| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Original Research |
1 Department of Radiology, Massachusetts General Hospital, 55 Fruit St., Yawkey
6E, Boston, MA 02114.
2 Department of Orthopedic Surgery, Massachusetts General Hospital, Boston,
MA.
3 Department of Neurosurgery, Massachusetts General Hospital, Boston, MA.
4 Department of Neurology, Massachusetts General Hospital, Boston, MA.
Received February 16, 2007;
accepted after revision June 7, 2007.
Address correspondence to M. A. Bredella
(mbredella{at}partners.org).
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
MATERIALS AND METHODS. Forty-five patients with NF1 who underwent whole-body PET for suspected MPNST based on clinical symptoms or radiologic examinations were retrospectively evaluated. Ten patients underwent additional carbon-11 (11C) methionine PET because of equivocal 18F-FDG PET findings or because of a discrepancy between the FDG PET and clinical findings. PET images were evaluated for the distribution and uptake pattern, and the standardized uptake values (SUVs) were obtained. Twenty-seven patients underwent biopsy or surgery of the detected lesions and 18 patients were followed up clinically and with repeat imaging studies.
RESULTS. Fifty lesions were identified on FDG PET. There were eight false-positive results and one false-negative on FDG PET. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET in detecting MPNSTs in patients with NF1 were 95%, 72%, 71%, 95%, and 82%, respectively. Using 11C methionine PET in combination with FDG PET reduced the number of false-positive results from eight to two, which increased the specificity from 72% to 91%. In five patients, 11C methionine FDG PET contributed additional information about nontarget lesions that influenced treatment planning.
CONCLUSION. FDG PET is a sensitive technique in the detection of MPNSTs in patients with NF1. The addition of 11C methionine PET increases specificity in equivocal cases. PET may improve preoperative tumor staging by detecting metastases or second primary tumors, which often are present in patients with NF1.
Keywords: 11C methionine PET • FDG PET • neurofibromatosis type 1 • peripheral nerve sheath tumors • PET • radiotracers • soft-tissue tumors
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In contrast to MRI or CT, 18F-FDG PET can yield metabolic information that is based on increased glucose metabolism of malignant lesions [9–11]. However, FDG uptake is known to be nonspecific and high FDG accumulation has been observed not only in viable cancer cells but also in benign neoplasms, inflammatory cells, and granulation tissue. Because many tumors also overexpress amino acid transporters, alternative functional biomarkers using radio-labeled L-amino acids, such as carbon-11 (11C) methionine, have been proposed as indicators of tumor activity. Accumulation of 11C methionine is largely due to carrier-mediated transport by an L-amino acid transporter, which is highly expressed in malignant tumors. 11C methionine undergoes complex metabolism and is incorporated into proteins; therefore, increased 11C methionine uptake may reflect the metabolic needs of tumors [12, 13]. The purpose of our retrospective study was to investigate the use of FDG and 11C methionine PET in detecting MPNSTs in patients with NF1.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Patients
We identified 45 patients with NF1 who had undergone whole-body PET for
suspected MPNST based on clinical or radiographic findings. The symptoms
included growing lesions or pain, and the imaging characteristics of suspected
malignant degeneration included interval growth of a lesion or a change in
imaging characteristics, such as the presence of necrosis or hemorrhage, or
infiltration into surrounding structures. There were 23 women and 22 men, aged
17–73 years with a mean age of 37 years. Forty-five whole-body FDG PET,
nine whole-body 11C methionine PET, 10 FDG PET/CT, and one
11C methionine PET/CT were performed.
Twenty-seven patients underwent biopsy or surgical tumor resection, and the pathologic results were used as the standard of reference. The remaining 18 patients who did not undergo biopsy or surgical resection were followed up clinically and with repeat imaging for a period of 1–5 years, and the findings at clinical follow-up and on imaging studies were used for lesion verification. All patients underwent MRI or CT before PET.
Image Acquisition
Whole-body PET was performed on an ECAT HR+ scanner (CTI Molecular
Imaging). All patients fasted for at least 6 hours before image acquisition,
and blood glucose levels were measured before the injection of FDG. For FDG
PET, a dose of 15–20 mCi (555–740 MBq) of FDG was administered IV
45 minutes–1 hour before scanning. For 11C methionine PET, a
dose of 20 mCi (740 MBq) of 11C methionine was administered IV 20
minutes before scanning. Patients were positioned supine on the scanner, and
emission images were acquired in six or seven bed positions from mandible to
mid thigh or to the level of the ankles in patients with lower extremity
lesions. Transmission images obtained with a rotating germanium-68 rod sources
were used for attenuation correction. Images were reconstructed using the
ordered subset expectation maximization (OSEM) algorithm.
Combined PET/CT studies were performed with a 16-section hybrid PET/CT gantry (Biograph Sensation 16, Siemens Medical Solutions) that comprises a high-performance 16-MDCT scanner with a lutetium oxyorthosilicate–based PET scanner. The PET image spatial resolution was 5.0-mm full width at half maximum, and the section thickness was 3.5 mm. Patients fasted for at least 6 hours before image acquisition, and blood glucose levels were measured before the injection of FDG. One hour before scanning, patients drank two 10-oz (294 mL) cups of water, which served as negative contrast material. For FDG PET/CT, a dose of 15–20 mCi (555–740 MBq) of FDG was administered IV 45 minutes–1 hour before scanning. For 11C methionine PET/CT, a dose of 20 mCi (740 MBq) of 11C methionine was administered IV 20 minutes before scanning. Patients were positioned supine on the scanner, and emission images were acquired in six or seven bed positions from the mandible to mid thigh or to the level of the ankles in patients with lower extremity lesions. Images were reconstructed with Fourier rebinning and attenuation-weighted OSEM. A low-dose CT scan was obtained before PET primarily for attenuation correction while patients held their breath in mid expiration and included an area from the mandible to mid thigh or to the level of the ankles in those with of lower extremity lesions. Diagnostic contrast-enhanced CT was performed using 2.5-mm sections subsequent to PET/CT after the administration of 100 mL of IV contrast material (iopamidol [Isovue 300, Bracco Diagnostics]) at an injection rate of 2 mL/s.
Image Analysis
Semiquantitative and qualitative evaluations of PET images were performed
on a high-resolution workstation (Reveal-MVS, Mirada Solutions) by two
independent investigators who were blinded to the clinical and pathologic
results. The images were displayed in rotating maximum intensity projections
and in axial, coronal, and sagittal planes. Semiquantitative analysis of FDG
uptake of softtissue lesions was performed in 41 lesions in 36 patients by
creating a region of interest over the area of maximal radiotracer
activity.
Maximum standardized uptake values (SUVs) were automatically generated
according to the following equation:
 |
Statistical Analysis
The recorded data were analyzed using statistical database software (JMP,
SAS Institute). The findings on the PET images and SUVs of benign peripheral
nerve sheath tumors and MPNSTs were correlated with the final diagnosis of the
lesion as malignant or benign. Sensitivity, specificity, positive predictive
value (PPV), negative predictive value (NPV), and accuracy were calculated.
The Student's t test was used to determine whether there was a
statistically significant difference between the SUVs for benign peripheral
nerve sheath tumors and MPNSTs. A difference with a p value of <
0.05 was considered to be statistically significant. Interobserver agreement
was measured using kappa statistics.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Qualitative PET Analysis
Fifty lesions were identified in 45 patients. Based on visual inspection of
the suspected lesions, 26 tumors were characterized as benign and 24 tumors as
malignant. The malignant lesions showed intense radiotracer uptake (Fig.
1A,
1B,
1C), whereas the benign
peripheral nerve sheath tumors showed only mildly increased or no increased
uptake on FDG PET. One patient with a known large plexiform neurofibroma of
the lower extremity showed low-level uptake of the plexiform neurofibroma with
two small foci of increased FDG uptake within the lesion, which resulted in
complete resection of the neurofibroma, and foci of malignant degeneration
were found at surgery (Fig. 2A,
2B).
|
|
|
|
|
|
Ten patients underwent 11C methionine PET after FDG PET because of equivocal FDG PET findings—that is, uptake equal to or slightly greater than liver uptake—or because of a discrepancy between the FDG PET and clinical findings, such as abnormal FDG uptake without a change in clinical symptoms. Nine of these 10 patients showed increased uptake on the initial FDG PET scan that was suspicious for malignancy. In six of these nine patients, there was no abnormal uptake on subsequently performed 11C methionine PET, and the surgery or biopsy result (n = 4) or the clinical and imaging follow-up (n = 2) was negative in all six patients (Figs. 4A, 4B and 5A, 5B, 5C, 5D). One patient showed increased uptake on FDG PET and on 11C methionine PET that was suspicious for malignancy; however, surgery showed a benign peripheral nerve sheath tumor. Two patients with increased FDG and 11C methionine uptake were found to have MPNSTs at surgery. One patient had no evidence of abnormal radiotracer uptake on FDG and 11C methionine PET, and clinical and imaging follow-up was negative for malignancy.
|
|
|
|
|
|
|
|
Quantitative PET Analysis
SUVs were measured in 41 lesions in 36 patients. SUVs could not be measured
in nine lesions in the nine remaining patients because the images could be
reviewed only on a workstation that did not have SUV measurement capability.
Interobserver agreement (
= 0.95) was classified as very good. The SUVs
for MP-NST ranged from 3.8 to 13.0 with a mean of 8.5 ± 0.63 SEM
(standard error of the mean) on FDG PET. Benign peripheral nerve sheath tumors
showed SUVs ranging from 0 to 5.3 with a mean of 1.5 ± 0.37 SEM on FDG
PET. The difference between the SUV values of benign and malignant lesions was
statistically significant (p < 0.001, Student's t test)
(Fig. 7).
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Although MRI and CT have been shown to be excellent tools for the noninvasive evaluation of tumor extent, they are commonly not reliable in accurately characterizing a lesion as benign or malignant [15]. Surgical resection of the entire nerve sheath tumor is often not feasible because of the associated morbidity, and biopsies may yield false-negative results due to sampling error. In this context, metabolic imaging techniques such as FDG PET have received closer scrutiny because they can provide information about tumor metabolism. FDG PET has been found to be helpful in detecting tumor recurrence in patients with sarcomas and in differentiating benign from malignant neoplasms [16–18].
Preliminary studies and case reports have shown that FDG PET is a useful imaging technique in detecting malignant change in peripheral nerve sheath tumors in patients with NF1 [3, 19–21]. In our study, FDG PET was very sensitive in detecting MPNSTs in patients with NF1 (sensitivity = 95%). The only false-negative case was a poorly differentiated carcinoma with large areas of necrosis that showed no abnormal FDG uptake. However, the specificity of PET was only 72% and several benign neurofibromas were classified as malignant on the basis of a visual analysis and SUV measurements because of an overlap between benign and malignant lesions.
The overlap of SUVs for benign and malignant lesions in patients with NF1 is known and is the factor that led us to use 11C methionine PET. In equivocal cases, the addition of 11C methionine PET was helpful, improving specificity from 72% to 91%. The mechanism of 11C methionine uptake in tumors is influenced by amino acid transport, which correlates with cell proliferation. Increased uptake of 11C methionine has been suggested to reflect increased transport; transmethylation rate; and, to some extent, protein synthesis of malignant tissue [12, 13]. Radiolabeled methionine, by providing relevant information about amino acid transport, has been found useful for the early assessment of treatment response in patients with intracranial neoplasms [22, 23]. To our knowledge, no study has been performed using 11C methionine for the detection of malignant degeneration in soft-tissue tumors.
The advantages of 11C methionine over FDG include low uptake in nonviable cells and macrophages and better correlation with tumor proliferative activity. A short-coming is the short half-life of 20 minutes, which requires an on-site cyclotron. In our study, 11C methionine provided additional information about tumor metabolism and increased specificity for MPNST detection in equivocal cases.
Overall, the mean SUVs were significantly higher for malignant lesions (8.5 ± 0.63 SEM) than for benign lesions (1.5 ± 0.37 SEM) on FDG PET. Also, interobserver agreement was high, making PET a reliable technique for evaluating malignant transformation of plexiform neurofibromas in patients with NF1. In a study of NF1-related MPNSTs, Brenner et al. [3] found that tumor SUV on FDG PET was an important predictor for survival: Patients with tumors showing an SUV of > 3 had a shorter survival than those with tumors showing an SUV of < 3.
PET and PET/CT were equally sensitive in the detection of MPNSTs. However, PET/CT proved to be useful in biopsy planning. MP-NSTs often contain heterogeneous areas of tumor, so biopsy of a small part of the lesion does not always reflect the overall character of the lesion and high-grade areas may be missed. We therefore used the fused PET/CT images for percutaneous CT-guided biopsy planning, which allowed us to target the most metabolically active area of the tumor. Coregistration of PET and CT images also allowed accurate interpretation of the anatomic location of abnormal radiotracer uptake, especially in complex anatomic regions, such as the head and neck area and the abdomen.
In five patients, FDG PET contributed additional information about nontarget lesions that influenced treatment planning. In one of these patients, unsuspected metastatic disease from MPNST was found within the soft tissues and lung, and in another patient, a colonic adenocarcinoma was detected. In a third patient, an unsuspected MPNST was found at routine follow-up. The remaining two patients were found to have a GIST, which has an increased incidence in patients with NF1 [24–28]. We therefore recommend that PET of the whole body be performed in patients with NF1.
Our study had several limitations. The first is the retrospective nature of the study. Second, surgical and histopathologic confirmation was not available in all patients. Indeed, in 18 of the 45 patients, clinical follow-up and repeat imaging studies were used as the alternate standard of reference. However, patients were followed up over a period of 1–5 years and none of the patients developed MPNSTs.
In conclusion, the detection of MPNSTs in patients with NF1 using clinical characteristics and MRI or CT alone is extremely difficult. The results of our study indicate that FDG PET is a highly sensitive and noninvasive method for detecting malignant change in peripheral nerve sheath tumors in patients with NF1. The addition of 11C methionine PET increases specificity in equivocal cases. PET provides metabolic information about the whole body and may improve preoperative tumor staging by detecting metastases or second primary tumors, which are often present in patients with NF1. PET is also able to guide biopsy and direct appropriate therapy in positive cases obviating repetitive surgery and biopsy in negative cases.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V.-F. Mautner, F. A. Asuagbor, E. Dombi, C. Funsterer, L. Kluwe, R. Wenzel, B. C. Widemann, and J. M. Friedman Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1 Neuro-oncol, August 1, 2008; 10(4): 593 - 598. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
