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The Oncologist, Vol. 2, No. 6, 381–388, December 1997
© 1997 AlphaMed Press

Positron Emission Tomography: Current Role for Diagnosis and Therapy Monitoring in Oncology

Ludwig G. Strauss

Deutsches Krebsforschungszentrum, German Cancer Research Center, Heidelberg, Germany

Correspondence: Ludwig G. Strauss, M.D., Deutsches Krebsforschungszentrum, German Cancer Research Center, Division of Oncological Diagnostics and Therapy, Medical PET Group - Biological Imaging, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany. Telephone: 49-6221-42-24-77; Fax: 49-6221-42-24-76; e-mail: l.strauss{at}dkfz-heidelberg.de


   ABSTRACT
Top
 Abstract
Introduction
 Technical Aspects
 Diagnostic Aspects
 Therapy Management
 Conclusions
 References
 
High-resolution cross-sectional imaging improved dramatically the diagnosis and therapy management of oncological patients, although several questions remained open, primarily concerning the exact initial staging, the differential diagnosis of recurrent tumors, and therapy management. Positron emission tomography (PET) is a quantitative, functional imaging modality from the field of nuclear medicine which has the potential to yield physiological information. The diagnosis of tumors with PET is based on the increased regional glucose metabolism. Furthermore, PET can serve as a valuable tool for monitoring therapeutic effects.

The most common tracer used for oncological studies is F-18-deoxyglucose (FDG), a glucose analog. FDG-PET has been evaluated in different tumor types such as colorectal cancer, malignant lymphomas, melanomas, soft-tissue sarcomas, and lung tumors for both the diagnosis of primary tumors and recurrent lesions. The sensitivity of PET-FDG studies exceeds 85%, dependent on tumor type, size, and location. The diagnosis of viable tumor tissue following chemotherapy is another application of PET. A limitation of FDG-PET studies is false positive results, e.g., due to inflammation. This problem may be overcome by the use of multitracer studies and/or labeled amino acids.

Different procedures can be used to evaluate therapeutic effects. FDG follow-up studies are used to assess early effects and to predict long-term response. Pharmacokinetic studies of labeled therapeutic agents such as F-18-fluorouracil or C-11-ethanol provide exclusively quantitative data about transport and elimination of a drug. PET with labeled cytostatic drugs permits a prognosis prior to onset of chemotherapy. This procedure is recommended for monochemotherapy. In patients receiving polychemotherapy, the evaluation of different resistance mechanisms is needed and new approaches using suitable substrates, e.g., for the P-glycoprotein, are being developed or are already in use for scientific purposes.

Key Words. Positron emission tomography • Diagnosis • Therapy • Management • FDG • Drugs


   INTRODUCTION
Top
 Abstract
 Introduction
Technical Aspects
 Diagnostic Aspects
 Therapy Management
 Conclusions
 References
 
One major improvement in the management of oncological patients was the routine use of cross-sectional imaging methods for both tumor diagnosis and therapy planning. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) provide morphological information about a mass. The information about location, size, and infiltration is important for an accurate assessment of tumors and metastases. However, less attention has been given to the development of noninvasive methods of quantifying functional parameters in patients. Nuclear medicine procedures are primarily suitable for evaluating functional data on the basis of radiolabeled compounds. Positron emission tomography (PET) is one technique that has the potential to yield the physiologic information necessary for the diagnosis of tumors based on increased regional metabolism, and also to serve as a valuable tool for monitoring chemotherapeutic effects and the early diagnosis of tumor recurrence [1].

PET studies of tumors can be performed to gain qualitative and quantitative data for several reasons:

{blacktriangleup}Quantification of tissue perfusion
{blacktriangleup}Evaluation of tumor metabolism
{blacktriangleup}Transport of amino acids
{blacktriangleup}Tracing of radiolabeled cytostatic agents

Nuclear medicine procedures demand the use of radioactive isotopes and labeling of pharmaceuticals. Different radio-pharmaceuticals were used for patient examinations (Table 1Go).


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  		Table 1. Radiopharmaceuticals for PET studies
 
One of the most commonly used tracers for oncological examinations is F-18-deoxyglucose (FDG), a glucose analog. FDG is transported and phosphorylated like glucose but then trapped in the cells. Due to the very slow dephosphorylation rate, PET imaging can be performed for a certain time interval to evaluate the regional metabolism.

The new PET scanners are based on a block detector design and provide an axial field of view (FOV) of at least 10 cm. Two PET systems, GE-Scanditronix PC-2048-7WB and Siemens ECAT HR+, which provide an axial FOV of 3.5 cm and 15.2 cm, respectively, are in use for patient studies at our institution. Up to 63 cross sections can be reconstructed from the dynamically acquired data. The most commonly used isotopes are O-15 (half life 2 min), C-11 (half life 20 min) and F-18 (half life 110 min). Perfusion measurements are routinely performed with H215O, which is an inert tracer with free distribution between blood and tissue. A dynamic study is performed after intravenous tracer injection, and data are acquired for up to 10 min. FDG is the most commonly used tracer for metabolic studies. Dynamic studies up to 60 min as well as static acquisitions more than 30 min following tracer application are performed. Whole-body acquisition protocols are used in some patients if larger areas must be examined. Radiolabeled cytostatic agents are limited to a small number of compounds. We use F-18-fluorouracil (F-18-FU) in patients with metastatic colorectal tumors to evaluate the flourouracil (FU) pharmacokinetics and to predict response to chemotherapy. Dynamic data acquisitions are performed up to 120 min following a short 12-min F-18-FU infusion. Cross sections can be reconstructed using the standard filtered backprojection method implemented in the system or, as in most of the patients, using a new iterative reconstruction technique based on the work of Kontaxakis et al. [2]. The quantitative evaluation is performed with a region-of-interest (ROI) technique, and standardized uptake values (SUV) are calculated according to [1]:

The SUV is a distribution parameter reflecting the accumulation of a radiopharmaceutical in tissues. A value of 1.0 SUV represents a homogenous distribution, while values exceeding one reflect enhanced tracer uptake in the tissue. In selected cases, parametric images of the transport and influx of radiopharmaceuticals are calculated to support the evaluation of PET studies.


   TECHNICAL ASPECTS
Top
 Abstract
 Introduction
 Technical Aspects
Diagnostic Aspects
 Therapy Management
 Conclusions
 References
 
Whole-body studies are generally helpful for the initial evaluation of patients and to detect unknown malignant lesions. However, the whole-body technique is limited to the qualitative assessment of the images, because transmission data are not acquired and the emission data cannot provide reconstructed cross sections with acceptable image quality. This can raise problems for therapy follow-up studies as well as for the differentiation between residual tumor tissue and scar tissue due to the lack of quantitative data. Therefore, in most of the patients, we perform transmission measurements prior to the dynamic and/or static acquisition of emission data. Another important parameter for lesion detectability is the applied image reconstruction algorithm. The standard filtered backprojection method is limited by noise in low-count rate studies as well as sever artifacts if localized high tracer concentrations are present in the target area (e.g., kidney, bladder). We found a significant improvement in the image quality when the iterative method was used for the reconstruction [2] (Fig. 1Go).



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  		Figure 1. Soft tissue sarcoma of the right leg with increased FDG metabolism in the peripheral area and necrotic tissue in the central part (reference: surgery and histology). Standard filtered backprojection (left) and iterative image reconstruction (right). The iteratively reconstructed cross section provides a higher image quality as compared to the standard method.

 

   DIAGNOSTIC ASPECTS
Top
 Abstract
 Introduction
 Technical Aspects
 Diagnostic Aspects
Therapy Management
 Conclusions
 References
 
One major problem in oncological patients is accurate initial staging. While morphological methods such as CT and MRI are commonly used to achieve a classification according to the TNM system, PET can help to improve the staging accuracy by limiting the number of false negative results. The use of PET in patients with brain tumors was one of the first applications of this method. FDG can help to differentiate low-grade from high-grade brain tumors, as shown by Delbeke et al. [3]. The sensitivity and specificity were 94% and 77%, respectively, when a tumor-to-white-matter ratio of 1.5 was chosen. Due to the low FDG accumulation in low-grade lesions, multitracer PET studies with radiolabeled amino acids such as C-11-methionine [4] or C-11-tyrosine [5] can be useful for the improvement of the detectability of low-grade brain tumors.

Following the application in brain tumors, PET found increasing interest for studies of malignancies in the whole-body area (Fig. 2Go). It is known from the results of several groups that compared the staging of bronchogenic carcinoma with CT or MRI with the histological results that morphologic methods provide a sensitivity of 25%-71% for lymph node metastases and 52%-80% for the accurate description of the primary tumor [6-7]. We evaluated the tumor staging with CT alone and CT+PET in 20 patients with malignant lung tumors, and compared the T-classification with the surgical results. In 8 of 20 patients, a correct change of the T-staging was initiated based on the PET results [1]. Lewis et al. evaluated 34 patients with non-small cell lung cancer preoperatively and found a change in therapy management in 41% of the patients [8]. Wahl et al. noted an improvement of both sensitivity and specificity when the staging was compared in 23 patients with non-small cell carcinomas [9].



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  		Figure 2. Whole-body PET FDG study demonstrating multiple lymph node metastases (right neck, left clavicular region, left thoracic wall) in a patient with an adenocarcinoma.

 
The whole-body data acquisition is a common procedure for viewing tumorous lesions in the whole-body area, which is helpful for the initial staging of malignant lymphomas. Bangerter et al. evaluated the PET data in 58 patients with malignant lymphomas and found a sensitivity of 98% and specificity of 95% [10]. Comparable data are reported for malignant melanomas [11], colorectal carcinomas [12], head and neck tumors [13], sarcomas [14], breast carcinomas [15], and pancreatic carcinomas [16]. Furthermore, PET with FDG can be helpful for the classification of solitary lesions, as demonstrated by Dewan et al., for pulmonary nodules [17]. Eli et al. noted in malignant melanomas a higher FDG uptake for metastases from nodular melanomas (median value for 54 lesions: 4.63 SUV) than metastases from superficial-spreading malignant melanomas (median value for 119 lesions: 2.24 SUV) [18].

The sensitivity and specificity of FDG-PET depends, among other factors, on the lesion location [19, 20]. According to our data, PET with FDG was of limited value for the differentiation of unknown masses of the kidney due to the high-normal tracer accumulation in the renal parenchyma. The differentiation of small ovarian tumors can be difficult due to the FDG uptake in normal structures within the target area. Furthermore, highly differentiated hepatocellular carcinomas cannot be delineated from the normal liver parenchyma due to a liver-equivalent FDG uptake. Increased tracer uptake in normal structures may raise problems, e.g., in the diagnosis of prostatic cancer [21]. The differentiation of small lesions, e.g., involved normal-sized lymph node metastases located in metabolically active tissue, can also raise problems [22]. Submandibular lymph node metastases cannot always be delineated due to the normal FDG uptake noted in the glands. According to our data in lymphoma patients, the diagnosis of normal-sized mediastinal lymph node metastases is no major problem since 90% of the involved lesions demonstrated a higher FDG uptake than the background activity in the mediastinal vessels [23].

Another limitation of the PET FDG studies is the differentiation between inflammation and viable tumor tissue [24-26]. It is known that acute inflammatory processes demonstrate a comparable high FDG uptake and cannot be differentiated from viable tumor tissue [27-28]. Experimental studies with FDG and H-3-deoxyglucose in tumor-bearing mice using the microautoradiographic technique demonstrated that 29% of the measured FDG uptake in a tumor lesion is due to inflammatory or other benign elements such as granulation tissue and macrophages. According to our preliminary data using multi-tracer PET studies in patients with inflammatory masses, liver tumors, colorectal tumors, soft-tissue sarcomas and lymphoma recurrences, a specific marker of the A-type amino acid transport, the C-11-aminoisobutyric acid (C-11-AIB), did not show any accumulation in the inflammatory lesions. In contrast, an increased AIB uptake was noted for the soft-tissue sarcomas and the colorrectal tumors but not for the Hodgkin’s and the non-Hodgkin’s recurrences. A combination of C-11-AIB with F-18-FDG may help differentiate inflammatory lesions from viable tumor tissue. However, more data are needed to evaluate the multitracer approach for clinical use.


   THERAPY MANAGEMENT
Top
 Abstract
 Introduction
 Technical Aspects
 Diagnostic Aspects
 Therapy Management
Conclusions
 References
 
Diagnosis of Viable Tissue Following Treatment
The differentiation of benign structures from residual or recurrent tumor tissue can be significantly improved by the application of metabolically active tracers (Fig 2Go). Kahn et al. compared the diagnosis of recurrent brain tumors with TI-201 single-photon emission tomography (SPECT) and FDG PET in 19 patients and noted a sensitivity of 69% for SPECT and 81% for PET when lesions greater than 1.6 cm were studied [19]. According to our results, PET with FDG should find preferential use in these patients due to the improved detection of small lesions and the ability to quantify the tumor metabolism.

One of the most common tumors in the whole-body area is colorectal carcinoma. Follow-up studies with CT have shown that the early detection of tumor recurrence is a major problem in the treatment of these patients. Therefore, FDG was used for the differentiation of recurrent tumor and scar tissue [20]. The results obtained in 30 patients with a recurrent tumor and 13 patients with scar tissue demonstrated both a high sensitivity (true positive: 29/30 patients) and specificity (true negative: 13/13 patients). The mean SUV 60 min after FDG application for the recurrent tumors was more than twice as high as in normal soft tissue. Beets et al. used the whole-body technique in 35 patients with metastatic colorectal cancer and found that the treatment management was affected in 14/35 patients [21].

The diagnosis of viable tumor tissue after first-line chemotherapy was investigated in patients with Hodgkin’s (HL) or non-Hodgkin’s lymphomas (NHL) [22-23]. Since approximately 30% of these patients are likely to have a relapse, PET can help to identify non-responders to support early second-line chemotherapy. Dimitrakopoulou-Strauss et al. evaluated 114 lesions in 46 patients with recurrent malignant lymphomas and noted that PET was able to detect more than 90% of all tumor lesions [22]. The second-line treatment is based on high-dose chemotherapy, followed by blood stem cell support if a patient fulfills the response criteria. The treatment was changed on the basis of the PET results in four of the 46 patients due to the presence of scar tissue or inflammatory lesions [22]. Therefore, a decrease in life quality for the patients was avoided and treatment costs were saved (more than $60,000 total cost for the treatment of each patient).

The PET FDG method can be used in a variety of other tumors to detect recurrent malignancies. The sensitivity and specificity exceeds 90% in most of the studies. Patz et al. quantified the FDG accumulation, were able to detect recurrent bronchogenic carcinomas, and could differentiate them from fibrosis [24]. Comparable data are reported from Garcia et al., who evaluated recurrent musculoskeletal sarcomas and found a sensitivity of 98% and specificity of 90% [25]. Recurrent head and neck tumors were evaluated by Lapela et al. [26]. The data obtained in 15 patients yielded a lower sensitivity of 88% and specificity of 86%. According to our experience, the data for sensitivity and specificity are dependent on several parameters, such as tumor type, tumor location, inflammatory reactions, previous treatment, and nonspecific treatment effects. Romahn et al. evaluated the FDG uptake prior, during and after radiation therapy in 14 patients with colorectal carcinoma, and found a false positive rate in 7/14 [27]. PET was found not to be helpful for the detection of viable tumor tissue within six months after commencement of radiotherapy [28]. In contrast, no major problems exist for the detection of viable tumor tissue in most of the patients undergoing chemotherapeutic treatment.

Evaluation of Treatment Effects

Early Therapeutic Effects During Chemotherapy
The PET protocols used for the evaluation of treatment effects are mainly dependent on the chemotherapeutic treatment protocol used in the individual patient. In some tumor types, early PET follow-up studies within the first chemotherapeutic treatment may be helpful for individual treatment planning. It was possible to demonstrate changes in FDG metabolism within two days following fotemustine therapy in patients with malignant melanomas[29]. Similar results were obtained for the combined treatment protocols with dacarbazine/alpha-interferon (Fig. 3Go). However, PET follow-up studies with larger patient collectives are required to establish the use of PET with FDG for the evaluation of early therapeutic effects.



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  		Figure 3. Follow-up examinations in a patient with metastasis from a malignant melanoma. PET with FDG was performed prior to chemotherapy, one day after decarbazine treatment and in the follow-up period after alpha-interferon treatment. A uniform increase in regional metabolism was observed, suggesting non-response to treatment. The prediction of response based on the early PET follow-up data was confirmed by volumetric data for the metastasis obtained from CT follow-up studies.

 

Evaluation of Chemotherapy Within One to Three Treatment Cycles
One standard approach is the quantification of tumor metabolism prior to the first and immediately prior to the second chemotherapeutic cycle. This protocol was evaluated in patients with head and neck tumors [30-31]. The change in FDG uptake was highly correlated for both primary tumors (r = 0.98) and lymph node metastases (r = 0.94). Furthermore, a higher FDG accumulation prior to chemotherapy was associated with a higher decrease in tumor volume. This was not observed in other tumors, such as malignant melanomas and lymphomas [18]. Wahl et al. evaluated the change in regional tumor metabolism in patients with breast cancers during the first three cycles of chemotherapeutic treatment and noted a rapid decrease in tumor metabolism after effective treatment, with the reduction of FDG accumulation antedating the decrement in tumor size [32]. Non-responding patients showed no significant decrease in FDG uptake as measured by SUV after the end of three cycles of treatment. Our data obtained in several different tumor types (lymphomas, head and neck tumors, melanomas, lung tumors) gave evidence that PET FDG studies prior to and within at least three chemotherapeutic cycles are likely to identify those patients who will not respond to treatment. In contrast to the continuous increase of the metabolism, a decrease in tumor metabolism may only be intermediate and is not a reliable parameter for a complete response to treatment. Comparable findings are reported by Tilgen et al. for melanomas [29].

While a decrease or increase of regional tumor metabolism can be associated with response or non-response to therapy, respectively, we noted a third pattern in some patients with small-cell lung carcinomas [1]. An intermediate decrease of tumor volume was associated with an unchanged tumor metabolism during chemotherapeutic treatment, followed later on by a final progression of the tumor volume. It is well known that tumor parenchyma can consist of non-resistant and resistant tumor fractions. When chemotherapy is initiated, the total tumor volume may decrease due to the therapeutic effect on the non-resistant part of the tumor. However, later on a progression is noted due to the increase in the number of resistant tumor cells. Therefore, a decrease in tumor volume with unchanged tumor metabolism may indicate the presence of resistance to the chemotherapeutic agents used for treatment.

Prediction of Long-Term Response
While short-term therapeutic effects can be assessed with PET and FDG, it is a difficult task to predict long-term therapeutic outcome on the basis of PET follow-up studies. It was shown that the calculation of the standard integral uptake

is correlated with therapy outcome [22]. The authors were able to predict complete response, stable disease, and progressive disease based on SIU and the use of at least three PET FDG follow-up studies prior to and during treatment [22]. Further studies in other tumors are planned to validate this procedure.

Evaluation of Radiation Therapy
Experimental studies have shown that radiation therapy activates several repair systems. Upon exposure to radiation treatment, cells can be damaged either by direct or indirect effects, which results in DNA damage. Some of the biochemical pathways involved in the repair of the radiation damage are known to be energy-dependent. Therefore, the accumulation of FDG can be enhanced following radiotherapy. PET FDG studies in patients with colorectal recurrences receiving radiation therapy demonstrated that the FDG uptake may be increased up to several months following treatment [27]. While the tumor metabolism is likely to decrease continuously during radiation therapy, FDG accumulation increases with time due to secondary reactions. At the moment, FDG PET can be used in selected cases if a therapeutic alternative is discussed after completion of radiation therapy [28].

Pharmacokinetics of Radiolabeled Drugs
While the evaluation of treatment effects requires at least two PET studies of the tumor metabolism, only one study with a radiolabeled drug is needed to evaluate the possible effect of the chemotherapeutic agent in the target area. However, labeling of cytostatic drugs is generally more difficult than labeling of metabolically active tracers. Therefore, only limited data exist about PET and radiolabeled drugs [33-34]. Ginos et al. evaluated the distribution of N-13-cisplatinum in brain tumors [33]. However, the short half life of N-13-cisplatinum (t1/2 = 10 min) limits tracer retention studies. Furthermore, it is still unknown if the label remains on the cytostatic drug during the PET examination. Diksic used C-11 labeling and studied the distribution of BCNU and SarCNU in brain tumors following regional drug application [34]. The most extensive patient studies were preformed with F-18-FU. Dimitrakopoulou et al. evaluated the regional pharmacokinetics of F-18-FU in 78 metastases following a short intravenous infusion of the tracer and nonlabeled FU [35]. The accumulation of the cytostatic drug was low in metastases, and about one-third of the concentration measured in the normal liver parenchyma. The F-18-FU uptake in the liver metastases is associated with therapy outcome [36, 37]. Therefore, PET studies with F-18-FU prior to initiation of chemotherapy can be used to predict therapy outcome. Furthermore, the advantage of modulated treatment protocols can be compared on the basis of F-18-FU uptake measurements to optimize the individual treatment protocol.

Besides F-18-FU, C-11-ethanol was used to evaluate the effect of the intratumoral therapy in patients with hepatocellular carcinomas [38]. The radiolabeled ethanol was administered together with non-labeled ethanol via a puncture needle positioned under sonographic guidance. A dynamic PET study was acquired, beginning with the application of the tracer. The data show that PET can provide information about the distribution and retention of the therapeutic drug (Fig 4Go). The data evaluation using spectral analysis showed a heterogeneous distribution of the ethanol in the tumor area without a significant washout. An elimination of the agent can be detected with PET even shortly after the tracer application, and therapy may be changed in the individual patient.



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  		Figure 4. Patient with hepatocellular carcinoma in the right liver lobe. Upper left: CT cross section; the tumor is poorly delineated. Upper middle: PET image after O-15-water application. Enhanced tissue perfusion of the tumor as compared to the normal liver parenchyma. Upper right: PET image after C-11-aminoisobutyric acid application. The a-type amino acid transport is decreased in the tumor. Lower left: PET FDG image prior to therapy. Enhanced regional metabolism in the tumor. Lower middle: PET C-11-ethanol image shortly after the intratumoral application of the therapeutic dose of ethanol and the tracer dose. The drug remains in the target area, no leakage is observed. Lower right: PET FDG follow-up study two weeks after treatment. Decreased metabolism in the tumor, indicating a sufficient treatment effect.

 

   CONCLUSIONS
Top
 Abstract
 Introduction
 Technical Aspects
 Diagnostic Aspects
 Therapy Management
 Conclusions
References
 
Metabolic PET studies, which are performed with FDG at most institutions, are gaining increasing importance for both initial tumor staging and the detection of tumor recurrence. However, we feel that PET should find preferential use as a second-line method when morphological procedures are inconclusive and a therapeutic decision cannot be made with the required accuracy on the basis of the morphological procedures alone. Within these limits, PET can improve the T- and N-staging of tumors. The detection of residual tumor tissue is important, e.g., for malignant lymphomas to direct the patients to a second-line treatment in an early phase. PET studies with FDG help to identify recurrent tumor tissue with a high diagnostic accuracy, e.g., in colorectal tumors, sarcomas and lung tumors. Studies with radiolabeled cytostatic agents such as F-18-FU and other tracers are limited to some centers due to the availability of these compounds. F-18-FU can be used in the individual patient when data about the possible response to treatment are required for therapy management. PET studies for the evaluation of different resistance mechanisms, such as multidrug resistance using suitable substrates labeled with a positron emitter, are planned for the near future for further optimization of therapy monitoring with PET.


   REFERENCES
Top
 Abstract
 Introduction
 Technical Aspects
 Diagnostic Aspects
 Therapy Management
 Conclusions
 References
 

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  33. Ginos JZ, Cooper AJL, Dhawan V et al. [13N]cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors. J Nucl Med 1987;28:1844–1852.[Abstract/Free Full Text]
  34. Diksic MA, Mitsuka S, Conway T et al. Use of PET to evaluate in vivo pharmacokinetics of chemotherapeutic agents. BCNU and SarCNU in humans. Tumor Diagnostik & Therapie 1988;9:171.
  35. Dimitrakopoulou A, Strauss LG, Clorius JH et al. Studies with positron emission tomography after systemic administration of fluorine-18-uracil in patients with liver metastases from colorectal carcinoma. J Nucl Med 1982;34:1075–1081.[Abstract/Free Full Text]
  36. Strauss LG. Application of positron emission tomography in colorectal carcinoma. Onkologie 1993;16:232–244.
  37. Dimitrakopoulou-Strauss A. New approaches for noninvasive quantification of chemotherapeutic drugs in tumors and the evaluation of multidrug resistance. The Cancer Journal 1996;9:118–120.
  38. Dimitrakopoulou-Strauss A, Gutzler F, Strauss LG et al. PET-Studien mit C-11-Äthanol bei der intratumoralen Therapie von hepatozellulären Karzinomen. Radiologe 1996;36:744–759.[Medline]
accepted for publication July 30, 1997.




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