Combined PET-CT

Positron Emission Tomography (PET) is an imaging modality that captures the level of metabolic activity of different tissues. After a peripheral intravenous (IV) line is placed, patients are given an IV injection of 2-(18F) fluoro-2-deoxy-D-glucose (FDG) followed by imaging 60 minutes later. The degree of metabolic activity within nodules, masses, and lymph nodes correlates with the level of FDG uptake which is reported as a standardized uptake value (SUV). Numerous studies have demonstrated the accuracy of PET for the diagnosis of lung cancer in pulmonary nodules and masses(1-5) as well as for staging evaluation. (6-7) A meta-analysis performed by Gould (2001) reports the sensitivity and specificity of PET for the detection of malignancy to be 96.8% and 77.8%, respectively. (4) More recently, Fischer (2009) demonstrated that combined PET-CT improves the selection of patients with known or suspected lung cancer for surgical resection by decreasing the number of futile as well as total thoracotomies. (8) An earlier trial found similar benefits with PET imaging alone. (9)

Delayed PET imaging is also of interest. Malignant processes continue to increase FDG uptake over 1.5 to 5 hours. (10) Thus, an increase in the SUV of nodules, masses, or adenopathy over time may suggest a malignant etiology. (11-13)

It is important to realize that FDG uptake also occurs in inflammatory and infectious processes thereby limiting its ability to discriminate between these and malignant processes. Hara (2003) reported a mean SUV of 6.45 + 2.30 for 14 patients with tuberculosis while 97 untreated patients with lung cancer had a mean SUV of 5.29 + 2.72.14 This emphasizes the importance of obtaining tissue confirmation of malignancy for FDG-avid lesions.

False negatives can result from the limited spatial resolution of PET scanners affecting the accuracy of this test in subcentimeter pulmonary nodules as well as mediastinal or hilar adenopathy. (7) In addition, many bronchioloalveolar carcinomas and carcinoid tumors have been reported to be cold or to have low uptake on PET imaging. (15-19) Patients with poorly controlled diabetes mellitus or hyperglycemia are also more likely to have false negative studies as a result of the elevated levels of endogenous glucose competing for uptake with FDG.

Malignancies with low or negative PET signal appear to be associated with better prognoses. (20) As a corollary, the level of PET activity appears to correlate with prognosis (21) and the change in activity with chemotherapy correlates with histopathologic response. (22-23)

References

1. Sazon DA, Santiago SM, Soo Hoo GW, et al. Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer. Am J Respir Crit Care Med. Jan 1996;153(1):417-421.


2. Saunders CA, Dussek JE, O'Doherty MJ, Maisey MN. Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer. Ann Thorac Surg. Mar 1999;67(3):790-797.


3. Weber W, Young C, Abdel-Dayem HM, et al. Assessment of pulmonary lesions with 18F-fluorodeoxyglucose positron imaging using coincidence mode gamma cameras. J Nucl Med. Apr 1999;40(4):574-578.


4. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. Feb 21 2001;285(7):914-924.


5. Fletcher JW, Kymes SM, Gould M, et al. A comparison of the diagnostic accuracy of 18F-FDG PET and CT in the characterization of solitary pulmonary nodules. J Nucl Med. Feb 2008;49(2):179-185.


6. Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med. Jul 27 2000;343(4):254-261.


7. Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med. Dec 2 2003;139(11):879-892.


8. Fischer B, Lassen U, Mortensen J, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med. Jul 2 2009;361(1):32-39.


9. van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomized trial. Lancet. Apr 20 2002;359(9315):1388-1393.


10. Hamberg LM, Hunter GJ, Alpert NM, Choi NC, Babich JW, Fischman AJ. The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? J Nucl Med. Aug 1994;35(8):1308-1312.


11. Kubota K, Itoh M, Ozaki K, et al. Advantage of delayed whole-body FDG-PET imaging for tumour detection. Eur J Nucl Med. Jun 2001;28(6):696-703.


12. Matthies A, Hickeson M, Cuchiara A, Alavi A. Dual time point 18F-FDG PET for the evaluation of pulmonary nodules. J Nucl Med. Jul 2002;43(7):871-875.


13. Uesaka D, Demura Y, Ishizaki T, et al. Evaluation of dual-time-point 18F-FDG PET for staging in patients with lung cancer. J Nucl Med. Oct 2008;49(10):1606-1612.


14. Hara T, Kosaka N, Suzuki T, Kudo K, Niino H. Uptake rates of 18F-fluorodeoxyglucose and 11C-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Chest. Sep 2003;124(3):893-901.


15. Kim BT, Kim Y, Lee KS, et al. Localized form of bronchioloalveolar carcinoma: FDG PET findings. AJR Am J Roentgenol. Apr 1998;170(4):935-939.


16. Higashi K, Ueda Y, Seki H, et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med. Jun 1998;39(6):1016-1020.


17. Erasmus JJ, McAdams HP, Patz EF, Jr., Coleman RE, Ahuja V, Goodman PC. Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol. May 1998;170(5):1369-1373.


18. Heyneman LE, Patz EF. PET imaging in patients with bronchioloalveolar cell carcinoma. Lung Cancer. Dec 2002;38(3):261-266.


19. Marom EM, Sarvis S, Herndon JE, 2nd, Patz EF, Jr. T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET. Radiology. May 2002;223(2):453-459.


20. Cheran SK, Nielsen ND, Patz EF, Jr. False-negative findings for primary lung tumors on FDG positron emission tomography: staging and prognostic implications. AJR Am J Roentgenol. May 2004;182(5):1129-1132.


21. Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake values on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg. Jul 2005;130(1):151-159.


22. Hoekstra CJ, Stroobants SG, Smit EF, et al. Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncology Nov 20 2005;23(33):8362-8370.


23. Pottgen C, Levegrun S, Theegarten D, et al. Value of 18F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in non-small-cell lung cancer for prediction of pathologic response and times to relapse after neoadjuvant chemoradiotherapy. Clin Cancer Res. Jan 1 2006;12(1):97-106.