LG, Dimitrakopoulou A, Engenhart R, Oberdorfer F, Ostertag H, et al. PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J Nucl Med 1991;32:1485—90. Haberkorn U, Bellemann ME, Gerlach L, Morr I, Trojan H, Brix G, et al. Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase. Gene Ther 1998;5:880— 7. Marom EM, Erasmus JJ, Pass HI, Patz Jr EF. The role of imaging in malignant pleural mesothelioma. Semin Oncol 2002;29:26—35.