PET Scanning: Worth the Cost in Cancer? Not for All Cancers-It’s Not Reliable Enough Yet

OncologyOncology Vol 28 No 5
Volume 28
Issue 5

In order for a test to be reliable, it must be reproducible and minimize test-retest variability. Yet, as with many imaging tests, FDG-PET has variance in standard uptake value (SUV) calculations, and even if standardization could be achieved, there is the issue of treatment effects, which introduce additional complexities.

Positron emission tomography (PET) imaging is often used in the staging and follow-up of a variety of malignancies, including lymphoma, lung,[1-3] breast,[4] colon,[5] esophageal, gastric,[6] pancreatic, biliary, and gynecologic[7] cancers. For example, a quick search of the PubMed MeSH Database for the key words “positron emission tomography” and “pancreas” returns 140 citations. While there are benefits to 18-fluorodeoxyglucose PET (FDG-PET) imaging in some of these tumors, pancreatic ductal adenocarcinoma (PDAC) can be taken as a fairly typical example of a tumor in which both the strengths and weaknesses of PET are evident. At our center, using FDG-PET to identify the primary PDAC or to differentiate focal pancreatitis from PDAC has been problematic. The trouble lies in the frequent inability of PET to reliably identify early PDAC,[8] which would portend a good prognosis. While recent work has shown the value of FDG-PET in identifying metastatic disease, its weakness in identifying nearby metastatic lymph nodes has also been shown, supporting our experience.[9] A recent meta-analysis of FDG-PET in PDAC[10] that comprised 30 studies and 1,582 subjects showed the failure of FDG-PET as a tool for local staging.

In order for a test to be reliable, it must be reproducible and minimize test-retest variability. Yet, as with many imaging tests, FDG-PET has variance in standard uptake value (SUV) calculations,[11,12] as shown by a recent study of the use of FDG-PET at a single institution.[13] It should be noted, however, that some centers are studying methods that may reduce variability, such as semiautomatic PET analysis[14] or automated FDG dose administration.[15]

Yet even if standardization could be achieved, there is the issue of treatment effects, which introduce additional complexities. For example, after a patient receives neoadjuvant chemoradiation for locally advanced PDAC, the inflammation from radiation can be difficult, if not impossible, to distinguish from malignancy. Semiautomatic techniques may help to show results similar to those found in small samples of subjects in whom malignancy was distinguishable from radiation changes.[16] Of course, histopathology is not held to such a standard either, since monitoring response to therapy via biopsy is not performed.

In settings where FDG-PET as currently used has limitations, and where biopsy is not an option, perhaps the solution is to develop and utilize targeted molecular agents. Glycolysis may be too nonspecific to be a useful biomarker. Instead, a focus on agents such as [18F]-fluoro-azomycinarabino-furanoside ([18F]FAZA), which may be a biomarker of hypoxia and which has been studied in human subjects, may prove fruitful.[17] Preclinical and clinical targeted molecular imaging agents-such as integrin αvβ6,[18] carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6),[19] or human sodium iodide symporter gene (hNIS)[20]-are also under study as targets in pancreatic cancer imaging. As such molecular imaging agents and drugs become targeted to specific malignancies or to markers derived from an individual patient’s cancer, the nonspecific nature of FDG-PET imaging may be able to be avoided.

Financial Disclosure:The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.


1. Søgaard R, Fischer BM, Mortensen J, et al. The optimality of different strategies for supplemental staging of non-small-cell lung cancer: a health economic decision analysis. Value Health. 2013;16:57-65.

2. Wu Y, Li P, Zhang H, et al. Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non-small-cell lung cancer patients. Int J Cancer. 2013;132:E37-47.

3. Uehara H, Tsutani Y, Okumura S, et al. Prognostic role of positron emission tomography and high-resolution computed tomography in clinical stage IA lung adenocarcinoma. Ann Thorac Surg. 2013;96:1958-65.

4. Andrade WP, Lima EN, Osório CA, et al. Can FDG-PET/CT predict early response to neoadjuvant chemotherapy in breast cancer? Eur J Surg Oncol. 2013;39:1358-63.

5. Arredondo J, Pastor C, Baixauli J, et al. Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer. Colorectal Dis. 2013;15:552-7.

6. Smyth E, Schöder H, Strong VE, et al. A prospective evaluation of the utility of 2-deoxy-2-[18 F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. Cancer. 2012;118:5481-8.

7. Fruscio R, Sina F, Dolci C, et al. Preoperative 18F-FDG PET/CT in the management of advanced epithelial ovarian cancer. Gynecol Oncol. 2013;131:689-93.

8. Matsumoto I, Shirakawa S, Shinzeki M, et al. 18-Fluorodeoxyglucose positron emission tomography does not aid in diagnosis of pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2013;11:712-8.

9. Asagi A, Ohta K, Nasu J, et al. Utility of contrast-enhanced FDG-PET/CT in the clinical management of pancreatic cancer: impact on diagnosis, staging, evaluation of treatment response, and detection of recurrence. Pancreas. 2013;42:11-9.

10. Wang Z, Chen JQ, Liu JL, et al. FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: a meta-analysis. World J Gastroenterol. 2013;19:4808-17.

11. Jacene HA, Leboulleux S, Baba S, et al. Assessment of interobserver reproducibility in quantitative 18F-FDG PET and CT measurements of tumor response to therapy. J Nucl Med. 2009;50:1760-9.

12. Fahey FH, Kinahan PE, Doot RK, et al. Variability in PET quantitation within a multicenter consortium. Med Phys. 2010;37:3660-6.

13. Kumar V, Nath K, Berman CG, et al. Variance of SUVs for FDG-PET/CT is greater in clinical practice than under ideal study settings. Clin Nucl Med. 2013;38:175-82.

14. Fox JJ, Autran-Blanc E, Morris MJ, et al. Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT. J Nucl Med. 2011;52:1727-32.

15. O’Doherty J, Woods E, Modde L, Mackewn J. Validation of an automated dose-dispensing system for 18F-FDG administrations and associated reduction in operator extremity dose. Nucl Med Commun. 2014;35:151-9.

16. Kittaka H, Takahashi H, Ohigashi H, et al. Role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in predicting the pathologic response to preoperative chemoradiation therapy in patients with resectable T3 pancreatic cancer. World J Surg. 2013;37:169-78.

17. Nascente CM, Dhani NC, Vines D, et al. Clinical characterization of hypoxia in pancreatic ductal adenocarcinoma (PDAC) by 18F-FAZA PET and pimonidazole. J Clin Oncol. 2013;31(Suppl):abstr 4049.

18. Hackel BJ, Kimura RH, Miao Z, et al. 18F-fluorobenzoate-labeled cystine knot peptides for PET imaging of integrin αvβ6. J Nucl Med. 2013;54:1101-5.

19. Niu G, Murad YM, Gao H, et al. Molecular targeting of CEACAM6 using antibody probes of different sizes. J Control Release. 2012;161:18-24.

20. Haddad D, Zanzonico PB, Carlin S, et al. A vaccinia virus encoding the human sodium iodide symporter facilitates long-term image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer. J Nucl Med. 2012;53:1933-42.

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