Todd M. Blodgett, MD

PET/CT continues to find new applications in detection and monitoring of breast, cervical, and ovarian carcinoma. An estimated 211,000 new cases of invasive breast carcinoma, with almost 41,000 deaths, are expected to occur in the U.S. during 2007. Breast carcinoma is the most frequently diagnosed malignancy in women and ranks second in terms of cancer deaths after lung cancer.

. Although promising results are emerging for FDG-PET to evaluate primary breast masses, the technique has not been used successfully for this application. Early studies by Wahl et al and other groups suggested that PET may have a high sensitivity for detecting primary breast lesions larger than 1 cm, but in the largest study to date, Avril and colleagues found that up to 40% of primary breast carcinomas smaller than 2 cm were not seen with PET imaging.1-4

The overall sensitivity and specificity for breast lesions, calculated by a Blue Cross/Blue Shield technology assessment examining 13 studies with 606 patients, were 89% and 80%, respectively.5 Based on the high incidence of breast cancer, PET's potential false-negative rate, and its cost compared with mammography, PET is not currently recommended to evaluate primary breast masses. It is not covered for reimbursement by Medicare.

Although PET is not sufficiently sensitive for detecting primary breast lesions, most studies have suggested that it does have a high positive predictive value, so that a positive lesion (even incidentally discovered) should be considered malignant until proven otherwise.

. The presence of tumor within axillary lymph nodes is an important prognostic indicator in patients with breast cancer. Anatomic imaging modalities are not useful because there is often microscopic involvement. Unfortunately, micrometastatic involvement is also a major limitation for current PET and PET/CT scanners.

Adler et al found a sensitivity and negative predictive value of 95% and an overall accuracy of 77% in a study of 50 patients.6 Avril and colleagues evaluating 51 patients found a sensitivity and specificity of 79% and 96%, respectively. When only patients with late-stage disease were considered (primary breast tumor > 2 cm, > pT1), however, the sensitivity and specificity of FDG-PET increased to 94% and 100%, respectively.7

The only PET/CT study evaluating axillary lymph node staging found in 15 patients a sensitivity, specificity, and accuracy of 80%, 90%, and 87%, respectively.8 Given the combined sensitivity limitations of both PET and CT for detecting micrometastases, it is unlikely that combining the two modalities will overcome these limitations or replace sentinel lymph node scintigraphy.9-13 Medicare does not cover PET staging of axillary nodes.

In contrast to the limited role PET plays in evaluating the axilla, it has been shown to be more useful for identifying unsuspected internal mammary lymph nodes and distant metastases (Figure 1). Although little evidence in the literature compares PET/CT with PET and CT performed separately, it is likely that PET/CT will improve precise localization of suspected metastatic lesions identified on PET.

. Local or regional recurrence occurs in up to 30% of breast cancer patients after initial therapy, and imaging is crucial for surveillance and detection of early recurrence. It is clear from a number of studies that FDG-PET has a very high sensitivity (92% to 100%) for detecting recurrence, and it is reimbursed by Medicare.14-17 Depending on when PET or PET/CT is performed in the post-therapeutic period, however, the specificity tends to be lower (72% to 82%). Several studies have shown that PET is useful to detect unsuspected malignancy in bone and lymph nodes but somewhat less sensitive than CT in detecting local recurrence. False positives from physiologic uptake are a problem with PET, but these can be reduced significantly with combined PET/CT.

For the detection of osseous metastases, it is likely that PET and PET/CT will play a complementary role to traditional bone scintigraphy, rather than replace it. A preliminary report showed PET/CT detected lesions in 77% of patients suspected of recurrence based on clinical exam or tumor markers. Results led to a change in clinical management in 36%.18 Another group reported a patient-based sensitivity and specificity of 96% and 89%, respectively, which is in the range of most reported FDG-PET sensitivities but represents an improvement in specificity over PET alone.19 In general, PET is more sensitive for osteolytic lesions, and traditional bone scanning is more sensitive for osteoblastic lesions.

. PET and PET/CT are indicated for evaluating response to therapy in patients with breast carcinoma. Several studies have demonstrated the ability of FDG-PET to differentiate potential responders from nonresponders.20-24 Often, with anatomic imaging studies, bulky areas of disease are difficult to evaluate early following therapy. PET/CT can accurately localize areas of persistent disease, as well as areas with persistent uptake for potential biopsy localization. This indication is covered by Medicare.

Early experience with whole-body dedicated PET imaging in gynecologic malignancies has demonstrated a similar or, in some studies, slightly higher sensitivity, specificity, and accuracy compared with CT and MRI in staging these patients, as well as in the detection of recurrent disease.25-29 PET/CT has overcome many of the limitations of dedicated PET imaging, markedly improving anatomic localization and differentiation between pathologic and physiologic FDG activity.

Until recently, a major limitation to the use of combined PET/CT in gynecologic malignancies has been the lack of insurance reimbursement, with the exception of cervical carcinoma staging. Reimbursement for all indications of cervical and ovarian cancer is now available through the National Oncologic PET Registry.

. FDG-PET and PET/CT are not routinely used for the initial evaluation of a cervical or ovarian mass. Almost all patients referred for PET or PET/CT have been previously diagnosed with cervical or ovarian carcinoma.

. At the University of Pittsburgh Medical Center, we have scanned approximately 400 patients with ovarian, cervical, or endometrial cancer, in different stages of their disease process. Although we have not performed a definitive analysis of these data, preliminary results are encouraging. Of the initial 56 patients with primary and recurrent gynecologic malignancies (35 ovarian, 21 cervical) who were evaluated for treatment planning, PET/CT identified additional lesions compared with their traditional pretreatment clinical CT in 10 of 21 (48%) cervical cancer patients and 28 of 35 (80%) ovarian cancer patients. Although seemingly impressive, the actual significance of these findings is in the effect they had in changing patient management in 35 of 56 (63%) patients.14-15

Another application particularly suited for PET/CT is radiation therapy planning. PET/CT offers the unique ability to more accurately define tumor extent and target volumes (Figure 2). Although not all patients with gynecologic malignancies are being sent for pretreatment PET/CT, they are increasingly being referred for this reason. Our experience is that PET/CT offers a much more accurate definition of the extent of disease and target volumes for radiation therapy planning in this patient population, although more studies are needed to confirm these findings.

. Several recent studies have shown marked improvements in the utility of PET/CT for restaging patients with gynecologic malignancies, particularly those with ovarian carcinoma.30-36 Figure 3 demonstrates a patient who was referred for suspected recurrence of ovarian cancer due to an increase in her CA-125 level. A CT scan performed at an outside institution just prior to her PET/CT study was interpreted as normal, even in retrospect. After an abnormality was identified along the gastrosplenic ligament on PET/CT, this patient was sent for a CT-guided biopsy of the lesion. The lesion could not be identified while the patient was on the biopsy table, however. Attempts were made to provide the fused PET/CT images to the interventional suite to help guide the biopsy, but the patient eventually refused the exam and was lost to follow-up. She returned over a year later for a repeat PET/CT study, which showed diffusely progressive metastatic disease, including abdominal lymphadenopathy and multiple masses within the mesentery. Now we routinely send fused images with the patient if she is going to have surgery or biopsies performed, particularly when we feel the fused image would be helpful in guiding the physician who is performing the procedure.

While more studies will help define the multiple potential roles of PET/CT in gynecologic malignancies, we are already seeing a significant increase in the number of affected patients as a result of the success we have demonstrated to date. Of course, challenges remain for PET/CT, as it retains some of the individual limitations of each separate modality.

Neither PET nor CT, for example, is yet capable of detecting microscopic disease-PET because of spatial resolution limitations, and CT because of the absence of an identifiable anatomic correlate. False-positive studies will continue to be a problem because of the identification of hypermetabolic nodes that are "reactive" but do not actually contain tumor. In our experience, however, these cases are the exception, and the value gained from the combined modalities far outweighs any potential limitations.

The future of PET imaging lies in the development of more specific imaging probes. As this development progresses, the need for combined anatomic and functional imaging modalities will become imperative because of the lack of uptake in background tissue and the increasing absence of anatomic detail. Regardless of the specificity of the probes developed, it is becoming evident that combined PET/CT imaging is having an increasingly significant impact on healthcare in oncology.

Dr. Blodgett is an oncologic imaging fellow, and Dr. Ryan is a research assistant, both in the radiology department at the University of Pittsburgh Medical Center.

Wahl RL, Cody RL, Hutchins GD, Mudgett EE. Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1991;179(3):765-770.

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Adler LP, Crowe JP, al-Kaisi NK, Sunshine JL. Evaluation of breast masses and axillary lymph nodes with [F-18] 2-deoxy-2-fluoro-D-glucose PET. Radiology 1993;187(3):743-750.

Avril N, Rose CA, Schelling M, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 2000;18(20):3495-3502.

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Adler LP, Faulhaber PF, Schnur KC, et al. Axillary lymph node metastases: screening with [F-18]2-deoxy-2-fluoro-D-glucose (FDG) PET. Radiology 1997;203(2):323-327.

Avril N, Dose J, Janicke F, et al. Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose. J Natl Cancer Inst 1996;88(17):1204-1209.

Wang Y, Yu J, Liu J, et al. PET-CT in the diagnosis of both primary breast cancer and axillary lymph node metastasis: initial experience. Int J Radiat Oncol Biol Phys 2003;57 (Suppl):362-363.

Lovrics PJ, Chen V, Coates G, et al. A prospective evaluation of positron emission tomography scanning, sentinel lymph node biopsy, and standard axillary dissection for axillary staging in patients with early stage breast cancer. Ann Surg Oncol 2004;11(9):846-853.

Fehr MK, Hornung R, Varga Z, et al. Axillary staging using positron emission tomography in breast cancer patients qualifying for sentinel lymph node biopsy. Breast J 2004;10(2):89-93.

van der Hoeven JJ, Hoekstra OS, Comans EF, et al. Determinants of diagnostic performance of [F-18]fluorodeoxyglucose positron emission tomography for axillary staging in breast cancer. Ann Surg 2002;236(5):619-624.

Guller U, Nitzsche EU, Schirp U, et al. Selective axillary surgery in breast cancer patients based on positron emission tomography with 18F-fluoro-2-deoxy-D-glucose: not yet! Breast Cancer Res Treat 2002;71(2):171-173.

Yang JH, Nam SJ, Lee TS, et al. Comparison of intraoperative frozen section analysis of sentinel node with preoperative positron emission tomography in the diagnosis of axillary lymph node status in breast cancer patients. Jpn J Clin Oncol 2001;31(1):1-6.

Goerres GW, Michel SC, Fehr MK, et al. Follow-up of women with breast cancer: comparison between MRI and FDG PET. Eur Radiol 2003;13(7):1635-1644.

Gallowitsch HJ, Kresnik E, Gasser J, et al. F-18 fluorodeoxyglucose positron-emission tomography in the diagnosis of tumor recurrence and metastases in the follow-up of patients with breast carcinoma: a comparison to conventional imaging. Invest Radiol 2003;38(5):250-256.

Suarez M, Perez-Castejon MJ, Jimenez A, et al. Early diagnosis of recurrent breast cancer with FDG-PET in patients with progressive elevation of serum tumor markers. Q J Nucl Med 2002;46(2):113-121.

Moon DH, Maddahi J, Silverman DH, et al. Accuracy of whole-body fluorine-18-FDG PET for the detection of recurrent or metastatic breast carcinoma. J Nucl Med 1998;39(3):431-435.

Buck A, Wahl A, Eicher U, et al. Combined morphological and functional imaging with FDG-PET/CT for restaging breast cancer-impact on patient management. J Nucl Med 2003;44S:78P.

Lind P, Igerc I, Beyer T, et al. Advantages and limitations of FDG PET in the follow-up of breast cancer. Eur J Nucl Med Mol Imaging 2004;31 Suppl 1:S125-34.

Burcombe RJ, Makris A, Pittam M, et al. Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer 2002;38(3):375-379.

Schelling M, Avril N, Nahrig J, et al. Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 2000;18(8):1689-1695.

Bassa P, Kim EE, Inoue T, et al. Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med 1996;37(6):931-938.

Jansson T, Westlin JE, Ahlstrom H, et al. Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation? J Clin Oncol 1995;13(6):1470-1477.

Wahl RL, Zasadny K, Helvie M, et al. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993;11(11):2101-2111.

Kubik-Huch RA, Dorffler W, von Schulthess GK, et al. Value of (18F)-FDG positron emission tomography, computed tomography, and magnetic resonance imaging in diagnosing primary and recurrent ovarian carcinoma. Eur Radiol 2000;10(5):761-767.

Zimny M, Siggelkow W, Schroder W, et al. 2-[Fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography in the diagnosis of recurrent ovarian cancer. Gynecol Oncol 2001;83(2):310-315.

Hubner KF, McDonald TW, Niethammer JG, et al. Assessment of primary and metastatic ovarian cancer by positron emission tomography (PET) using 2-[18F]deoxyglucose (2-[18F]FDG). Gynecol Oncol 1993;51(2):197-204.

Karlan BY, Hoh C, Tse N, et al. Whole-body positron emission tomography with (fluorine-18)-2-deoxyglucose can detect metastatic carcinoma of the fallopian tube. Gynecol Oncol 1993;49(3):383-388.

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Articles

PET/CT finds footing in breast, cervical, and ovarian carcinoma

Several oncologic imaging modalities have evolved significantly since CT was developed in 1973. Although CT provides a noninvasive method for evaluating cancer patients, first-generation scanners were limited in their speed of data acquisition and spatial resolution. Current multislice CT scanners can evaluate a patient completely, with exquisite anatomic detail, in as little as 15 to 30 seconds.

When MR imaging became available in 1983, it made further characterization of suspected malignant lesions possible, often adding complementary information to that found on CT.

Ultrasound, too, offers additional information for evaluation and characterization of several potential malignant lesions. Ultrasound, CT, and MR remain major imaging modalities in clinical oncology, but they generally offer little information regarding the metabolic derangements of tumors. With the use of 2-fluoro-deoxyglucose (FDG) PET imaging, a radioactive glucose analog is injected into patients, and a sensitive coincidence detector system maps the radioactivity.

It has been known since Warburg's observations in the 1930s that many tumors are hypermetabolic compared with surrounding normal tissue, and, therefore, visualization of many tumor types became possible with FDG-PET.1 However, PET imaging provides only limited anatomic detail, and some tumors do not readily take up FDG, making them relatively or absolutely undetectable by FDG-PET (Table 1).

The underlying aberration of cancer is abnormal cellular division and proliferation, which indirectly causes increased metabolic rates for most malignancies. The anatomic findings identified on CT and/or MR in general tend to be later manifestations relative to the functional changes in tumors. FDG-PET can potentially demonstrate metabolic abnormalities earlier in the disease process and enable further characterization of many malignant lesions.

It makes sense, then, that combining an anatomic scanner (CT or MR) with a functional scanner (PET) might be the optimal imaging modality for evaluating oncologic patients. In 1998, the first prototype combined PET/CT scanner was developed at the University of Pittsburgh, and clinical PET/CT scanners became commercially available in 2001.

Although FDG-PET imaging has been in existence since 1976, it wasn't until 1998, when the Centers for Medicare and Medicaid Services announced reimbursement for FDG-PET for several indications (Table 2), that the modality began to be used more frequently. Several valuable clinical applications for FDG- PET can extend to many of the covered indications (Table 3).

- Screening. A few large studies have examined the utility of FDG-PET as a potential oncologic screening tool in asymptomatic patients, with a 2% to 3% detection rate of unsuspected malignancies in the general population.2 The current cost of the procedure outweighs the potential benefits, however, and prohibits its widespread use as a cancer screening modality. False-positive studies are an additional undesirable consequence of screening that also outweighs the potential benefits, due to excessive costs of further evaluation and morbidity from biopsies and other unnecessary invasive diagnostic procedures.

- Carcinoma of unknown primary. Medicare and most third-party payers do not reimburse for FDG-PET imaging of carcinoma of unknown primary (CUP), although up to 5% of all cancer patients receive this diagnosis. FDG-PET has been used to detect and localize primary malignancies, with a detection rate ranging from 43% to 48%.3,4 PET has been shown to influence management in up to 69% of patients for whom it is used to evaluate CUP. Although FDG-PET can be helpful in diagnostically challenging CUP patients, one study reported two-false negative PET exams, reinforcing the fact that absence of an abnormality on FDG-PET does not exclude the presence of disease.

- Differentiating benign from malignant lesions. The most common indication for a PET scan is to evaluate a radiographically indeterminate solitary pulmonary nodule. FDG-PET has been shown in several studies to be more accurate in differentiating benign from malignant nodules larger than 1 cm.5-9 The sensitivity and specificity for all lung nodules is approximately 97% and 78%, respectively, as reported in a meta-analysis evaluating 40 studies and 1474 lung nodules examined with FDG-PET.9

Although FDG-PET can be used to evaluate hepatic, pancreatic, splenic, and other masses or nodules in patients without a pathologic diagnosis of malignancy, a negative PET study in this patient population is often denied by third-party payers. They argue that the test was performed for the evaluation of an unknown primary tumor, currently a nonreimbursable CMS indication.

- Staging following initial diagnosis. FDG-PET has been shown to have a higher sensitivity and at times a higher specificity than CT and/or MR imaging for evaluation of many FDG-avid malignancies, including lung, colorectal, esophageal, and head and neck cancer, as well as lymphoma and melanoma.10-22 The evidence is compelling enough in the staging of these malignancies that the addition of PET imaging has been recommended as the standard of care rather than optional evaluation (Figure 1).23

- Restaging. Several studies have also shown the utility of FDG-PET for many restaging applications in patients with various malignancies. These applications include differentiation of scar from recurrent tumor, evaluation of patients with elevated tumor markers, and surveillance of asymptomatic patients following therapy.24-30 Further, therapy monitoring (Figures 2 and 3) and tracking overall response to therapy are important restaging applications in which evaluation of early metabolic changes following chemotherapy has been shown to be more useful than using traditional anatomic imaging modalities.31-40

The main limitations of PET imaging are the lack of anatomic detail and the inability to evaluate for the presence of microscopic disease and smaller non-FDG-avid tumors. The absolute level of spatial resolution is approximately 5 to 6 mm using current technology.

The remaining limitations of PET imaging are primarily those of FDG, the only FDA-approved oncologic radiotracer. Although many tumor types take up FDG, due to their inherent metabolic upregulation, several malignancies have much less or no FDG uptake. Among these are hepatocellular carcinoma, neuroendocrine tumors, and even some lung cancers, such as bronchoalveolar cell carcinoma among others. (Figure 4).

Several other radiotracers in development focus on examining other cellular processes. One promising radiotracer is 3' deoxy-3'-[F-18] fluorothymidine (FLT), a thymidine analog that reflects cellular proliferation rather than metabolism, although data supporting its routine use are limited.41-46 FLT is also taken up intensely by the liver and bone marrow physiologically, making it an unlikely candidate for single radiotracer evaluation.

CT is the imaging modality most commonly used to evaluate patients with cancer. It is ubiquitous in the medical imaging community and offers superb visualization of internal structures. Current 16 to 64-slice CT scanners provide the ability to obtain true isotropic data sets that permit manipulation of data and visualization of anatomy in axial, coronal, or sagittal planes without loss of anatomic resolution. Volumetric analysis of pulmonary nodules and continued development of CT colonography and other potential screening applications, which have helped reduce the number of more invasive procedures, will undoubtedly play an increasing role.

Using different protocols with intravenous and oral contrast and obtaining data during different phases of contrast enhancement, CT can accurately evaluate many tumors.

MRI is used much less frequently than CT and PET for oncologic applications, with the exception of primary and metastatic brain tumors, for which it is the diagnostic imaging modality of choice. However, MR offers complementary information in many oncologic applications, including liver, renal, and pancreatic mass evaluation. In the case of indeterminate adrenal nodules and masses, MR imaging can help differentiate adrenal adenoma from other, more potentially malignant diagnoses.

The primary limitation of CT is its inability to evaluate the metabolic derangements of tumors. The anatomic detail is much better than can be obtained with PET, but post-treatment changes due to surgery and/or radiation therapy may appear identical to recurrent malignancy on CT. On PET imaging, however, scarring should have no FDG uptake and can easily be differentiated from FDG-avid tumor. In addition, most small malignant lymph nodes, prior to becoming enlarged, appear identical to normal lymph nodes on CT and often on MR. The criteria for differentiating a benign from malignant lymph node, including necrosis, enhancement, and mass effect, are all late manifestations of malignant involvement.

MR imaging has logistical limitations, including the relative inability to scan claustrophobic patients and those with contraindications such as implanted pacemakers and other metallic devices. Otherwise, MR's limitations are similar to those of CT, including the relative inability to determine involvement of normal-sized malignant lymph nodes and to distinguish post-treatment changes from recurrent tumor. Although more functional MR studies and protocols are being developed and performed, MR generally provides limited metabolic/functional information in comparison with PET imaging.

Given the increasing utilization and acceptance of PET imaging in oncology, but also its severe limitations without anatomic correlation, combining PET and CT into a single examination is obviously beneficial. But there are many unexpected synergistic benefits, as well. Performing combined PET/CT rather than PET and CT separately not only consolidates the patient's imaging procedures but also expedites scan times and patient throughput because it avoids a separate PET transmission scan.

The most notable clinical benefit of combined PET/CT is improved lesion localization. Several authors report significant changes and improvement in lesion localization when comparing the PET portion of a PET/CT with fused PET/CT images.47-51

One of the most frustrating aspects of FDG-PET imaging alone is the lack of anatomic landmarks and the inherent uncertainty in localizing areas of FDG accumulation. It is often difficult or impossible to differentiate specific areas of FDG uptake as physiologic or pathologic, given the variable physiologic uptake of FDG in bowel, skeletal muscle, glands, and the genitourinary system.52 By fusing accurately coregistered PET and CT data sets, PET/CT significantly reduces the magnitude of mislocalization of FDG uptake and improves the confidence level of the interpreting physician in precisely localizing lesions.53 Published case reports and series also document how visualizing the fused images helped to resolve potential misinterpretation of benign processes as malignant.54-63

Several reports in the last three years have demonstrated the improved performance and the incremental value of PET/CT over PET, CT, or PET and CT performed separately for staging patients with Hodgkin's and non-Hodgkin's lymphoma and lung and colorectal cancer.64-70

PET/CT has been reported to affect patient management, particularly in radiation therapy evaluation and planning.47,68,71-74 PET/CT scanners were designed to accommodate flat radiation therapy planning pallets. As long as patient movement is minimized between the two scans, accurate coregistration of the two data sets is possible using fusion software, which most radiation therapy planning systems offer. With accurate coregistration, it is possible to view any blended combination of data.

Therapy planning for patients undergoing radiation has traditionally been based solely on anatomic information from a CT scan performed with an approved radiation therapy immobilization pallets. With PET/CT performed with a flat pallets, both the CT and PET data sets can be exported from the acquisition workstation and imported into radiation planning software systems. The patient's radiation therapy plan can then be designed with consideration of not only anatomic information but also metabolic data. This is particularly important for lesions that do not demonstrate a definite anatomic abnormality. When a lesion or the extent of a lesion cannot be adequately identified on the CT portion of the exam, radiation oncologists can integrate the metabolic information from PET for their contouring.

One of the most beneficial applications of combined PET/CT is in restaging patients who have undergone extensive surgery or radiation therapy, both of which tend to distort normal anatomy and cause inflammatory tissue changes. The importance and utility of PET/CT in the restaging of several malignancies, including head and neck, colorectal, thyroid, ovarian cancer, and lymphoma, have also has been reported.64,67,75-77

1. Warburg O. The metabolism of tumors. Science 1931:129-169.

2. Yasuda S, Ide M, Fujii H, et al. Application of positron emission tomography imaging to cancer screening. Br J Cancer 2000;83(12):1607-1611.

3. Mantaka P, Baum RP, Hertel A, et al. PET with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with cancer of unknown primary (CUP): influence on patients' diagnostic and therapeutic management. Cancer Biother Radiopharm 2003;18(1):47-58.

4. Rades D, Kuhnel G, Wildfang I, et al. Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management. Ann Oncol 2001;12(11):1605-1609.

5. Herder GJ, Golding RP, Hoekstra OS, et al. The performance of (18)F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004;31(9):1231-1236.

6. Belohlavek O, Kosatova K, Melinova L, et al. Metabolic characterisation of solitary pulmonary nodules by positron emission tomography with FDG-preliminary report. Nucl Med Rev Cent East Eur 2001;4(2):97-100.

7. Bury T, Dowlati A, Paulus P, et al. Evaluation of the solitary pulmonary nodule by positron emission tomography imaging. Eur Respir J 1996;9(3):410-414.

8. Gambhir SS, Shepherd JE, Shah BD, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol 1998;16(6):2113-2125.

9. Gould MK, Maclean CC, Kuschner WG, et al. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285(7):914-924.

10. Wahl RL, Quint LE, Greenough RL, et al. Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation. Radiology 1994;191(2):371-377.

11. Laubenbacher C, Saumweber D, Wagner-Manslau C, et al. Comparison of fluorine-18-fluorodeoxyglucose PET, MRI and endoscopy for staging head and neck squamous-cell carcinomas. J Nucl Med 1995;36(10):1747-1757.

12. Steinert HC, Hauser M, Allemann F, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology 1997;202(2):441-446.

13. Adams S, Baum RP, Stuckensen T, et al. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 1998;25(9):1255-1260.

14. Schrevens L, Lorent N, Dooms C, Vansteenkiste J. The role of PET scan in diagnosis, staging, and management of non-small cell lung cancer. Oncologist 2004;9(6):633-643.

15. Halter G, Buck AK, Schirrmeister H, et al. Lymph node staging in lung cancer using [18F]FDG-PET. Thorac Cardiovasc Surg 2004;52(2):96-101.

16. Kantorova I, Lipska L, Belohlavek O, et al. Routine (18)F-FDG PET preoperative staging of colorectal cancer: comparison with conventional staging and its impact on treatment decision making. J Nucl Med 2003;44(11):1784-88.

17. Wahl RL. Current status of PET in breast cancer imaging, staging, and therapy. Semin Roentgenol 2001;36(3):250-260.

Todd M. Blodgett, MD

Articles

PET/CT finds footing in breast, cervical, and ovarian carcinoma

Anatomic, functional imaging collaborate in cancer detection