Chest Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (26)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hara, T.
Right arrow Articles by Niino, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hara, T.
Right arrow Articles by Niino, H.
(Chest. 2003;124:893-901.)
© 2003 American College of Chest Physicians

Uptake Rates of 18F-Fluorodeoxyglucose and 11C-Choline in Lung Cancer and Pulmonary Tuberculosis*

A Positron Emission Tomography Study

Toshihiko Hara, MD, PhD; Noboru Kosaka, MD; Tsuneo Suzuki, MD; Koichiro Kudo, MD and Hitoshi Niino, MD, PhD

* From the Departments of Radiology (Drs. Hara and Kosaka), Internal Medicine (Drs. Suzuki and Kudo), and Pathology (Dr. Niino), International Medical Center of Japan, Tokyo, Japan.

Correspondence to: Toshihiko Hara, MD, PhD, Department of Radiology, Indiana University School of Medicine, 1345 West 16th St, L-3, Room 212, Indianapolis, IN 46202-2111; e-mail: toshara{at}iupui.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Study objective: The purpose of this study was to examine the uptake rates of 18F-fluorodeoxyglucose (FDG) and 11C-choline in patients with lung cancer, pulmonary tuberculosis, and atypical mycobacterial infection of the lung by positron emission tomography (PET) scanning with relation to their tumor size.

Design: Ninety-seven patients with untreated lung cancer, 14 patients with untreated pulmonary tuberculosis, and 5 patients with untreated atypical mycobacterial infection were examined. The diagnosis of lung cancer was confirmed pathologically after biopsy and surgery. The diagnosis of tuberculosis and atypical mycobacterial infection was confirmed by bacterial culture. The uptake rates of FDG and 11C-choline were presented quantitatively as the standardized uptake value (SUV).

Setting: International Medical Center of Japan.

Results: In lung cancer patients, the SUV of FDG increased with increasing tumor size, whereas the SUV of 11C-choline was almost constant at around 3.5 for every tumor size. In tuberculosis patients, the SUV of FDG increased with increasing tumor size, whereas the SUV of 11C-choline was almost constant at around 2 for every tumor size. In atypical mycobacterial infection patients, the SUV of FDG and the SUV of 11C-choline were equally low at around <= 2.

Conclusion: The differences in the SUVs of FDG and 11C-choline in patients with lung cancer, tuberculosis, and atypical mycobacterial infection for the same tumor size (tumor size, > 1.5 cm) were distinct. In lung cancer patients, the SUVs of both FDG and 11C-choline were high. In tuberculosis patients, the SUV of FDG was high, but the SUV of 11C-choline was low. In atypical mycobacterial infection patients, the SUVs of both FDG and 11C-choline were low. It may be possible to apply this principle to make a presumptive diagnosis of a solitary pulmonary nodule if it is too small to make a definitive diagnosis pathologically and bacteriologically.

Key Words: atypical mycobacterial infection of the lung • choline • differential diagnosis • fluorodeoxyglucose • lung cancer • positron emission tomography • pulmonary tuberculosis • solitary pulmonary nodules


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Solitary pulmonary nodules (SPNs) are commonly encountered in clinical practice. In the United States, > 80% of SPN cases are either lung cancer or granulomas, and the proportion of their occurrence is equal.1 2 In Japan, lung granulomas arise mostly from tuberculosis or atypical mycobacterial infection, although they are either active (ie, culture-positive) or inactive (ie, culture-negative).3 Differentiating lung cancers from benign lesions, including active tuberculosis, is very important, because the treatments for them are so different.

Positron emission tomography (PET) is able to image the metabolic differences between normal and malignant cells using tumor-seeking tracers. 18F-fluorodeoxyglucose (FDG) is the most established tracer of this kind.4 Malik et al5 compared histologic findings and the result of FDG-PET scans in 36 patients with indeterminate SPNs. Of 24 lung-cancer patients, 21 had true-positive findings. Of 12 non-lung cancer patients, 1 patient with active tuberculosis had a false-positive finding for lung cancer, and 11 other patients, mostly with inactive granuloma, had true-negative findings for lung cancer. The findings of their present study clearly showed that FDG-PET scanning was very accurate for the diagnosis of lung cancer, with only the drawback of giving a false-positive result for patients with active tuberculosis. A number of other studies6 7 8 9 10 11 also have suggested the difficulty of distinguishing patients with lung cancer from those with pulmonary tuberculosis using FDG.

11C-choline is another tracer that has been used for imaging malignancies. 11C-choline PET scanning is more sensitive than FDG-PET scanning in detecting lung cancer and mediastinal lymph node metastasis, when the tumor size is very small.12 The uptake of FDG and 11C-choline in tumors can be normalized by correcting differences in the total injected dose and body weight. The normalized uptake rate in terms of radioactivity concentration is called the standardized uptake value (SUV), where

.

Empirically, we noticed the following phenomena.13 In lung cancer patients, (1) the SUV of FDG was very high in large tumors but very low in small tumors, and (2) the SUV of 11C-choline was almost constant in every tumor size. In contrast, in pulmonary tuberculosis patients, (1) the SUV of FDG was very high for every tumor size, and (2) the SUV of 11C-choline was very low for every tumor size. In short, the FDG and 11C-choline uptake patterns in lung cancer patients were very different from those in pulmonary tuberculosis patients. These differences may have a practical utility, because, once this principle is established, it will be applicable to the differential diagnosis of SPNs. Thus, we sought to establish this principle in the study of a large number of patients.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 References
 
Patients
Ninety-seven untreated patients with lung cancer (74 men and 23 women; age range, 49 to 86 years; mean [± SD] age, 66.1 ± 9.3 years) and 19 untreated patients with mycobacterial infection of the lung (15 men and 4 women; age range, 26 to 84 years; mean age, 51.9 ± 15.5 years) were registered in this study. The histologic types of lung cancer were as follows: adenocarcinoma, 49 patients; squamous cell carcinoma, 31 patients; small-cell carcinoma, 8 patients; large-cell carcinoma, 7 patients; and bronchioloalveolar carcinoma, 2 patients. The Mycobacterium species found were as follows: Mycobacterium tuberculosis, 14 patients; and atypical mycobacteria, 5 patients. The diagnosis of lung cancer was confirmed pathologically in specimens obtained at biopsy and surgery. The diagnosis of mycobacterial infection was confirmed by culture of the bacteria (ie, culture-positive) in sputa, endoscopic specimens, or surgically resected specimens. The patients without pathologic and bacteriologic confirmations of disease were excluded from the statistical analyses.

In advance of this study, informed consent was obtained from the patients, and the investigational protocol was approved by the institutional review board.

PET Scan and Data Analysis
FDG (18F half-life, 110 min) and 11C-choline (half-life, 20 min) were prepared using a cyclotron and automated synthetic apparatuses that we constructed.10 PET scanning was performed in the morning after the patient had fasted overnight. The PET camera (Headtome IV with 6-mm spatial resolution; Shimadzu; Kyoto, Japan) was equipped with three rings of bismuth- germanate detectors to produce five slices at 13-mm intervals. FDG PET scans and 11C-choline PET scans were performed as follows. After the transmission scan was over, a bolus of FDG (370 mBq) or 11C-choline (370 mBq) was injected IV (using an IV catheter), followed by an infusion of a large volume of saline solution using the same IV line. The emission scan started 40 min after the injection of FDG or 5 min after the injection of 11C-choline. Both the transmission and emission scans were performed from the level of the liver to the level of the neck, by shifting the bed position six times, with a scan time of 3 min each. By combining the transmission and emission data in a computer, attenuation-corrected emission images (ie, PET images) were obtained. A series of horizontal images were displayed on a computer screen. The PET images were displayed in a color scale (or in a gray scale) that represented the SUV of each pixel (4 x 4 x 9.5 mm in real size). The computer also displayed the average SUV of the pixels enclosed within a region of interest (ROI) numerically.

In each patient, the major axis of the pulmonary lesion was measured on the CT image. Then, on the PET computer screen, an ROI (usually containing about 10 pixels) was selected, and the average SUV of the ROI was determined numerically.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 References
 
Typical PET Images of Lung Cancer and Pulmonary Tuberculosis
Figure 1 shows typical PET images of lung cancer and pulmonary tuberculosis that were obtained with FDG and 11C-choline. Primary lung cancer was visualized equally by FDG and 11C-choline. However, the metastatic lymph nodes in the mediastinum were better visualized by 11C-choline than by FDG. Pulmonary tuberculosis was strongly visualized by FDG but was only weakly visualized by 11C-choline.



View larger version (77K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1.. CT scan, FDG-PET scan, and 11C-choline-PET scan images of lung cancer and pulmonary tuberculosis (the deep-black color in the PET scan images represents an SUV of >= 4). The diagnosis was confirmed by pathologic and bacteriologic examinations. Primary lung cancer was visualized by both FDG and 11C-choline (one arrow each). The metastatic lymph nodes in the mediastinum were clearly visualized by 11C-choline (two arrows) but were faintly visualized by FDG (one arrow). In contrast, tuberculosis was clearly visualized by FDG (six arrows) but was faintly visualized by 11C-choline. The high SUV of FDG in the myocardium (in the image of lung cancer) was caused by hyperglycemia. Choline = 11C-choline.

 
Relationship Between SUV and Tumor Size in Lung Cancer
Figure 2 shows the relationship between the SUV and tumor size in patients with primary lung cancer (not including metastatic lymph nodes), using both with FDG and 11C-choline. If the tumor size increased, the SUV of FDG increased (Y = 0.916X; r = 0.510 [where Y is the SUV of FDG and X is tumor size]). In contrast, the SUV of 11C-choline was almost constant at around 3.5 (mean [± SD], 3.53 ± 1.23) for every tumor size. The tumors were mostly adenocarcinomas (49 tumors) and squamous cell carcinomas (31 tumors), and there was no significant difference in the SUV of FDG and 11C-choline between these tumor types. When other tumor types were examined, there were eight cases of small cell carcinoma with tumor sizes of 1.3, 1.6, 1.7, 2.5, 2.9, 3.1, 3.8, and 7.0 cm in which the SUVs of FDG were 2.88, 2.95, 2.19, 7.71, 1.86, 4.85, 6.99, and 6.75, respectively, and the SUVs of 11C-choline were 2.99, 2.61, 3.20, 6.22, 2.37, 2.08, 4.82, and 4.96, respectively. There were also two cases of bronchioloalveolar carcinoma with tumor sizes of 2.8 and 7.4 cm in which the SUVs of FDG were 4.16 and 2.10, respectively, and the SUVs of 11C-choline were 4.16 and 3.64, respectively. Although there was no significant difference in the SUVs of FDG and 11C-choline among all the tumor types named above, a single exception was found in one case of bronchioloalveolar carcinoma (tumor size, 7.4 cm) in which the SUV of FDG was very low (2.10), but the SUV of 11C-choline was normal (3.64).



View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2.. Relationship between tumor size and SUV in patients with primary lung cancer, with FDG and with 11C-choline. The larger the tumor size, the higher the SUV of FDG. The SUV of 11C-choline was almost constant at around 3.5 in every tumor size.

 
Relationship Between Tumor Size and SUV in Pulmonary Tuberculosis and Atypical Mycobacterial Infection of the Lung
Figure 3 shows the relationship between tumor size and SUV in 14 cases of pulmonary tuberculosis and 5 cases of atypical mycobacterial infection of the lung, using both FDG and 11C-choline. In patients with pulmonary tuberculosis, the larger the mass size, the higher the SUV of FDG (Y = 0.405X; r = 0.804). However, the SUV of 11C-choline in tuberculosis patients was almost constant at around 2 (mean, 2.08 ± 0.58), which constituted about half the SUV of 11C-choline observed in lung cancer. The pattern of atypical mycobacterial infection was completely different from the pattern of tuberculosis in that the SUVs of FDG and 11C-choline in patients with atypical mycobacterial infection were equally low. There was an exception in patients with atypical mycobacterial infection, in whom the SUV of FDG was very high (5.63), but the SUV of 11C-choline was low (2.00), resembling the pattern of tuberculosis. The CT scan of this case showed multiple lung abscesses unilaterally. The causative agent was Mycobacterium kansasii. The sputum was purulent with abundant polymorphonuclear leukocytes.



View larger version (13K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3.. Relationship between tumor size and SUV in patients with tuberculosis and atypical mycobacterial infection using FDG and 11C-choline. In tuberculosis patients, the larger the tumor size, the higher the SUV of FDG, and the SUV of 11C-choline was almost constant (approximately 2) for every tumor size. In atypical mycobacterial infection (Atyp mycobac), the SUVs of FDG and 11C-choline were equally low.

 
Decline of SUV of FDG and SUV of 11C-Choline in Small SPNs
The small nodules (ie, SPNs) always showed lower SUVs with FDG and 11C-choline than did the larger ones. The reason for the decline in SUVs appeared to be attributable to the following reasons: (1) the insufficient spatial resolution of the PET machine (6 mm with FDG and 11C-choline); and (2) the histologic differences in the vascular networks that distinguish small SPNs from large (only with FDG), as will be described in detail in the "Discussion" section. The tumor size that avoided the effect of insufficient spatial resolution was, experimentally and theoretically, 1.5 cm.14

Difference in the SUV Pattern Among Patients With Lung Cancer, Tuberculosis, and Atypical Mycobacterial Infection With Relatively Large Masses
When lung cancer, tuberculosis, and atypical mycobacterial infection were compared in a relatively large mass (ie, > 1.5 cm), the SUV patterns were clearly different. In lung cancer patients, the SUV of FDG was high (mean, 5.29 ± 2.72), and the SUV of 11C-choline was also high (mean, 3.69 ± 1.18). In tuberculosis patients, the SUV of FDG was high (mean, 6.45 ± 2.30), but the SUV of 11C-choline was low (mean, 2.85 ± 1.34). In atypical mycobacterial infection patients, the SUV of FDG was low (mean, 3.19 ± 2.12), and the SUV of 11C-choline was also low (mean, 1.93 ± 0.40).

Coexistence of a High-FDG/Low-11C-choline Lesion and a Low-FDG/High-11C-choline Lesion in Patients With Tuberculosis and in Patients With Atypical Mycobacterial Infection
Patients with tuberculosis and those with atypical mycobacterial infection frequently showed multiple lesions on the PET image. As a rule, the major lesion showed low SUV with 11C-choline. But the minor lesion (eg, hilar lymph nodes) occasionally showed a relatively high SUV with 11C-choline. We examined this phenomenon in detail by comparing the PET image and the pathologic specimen in the same patient. The patient presented with an SPN in the right middle lobe of the lung, but a definitive diagnosis was not obtained by ordinary examinations. A PET scan was performed, and subsequently the affected lung (right middle lobe) was resected surgically. From the surgical specimen, Mycobacterium avium complex was detected in culture. The CT and PET images of this patient are shown in Figure 4 . In the CT images, there were two lesions (lesions A and B) in the right middle lobe. In the PET images, the SUV of lesion A was high with FDG but low with 11C-choline, and the SUV of lesion B was low with FDG but high with 11C-choline (Fig 4 , top, A). In the resected lung, two lesions (ie, lesions X and Y) were found. Lesion X was localized in the central part of the lobe, presenting the appearance of a "hard" granuloma with no cavitation, and lesion Y was localized in the periphery of the lobe, surrounded by visceral pleura, presenting the appearance of pneumonia. Histologically, lesion X was characterized by clusters of macrophages and scanty capillaries, and lesion Y was characterized by abundant lymphocytes and many capillaries (Fig 4 , bottom, B). When the PET images were compared with the resected lung, lesion A corresponded with lesion X, and lesion B corresponded with lesion Y. In other words, the lesion with a high SUV of FDG and a low SUV of 11C-choline corresponded with the presence of a hard granuloma, and the lesion of low SUV of FDG and high SUV of 11C-choline corresponded with the presence of pneumonia.



View larger version (57K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4.. Top, A: CT and PET scan images of atypical mycobacterial infection of the lung caused by M avium complex (the red color in the PET images represents an SUV of >= 3). There were two lesions in the right middle lobe (ie, lesions A and B). Lesion A showed high a SUV with FDG and a low SUV with 11C-choline, and lesion B showed a low SUV with FDG and a high SUV with 11C-choline. The affected lung (ie, the right middle lobe) was resected at surgery. Bottom, B: the resected lung (the hilum on the right side) and the histology of the lesions. Macroscopically, two lesions were found. One lesion was a hard granuloma (lesion X), and the other lesion was pneumonia (lesion Y). Histologically (hematoxylin-eosin, original x20), lesion X was characterized by clusters of macrophages and scanty capillaries, and lesion Y was characterized by abundant lymphocytes and many capillaries. Lesion A corresponded with lesion X, and lesion B corresponded with lesion Y.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 References
 
The utility of PET scanning with FDG to differentiate malignant from benign (except tuberculous) SPNs is well-established.5 6 7 8 9 10 11 The rationale of FDG PET scanning for tumor imaging is based on the following principle. Molecular oxygen is an essential requirement for the cellular respiration that produces adenosine triphosphate (ATP) by oxidative phosphorylation. It is well-established that tumor cells have an alternate ATP-producing system, namely, anaerobic glycolysis, which works even in a normoxic atmosphere. Tumor cells can produce approximately the same amount of ATP from anaerobic glycolysis, using an excessive amount of glucose, as from respiration of normal cells.15 The excessive glycolysis is due to the increased activity of glucose transporters and intracellular enzymes that promote glycolysis.9 Hypoxia has an additional effect on tumor cells. The activities of glucose transporters and glycolytic enzymes of tumor cells are enhanced in hypoxia, and the tumor cells incorporate more glucose than in normoxia.16 17 18 19 The above two mechanisms are the reasons for the high uptake of FDG, a glucose analog, in tumor cells. Histologically, the tumor tissue consists of the following two basic components: (1) tumor parenchyma comprising proliferating tumor cells; and (2) supportive stroma made up of connective tissue and blood vessels for the delivery of various nutrients. Of these, molecular oxygen is the most important, because it is easily deprived with a poor blood supply. In rapidly growing tumors, the parenchyma often outgrows its blood supply, causing large areas of hypoxia.20 Tumor cells do not survive, if they are distant from the nearest capillaries by > 150 to 200 µm.21 Small tumors that adjoin the capillaries of the surrounding tissue are well-oxygenated. This is also true of the rim of large tumors. In contrast, the central parts of large tumors are often hypoxic or anoxic. The hypoxic cells are present at the interface between the normoxic and anoxic tissues. Gatenby et al22 measured the oxygen distribution in local lymph node metastases (mean tumor size, 4.4 ± 0.8 cm) in patients with head-and-neck cancer (31 patients) using a needle electrode inserted into the tumor. The oxygen tension was uniformly low (ie, < 10 mm Hg) in 13 tumors, uniformly high (ie, > 10 mm Hg) in 6 tumors, and centrally low and peripherally high in 12 tumors. The study of Gatenby et al22 showed that (1) tumor hypoxia was prominent in the center of large tumors, and (2) tumor hypoxia was enhanced by rapid growth and inadequate stroma, which varied between tumors. Their results corresponded well to our observations that (1) the SUV of FDG increased with increasing size of tumors and (2) the SUV of FDG varied between tumors of the same size.

The utility of the PET scan with 11C-choline in detecting various tumors including lung cancer is well-established.12 13 14 23 24 25 26 27 28 29 30 31 32 The rationale of 11C- choline PET scanning for tumor imaging is based on the following principles. (1) As shown by 14C-choline tracer studies, choline is incorporated into tumor cells across choline transporters and then is metabolized as follows: choline -> phosphorylcholine -> cytidine diphosphate-choline -> phosphatidylcholine. The final compound, phosphatidylcholine, is integrated into tumor cell membranes.33 34 35 36 37 38 39 40 41 (2) As shown by 31P MRI studies, choline and phosphorylcholine levels are markedly increased in many tumors. This is the result of the increased activities of choline transporters and choline kinase, and is linked to the increase in cell membrane synthesis and tumor cell proliferation.42 43 44 45 46 47 48 It is reasonable to assume that, whether tumor cells are in hypoxia or in normoxia, the 11C-choline uptake rate in tumors is an indicator of the tumor cell proliferation rate. In this context, the present results suggested that the proliferation rate of lung cancer was similar in vivo for every tumor size.

The high uptake rate of FDG in patients with pulmonary tuberculosis is well-documented.5 6 7 8 9 10 11 We found that the SUV of FDG was very high in tuberculosis patients, which was much higher than the SUV of 11C-choline. The high uptake of FDG and the low uptake of 11C-choline in tuberculosis patients are explainable based on the nature of tuberculous granuloma. During the chronic phase of tuberculosis, the granuloma is composed mainly of clusters of macrophages (ie, the hard granuloma). Blood vessels are usually scanty or completely absent in it, and the tissue is hypoxic or anoxic.49 50 51 Macrophages adapt to hypoxia and survive on anaerobic glycolysis.52 53 As a consequence, the increased glycolysis of macrophages results in a high SUV of FDG. A high uptake rate of FDG in tumor-associated macrophages (not tuberculous) has been reported by Kubota et al54 The low uptake rate of 11C-choline in tuberculosis patients is explainable in another way. During the early phase of tuberculosis, endogenous lymphocytes and macrophages proliferate fast and form a nascent granuloma. During the chronic phase, however, the nascent granuloma does not grow any more but collects a large number of monocytes (ie, exogenous macrophages) around it from the blood and grows into a hard granuloma.50 51 During this phase, the main component of the granuloma is the cluster of macrophages, which do not proliferate, and, therefore, do not need 11C-choline. We encountered a single patient with atypical mycobacterial infection who presented with two lesions, one with high 11C-choline uptake and the other with low 11C-choline uptake. A pathologic examination of the lung indicated that the high 11C-choline uptake corresponded with clusters of lymphocytes and the low 11C-choline uptake corresponded with clusters of macrophages. Generally speaking, primary lesions of tuberculosis showed low 11C-choline uptake.

On the basis of the above findings, it may be possible to diagnose an SPN presumptively, if no definitive diagnosis is obtained from pathologic and bacteriologic examinations. If there is no abnormality in PET images, there will be neither malignancy nor active inflammation in the lesion, and a wait-and-watch approach will be the best strategy. If the PET scan result is ambiguous, it is recommended that physicians prescribe antituberculous multidrug regimens55 for 3 months. If this treatment is ineffective (as shown by a repeated PET study), surgical resection is recommended. Of course, it is necessary to consider possibilities other than lung cancer and pulmonary tuberculosis in making a presumptive diagnosis of SPN.

There was a discrepancy between our previous findings12 and those of the recent study by Pieterman et al30 concerning the detectability of mediastinal lymph node metastasis from lung cancer (not of primary lung cancer) by FDG PET and 11C-choline PET scanning, where we stated that 11C-choline was more sensitive than FDG, and they stated that FDG was more sensitive than 11C-choline. This discrepancy may have arisen from the following differences in methods: (1) the use of attenuation correction, which improves image quality; (2) the possible differences in tumor size; and (3) the purity of the 11C-choline, in which residual dimethylaminoethanol may inhibit choline uptake.56 57 58 59 60 61 62 63


   Conclusions
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
References
 
Lung cancer, tuberculosis, and atypical mycobacterial infection showed different affinities for FDG and 11C-choline. This difference was explicit if the tumor size was > 1.5 cm. In lung cancer patients, the SUV of FDG was very high, and the SUV of 11C-choline was relatively high. In tuberculosis patients, the SUV of FDG was relatively high, but the SUV of 11C-choline was low. In atypical mycobacterial infection patients, the SUVs of both FDG and 11C-choline were low. If the tumor size was < 1.5 cm, the above difference was not explicit but still was observable to some extent. It would be possible to obtain a presumptive diagnosis of SPNs on the basis of the above findings, when a definitive (ie, pathologic and bacteriologic) diagnosis is not obtained.


   Acknowledgements
 
The authors thank Dr. K. Kubota, Tohoku University, for comments.


   Footnotes
 
Abbreviations: ATP = adenosine triphosphate; FDG = fluorodeoxyglucose; PET = positron emission tomography; ROI = region of interest; SPN = solitary pulmonary nodule; SUV = standardized uptake value

A part of this study was supported by the Ministry of Education, Culture, Sports, Science, and Technology under the auspices of the Atomic Energy Commission of Japan, and by the Japanese Smoking Research Foundation.

Received for publication August 12, 2002. Accepted for publication January 30, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 

  1. Lillington, GA, Caskey, CI (1993) Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 14,111-119[ISI][Medline]
  2. Swensen, SJ, Jett, JR, Payne, WS, et al An integrated approach to evaluation of the solitary nodule. Mayo Clin Proc 1990;65,173-186[ISI][Medline]
  3. Ishida, T, Yokoyama, S, Kaneko, S, et al Pulmonary tuberculoma and indications for surgery: radiographic and clinicopathological analysis. Respir Med 1992;86,431-436[ISI][Medline]
  4. Gambhir, SS, Czernin, J, Schwimmer, J, et al A tabulated summary of the FDG PET literature. J Nucl Med 2001;42,1S-93S[ISI][Medline]
  5. Malik, K, Dedhia, HV, Bishop, H, et al Clinical utility of PET-FDG imaging in detecting malignancy in pulmonary lesions [abstract]. Chest 1996;110(suppl),95S[Free Full Text]
  6. Kubota, K, Matsuzawa, J, Fujiwara, T, et al Differential diagnosis of lung cancer with positron emission tomography: a prospective study. J Nucl Med 1990;31,1927-1933[Abstract/Free Full Text]
  7. Gupta, NC, Frank, AR, Dewan, NA, et al Solitary pulmonary nodules: detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1992;184,441-444[Abstract/Free Full Text]
  8. Patz, EF, Lowe, VJ, Hoffman, JM, et al Focal pulmonary abnormalities: evaluation with F-18-fluorodeoxyglucose PET scanning. Radiology 1993;188,487-490[Abstract/Free Full Text]
  9. Knight, SB, Delberke, D, Stewart, JR, et al Evaluation of pulmonary lesions with FDG-PET: comparison of findings in patients with and without a history of prior malignancy. Chest 1996;109,982-988[Abstract/Free Full Text]
  10. Bakheet, SMB, Powe, J, Ezzart, A, et al F-18-FDG uptake in tuberculosis. Clin Nucl Med 1998;23,739-742[CrossRef][ISI][Medline]
  11. Goo, JM, Im, J-G, Do, K-H, et al Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology 2000;216,117-121[Abstract/Free Full Text]
  12. Hara, T, Inagaki, K, Kosaka, N, et al Sensitive detection of mediastinal lymph node metastasis of lung cancer with 11C-choline PET. J Nucl Med 2000;41,1507-1513[Abstract/Free Full Text]
  13. Suzuki, T, Kudo, K, Kosaka, N, et al The relationship between the SUV of 18F-FDG and 11C-choline and the tumor size in lung cancer and pulmonary tuberculoma [abstract]. J Nucl Med 2002;43(suppl),76P
  14. Kobori, O, Kirihara, Y, Kosaka, N, et al Positron emission tomography of esophageal carcinoma using 11C-choline and 18F-fluorodeoxyglucose. Cancer 1999;86,1638-1648[CrossRef][ISI][Medline]
  15. Warburg, O On the origin of cancer cells. Science 1956;123,309-314[Free Full Text]
  16. Clavo, AC, Brown, RS, Wahl, RL Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia. J Nucl Med 1995;36,1625-1632[Abstract/Free Full Text]
  17. Minn, H, Clavo, AC, Wahl, RL Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. Nucl Med Biol 1996;23,941-946[CrossRef][ISI][Medline]
  18. Clavo, AC, Wahl, RL Effects of hypoxia on the uptake of tritiated thymidine, L-leucine, L-methionine and FDG in cultured cancer cells J Nucl Med 1996;37,502-506[Abstract/Free Full Text]
  19. Burgman, P, O’Donoghue, JA, Humm, JL, et al Hypoxia-induced increase in FDG uptake in MCF7 cells. J Nucl Med 2001;42,170-175[Abstract/Free Full Text]
  20. Robbins, SL Neoplasia. Robbins, SL eds. Pathology 3rd ed. 1967,88-132 WB Saunders. Philadelphia, PA:
  21. Thomlinson, RH, Gray, LH The histologic structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 1955;9,537-549
  22. Gatenby, RA, Kessler, HB, Rosenblum, JA, et al Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1988;14,831-838[ISI][Medline]
  23. Hara, T, Kosaka, N, Shinoura, N, et al PET imaging of brain tumor with [methyl-11C]choline. J Nucl Med 1997;38,842-847[Abstract/Free Full Text]
  24. Shinoura, N, Nishijima, M, Hara, T, et al Brain tumors: detection with C-11 choline PET. Radiology 1997;202,497-503[Abstract/Free Full Text]
  25. Hara, T, Kosaka, N, Kishi, H PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39,990-995[Abstract/Free Full Text]
  26. Hara, T, Inagaki, K, Kosaka, N, et al Sensitive detection of mediastinal lymph node metastasis of lung cancer with 11C-choline PET. J Nucl Med 2000;41,1507-1513[Abstract/Free Full Text]
  27. Kotzerke, J, Prang, J, Neumaier, B, et al Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur J Nucl Med 2000;27,1415-1419[CrossRef][ISI][Medline]
  28. Jager, PL, Que, TH, Vaalburg, W, et al Carbon-11 choline or FDG-PET for staging of oesophageal cancer? Eur J Nucl Med 2001;28,1845-1849[CrossRef][ISI][Medline]
  29. Ohtani, T, Kurihara, H, Ishiuchi, S, et al Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging. Eur J Nucl Med 2001;28,1664-1670[CrossRef][ISI][Medline]
  30. Pieterman, RM, Que, TH, Elsinga, PH, et al Comparison of 11C-choline and 18F-FDG PET in primary diagnosis and staging of patients with thoracic cancer. J Nucl Med 2002;43,167-172[Abstract/Free Full Text]
  31. Inoue, T, Oriuchi, N, Tomiyoshi, K, et al A shifting landscape: what will be next FDG in PET oncology? Ann Nucl Med 2002;16,1-9[ISI][Medline]
  32. Picchio, M, Landoni, C, Messa, C, et al Positive [11C]choline and negative [18F]FDG with positron emission tomography in recurrence of prostate cancer. AJR Am J Roentgenol 2002;179,482-484[Free Full Text]
  33. Plagemann, PG Choline metabolism and membrane formation in rat hepatoma cells grown in suspension culture: III. Choline transport and uptake by simple diffusion and lack of direct exchange with phosphatidylcholine. J Lipid Res 1971;12,715-724[Abstract]
  34. Lanks, K, Somers, L, Papirmeister, B, et al Choline transport by neuroblastoma cells in tissue culture. Nature 1974;252,476-478[CrossRef][Medline]
  35. Haeffner, EW Studies on choline permeation through the plasma membrane and its incorporation into phosphatidyl choline of Ehrlich-Lettré-ascites tumor cells in vitro. Eur J Biochem 1975;51,219-228[CrossRef][ISI][Medline]
  36. Paddon, HB, Vance, DE Tetradecanoyl-phorbol acetate stimulates phosphatidylcholine biosynthesis in HeLa cells by an increase in the rate of reaction catalyzed by CTP: phosphocholine cytidyltransferase. Biochim Biophys Acta 1980;620,636-640[Medline]
  37. Pritchard, PH, Vance, DE Choline metabolism and phosphatidylcholine biosynthesis in cultured rat hepatocytes. Biochem J 1981;196,261-267[ISI][Medline]
  38. Yorek, MA, Dunlap, JA, Spector, AA, et al Effect of ethanolamine on choline uptake and incorporation into phosphatidylcholine in human Y79 retinoblastoma cells. J Lipid Res 1986;27,1205-1213[Abstract]
  39. George, TP, Morash, SC, Cook, HW, et al Phosphatidylcholine biosynthesis in cultured glioma cells: evidence for channeling of intermediates. Biochim Biophys Acta 1989;1004,283-291[Medline]
  40. Slack, BE, Richardson, I, Nitsch, RM, et al Dioctanoylglycerol stimulates accumulation of [methyl-14C]choline and its incorporation into acetylcholine and phosphatidylcholine in a human cholinergic neuroblastoma cell line. Brain Res 1992;585,169-176[CrossRef][ISI][Medline]
  41. Ishidate, K Choline transport and choline kinase. Vance, DE eds. Phosphatidylcholine metabolism 1989,9-32 CRC Press. Boca Raton, FL:
  42. Narayan, P, Jajodia, P, Kurhanewicz, J, et al Characterization of prostate cancer, benign prostatic hyperplasia and normal prostate using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report. J Urol 1991;146,66-74[ISI][Medline]
  43. Ruiz-Cabello, J, Cohen, JS Phospholipid metabolites as indicators of cancer cell function. NMR Biomed 1992;5,226-233[ISI][Medline]
  44. Nagendank, W Studies of human tumors by MRS: a review. NMR Biomed 1992;5,303-324[ISI][Medline]
  45. Kalra, R, Wade, KE, Hands, L, et al Phosphomonoester is associated with proliferation in human breast cancer: a 31P MRS study. Br J Cancer 1993;67,1145-1153[ISI][Medline]
  46. De Certaines, JD, Larsen, VA, Podo, F, et al In vivo31P MRS of experimental tumours, a review. NMR Biomed 1993;6,345-365[ISI][Medline]
  47. Katz-Brull, R, Degani, H Kinetics of choline transport and phosphorylation in human cancer cells: NMR application of the zero trans method. Anticancer Res 1996;16,1375-1380[ISI][Medline]
  48. Podo, F Tumour phospholipid metabolism. NMR Biomed 1999;12,413-439[CrossRef][ISI][Medline]
  49. Cameron, R Inflammation and repair. Robbins, SL eds. Pathology 3rd ed. 1967,31-73 WB Saunders. Philadelphia, PA:
  50. Adams, DO The granulomatous inflammatory response: a review. Am J Pathol 1976;84,161-191
  51. Dannenberg, AM, Jr, Tamashefski, JF, Jr Pathogenesis of pulmonary tuberculosis. Fishman, AP Elias, JA Fishman, JAet al eds. Fishman’s pulmonary diseases and disorders 3rd ed. 1998,2447-2471 McGraw-Hill. New York, NY:
  52. Cazin, M, Paluszezak, D, Bianchi, A, et al Effects of anaerobiosis upon morphology and energy metabolism of alveolar macrophages cultured in gas phase. Eur Respir J 1990;3,1015-1022[Abstract]
  53. Kawaguchi, T, Veech, RL, Uyeda, K Regulation of energy metabolism in macrophages during hypoxia: roles of fructose 2, 6-biphosphate and ribose 1, 5-biphosphate. J Biol Chem 2001;276,28554-28561[Abstract/Free Full Text]
  54. Kubota, R, Yamada, S, Kubota, K, et al Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33,1972-1980[Abstract/Free Full Text]
  55. Schluger, NW, Harkin, TJ, Rom, WN Principles of therapy of tuberculosis in the modern era. Rom, WN Garay, S eds. Tuberculosis 1996,751-761 Little Brown. Boston, MA:
  56. Haubrich, DR, Gerber, NH, Pflueger, AB Deanol affects choline metabolism in peripheral tissues of mice. J Neurochem 1981;37,476-482[CrossRef][ISI][Medline]
  57. Lohr, J, Acara, M Effect of dimethylaminoethanol, an inhibitor of betaine production, on the disposition of choline in the rat kidney. J Pharmacol Exp Ther 1990;252,154-158[Abstract/Free Full Text]
  58. Yavin, E Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture: ontogenesis of carrier-specific transport of choline and N-methyl-substituted choline analogs. J Neurochem 1980;34,178-183[CrossRef][ISI][Medline]
  59. Cornford, EM, Braun, LD, Oldendorf, WH Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J Neurochem 1978;30,299-308[CrossRef][ISI][Medline]
  60. Rosen, MA, Jones, RM, Yano, Y, et al Carbon-11 choline: synthesis, purification, and brain uptake inhibition by 2-dimethylaminoethanol. J Nucl Med 1985;26,1424-1428[Abstract/Free Full Text]
  61. Yorek, MA, Dunlap, JA, Spector, AA, et al Effect of ethanolamine on choline uptake and incorporation into phosphatidylcholine in human Y79 retinoblastoma cells. J Lipid Res 1986;27,1205-1213[Abstract]
  62. Hara, T, Yuasa, M Automated synthesis of [11C]choline, a positron-emitting tracer for tumor imaging. Appl Radiat Isot 1999;50,531-533[CrossRef][ISI][Medline]
  63. Mishani, E, Ben-David, I, Rosen, Y Improved method for the quality assurance of [C-11]choline. Nucl Med Biol 2002;29,359-362[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 JNMHome page
W. A. Weber
Chaperoning Drug Development with PET
J. Nucl. Med., May 1, 2006; 47(5): 735 - 737.
[Full Text] [PDF]

Home page
 JNMHome page
U. Metser, E. Miller, A. Kessler, H. Lerman, G. Lievshitz, R. Oren, and E. Even-Sapir
Solid Splenic Masses: Evaluation with 18F-FDG PET/CT
J. Nucl. Med., January 1, 2005; 46(1): 52 - 59.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (26)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hara, T.
Right arrow Articles by Niino, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hara, T.
Right arrow Articles by Niino, H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS