Effect of furosemide administration before F-18 fluorodeoxyglucose positron emission tomography/computed tomography on urine radioactivity and detection of uterine cervical cancer
1Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
2University of Milan, Milan, Italy
[Received: 24 III 2014; Accepted: 7 VII 2014]
BACKGROUND: In evaluating uterine cervical cancer with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), there may be overlap between the FDG activity at tumor sites and nonspecific radioactivity in the urine. We evaluated the efficacy of furosemide premedication with routine hydration to obtain better contrast and less overlap between cervical cancer and the urinary bladder.
MATERIAL AND METHODS: We retrospectively evaluated 166 patients who had primary or relapsed cervical cancer and underwent FDG PET/CT scanning with (133 patients) or without (33 patients) furosemide premedication (10 mg intravenous, slowly injected 30 min before the scan). We calculated bladder and tumor maximum and median standardized uptake value (SUVmax and SUVmed), and overlap between tumor and urinary activity was detected visually.
RESULTS: Overlap between urinary and tumor radioactivity was observed in 8 of 133 scans (6%) in patients who receive furosemide and in 3 of 33 scans (9%) in patients who did not receive furosemide. The SUVmax and SUVmed for the bladder were significantly lower in patients who were pretreated with furosemide (SUVmax, 6.3; SUVmed, 4.6) than patients who were not pretreated with furosemide (SUVmax, 8.8 [P ≤ 0.008]; SUVmed, 6.5 [P < 0.002]). The tumor SUVmax and SUVmed were similar between the patient groups.
CONCLUSION: Furosemide premedication before FDG PET/CT scanning may enable improved evaluation of activity and extension of cervical cancer.
KEY words: gynecologic oncology, cervix, imaging, diuretic, bladder
Nuclear Med Rev 2014; 17, 2: 83–86
Patients who have early cervical cancer can be treated with surgery or radiotherapy, but women who have more advanced cervical tumors that are metastatic to lymph nodes or pelvic tissues are treated usually with a combination of external beam radiotherapy and intracavitary brachytherapy. Evaluation with positron emission tomography/computed tomography (PET/CT) with the glucose analogue 18F-fluorodeoxyglucose (FDG) may facilitate tumor detection, staging, restaging after radical therapy, prognostic assessment, and radiotherapy planning [1–4].
The major source of uncertainty in the interpretation of PET/CT images is the anatomic position of the uterine cervix contiguous with the urinary bladder. Unlike glucose, FDG is not completely reabsorbed in the kidneys, and a variable amount of radioactivity may be found in the urinary tract after FDG injection. Therefore, there may be overlap between the FDG activity at tumor sites and nonspecific radioactivity in the urine. In 15 PET/CT centers, routine bladder catheterization usually is not performed before scanning . An alternative noninvasive way to decrease urine radioactivity is highly desirable.
Better contrast between tumor FDG uptake and urine radioactivity may be achieved by decreasing urine radioactivity with standardized patient hydration protocols or the administration of diuretic drugs before PET/CT scanning [6–7]. The European Association of Nuclear Medicine guidelines suggest hydration and diuretic administration during the investigation of small pelvic tumors .
We hypothesized that the diuretic furosemide may improve contrast between cervical cancer and the urinary bladder during PET/CT scanning. The purpose of the present study was to evaluate the efficacy of using furosemide with routine hydration to obtain better contrast and less overlap between cervical cancer and the urinary bladder.
Materials and methods
We retrospectively evaluated 166 patients who had primary or relapsed cervical cancer and who underwent FDG PET/CT scan at our center between December 2011 and November 2012. The scans were performed in accordance with current guidelines including intravenous injection of 18F-FDG (185 to 444 MBq) at 1 hour before image acquisition . The PET/CT scan was performed with 2 scanners (72 patients: Philips Gemini GXL16 scanner, Philips Healthcare, Andover, MA, USA; 94 patients: Siemens Biograph mCT128 scanner, Siemens, Malvern, PA, USA). The cross-calibration process was performed on a regular basis to ensure measurement stability between different scanners.
All patients were routinely instructed to drink ≥ 1 L of water within 2 hours before the examination and to void just before image acquisition. Patients were divided into 2 groups: patients who received premedication with furosemide (10 mg intravenous, slowly injected 30 min before the scan; 133 patients [80%]), and patients who did not receive furosemide because of a history of furosemide hypersensitivity, kidney stones, or renal colic (33 patients [20%]). No patient who was treated with furosemide had adverse events from diuretic administration. The maximum and median standardized uptake value (SUVmax and SUVmed) for the bladder and tumor were determined for each patient in both groups by manually drawing the free region of interest. Visual analysis was performed independently by 2 nuclear medicine specialists with software (Syngovia v.22.214.171.124, Siemens AG, Munich, Germany) to identify patients who had overlap between urinary and tumor activity.
Data analysis was performed with statistical software (STATISTICA v10.0, StatSoft, Tulsa, OK, USA). Normality of distribution was tested with Shapiro-Wilk test for SUVmax and SUVmed for the bladder and tumor for both patient groups; only the SUVmax and SUVmed for the tumor in patients who received furosemide were normally distributed. The basic statistics such as median, minimum, maximum, and interquartile range were calculated for each of the considered variables. The Mann-Whitney test was used for comparisons between the groups, because the groups were unrelated, the data were quantitative, and the data lacked normality. The primary outcome of the study was to compare the SUVmax and SUVmed for the bladder and tumor between the 2 patient groups. The null hypothesis assumed that the median values of these variables were equal. Statistical significance was defined by P < 0.05.
Overlap between urine and tumor radioactivity was observed in 8 of 133 scans (6%) in patients who received furosemide and in 3 of 33 scans (9%) in patients who did not receive furosemide (Figure 1 and 2). The bladder SUVmax and SUVmed were significantly lower in patients who were pretreated than in those who were not pretreated with furosemide (Table 1). The tumor SUVmax and SUVmed were similar between the patient groups (Table 1).
Table 1. Standardized uptake values from 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans in patients who had cervical cancer*
|Parameter||With furosemide||Without furosemide||P ≤ †|
|Median||(Minimum to maximum)||[Interquartile range]||Median||(Minimum to maximum)||[Interquartile range]|
The present result showed that SUV and SUV of the bladder, but not tumor, were significantly lower in patients who were pretreated than in those who were not pretreated with furosemide (Table 1). This suggests that pretreatment with furosemide may be helpful in minimizing overlap between the FDG activity at tumor sites and nonspecific radioactivity in the urine.
Nonspecific accumulation of FDG in the urinary tract may interfere with the visualization of pelvic and retroperitoneal abnormalities in a PET/CT scan. In the current literature, difficulties in images interpretation were reported in a significant percentage of patients, most frequently patients who had colorectal or ovarian cancers [9, 10]. This is an important issue, especially for patients with pelvic malignancies who are referred for PET/CT scan for radiotherapy planning. Bladder catheterization is effective but it is invasive and may cause urinary tract infection . In addition, bladder catheterization is time-consuming and difficult in clinical settings that have tightly scheduled examinations. Studies about the efficacy of furosemide premedication before PET/CT scanning have been performed for abdominal, bladder, and colorectal cancers, but only occasionally for cervical cancer [10–17].
The timing of diuretic injection is an important issue in order to obtain an optimal distinction between tumor and bladder . In our experience, most patients had difficulties in holding back urination for > 30 minutes after furosemide intravenous injection.
Statistical analysis of tumor activity showed no difference between patients who had or did not have furosemide premedication (Table 1). The significantly lower bladder radioactivity for patients who received furosemide pretreatment (Table 1) is evidence that increased urine production effectively reduce tracer concentration in the urinary tract. These data correlate with a higher ratio of overlap between urine and tumor images on the PET/CT scan in patients who did not receive furosemide that can hinder the delineation of tumor borders. This is important for the use of PET/CT scanning in planning cervical cancer radiotherapy. Adaptive radiotherapy strategies have been proposed to minimize the effect of possible changes in cervix position because varied bladder volumes may cause displacement of pelvic organs. It is possible to measure cervical displacement by comparing pretreatment CT scans with full and empty bladder [18, 19]. Modulated adaptive radiotherapy may be coupled with furosemide premedication to improve the quality of PET/CT images and accurately measure cervical displacement.
Table 2. Overlap between urinary and tumor radioactivity in patients with and without furosemide premedication
|Group||Number of patients||Patient with overlap (%)|
|With furosemide premedication||133||8 (6%)|
|Without furosemide premedication||33||3 (9%)|
The findings in this report are subject to at least two limitations. First, the sample size of control group is relatively small. Furthermore, comparison with a control group of catheterized patients was not carried out.
In summary, the present study shows that a combination of hydration and furosemide premedication may enable better evaluation of cervical cancer anatomy on PET/CT imaging. The present protocol potentially may be used in planning adaptive radiotherapy.
1. Amit A., Person O., Keidar Z. FDG PET/CT in monitoring response to treatment in gynecological malignancies. Curr Opin Obstet Gynecol 2013; 25: 17–22.
2. Petsuksiri J., Jaishuen A., Pattaranutaporn P., Chansilpa Y. Advanced imaging applications for locally advanced cervical cancer. Asian Pac J Cancer Prev 2012; 13: 1713–1718.
3. Klopp A.H., Eifel P.J. Biological predictors of cervical cancer response to radiation therapy. Semin Radiat Oncol 2012; 22: 143–150.
4. Kitajima K., Murakami K., Kaji Y., Sakamoto S., Sugimura K. Established, emerging and future applications of FDG-PET/CT in the uterine cancer. Clin Radiol 2011; 66: 297–307.
5. Graham M.M., Badawi R.D., Wahl R.L. Variations in PET/CT methodology for oncologic imaging at U.S. academic medical centers: an imaging response assessment team survey. J Nucl Med 2011; 52: 311–317.
6. Ceriani L., Suriano S., Ruberto T., Giovanella L. Could different hydration protocols affect the quality of 18F-FDG PET/CT images? J Nucl Med Technol 2011; 39: 77–82.
7. Diehl M., Manolopoulou M., Risse J. et al. Urinary fluorine-18 fluorodeoxyglucose excretion with and without intravenous application of furosemide. Acta Med Austriaca 2004; 31: 76–78.
8. Boellaard R., O’Doherty M.J., Weber W.A. et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 2010; 37: 181–200.
9. Yildirim-Poyraz N., Ozdemir E., Uzun B., Turkolmez S.. Dual phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography with forced diuresis in diagnostic imaging evaluation of bladder cancer. Rev Esp Med Nucl Imagen Mol 2013; 32: 214–221.
10. Miraldi F., Vesselle H., Faulhaber P.F., Adler L.P. Leisure GP Elimination of artifactual accumulation of FDG in PET imaging of colorectal cancer. Clin Nucl Med 1998; 23: 3–7.
11. Vesselle H.J., Miraldi F.D. FDG PET of the retroperitoneum: normal anatomy, variants, pathologic conditions, and strategies to avoid diagnostic pitfalls. Radiographics 1998; 18: 805–823.
12. Kamel E.M., Jichlinski P., Prior J.O. et al. Forced diuresis improves the diagnostic accuracy of 18F-FDG PET in abdominopelvic malignancies. J Nucl Med 2006; 47: 1803–1807.
13. Nair N., Basu S. Selected cases demonstrating the value of furosemide-primed 18F-FDG PET in identifying adrenal involvement. J Nucl Med Technol 2005; 33: 166–171.
14. Chen Y.W., Huang M.Y., Hou P.N., Chang C.C., Lee C.S., Lian S.L. FDG PET/CT delayed diuretic imaging technique for differentiating invasive pelvic cancer. Clin Nucl Med 2009; 34: 233–235.
15. Anjos D.A., Etchebehere E.C., Ramos C.D., Santos A.O., Albertotti C., Camargo E.E. 18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer. J Nucl Med 2007 May; 48: 764–770.
16. Nayak B., Dogra P.N., Naswa N., Kumar R. Diuretic. 18F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique. Eur J Nucl Med Mol Imaging 2013; 40: 386–393.
17. Nijjar S., Patterson J., Ducharme J., Leslie W.D., Demeter S.J. The effect of furosemide dose timing on bladder activity in oncology imaging with 18F-fluorodeoxyglucose PET/CT Nucl Med Commun 2010; 31: 167–172.
18. Bondar M.L., Hoogeman M.S., Mens J.W. et al. Individualized nonadaptive and online-adaptive intensity-modulated radiotherapy treatment strategies for cervical cancer patients based on pretreatment acquired variable bladder filling computed tomography scans. Int J Radiat Oncol Biol Phys 2012; 83: 1617–1623.
19. Rijkhorst E.J., Lakeman A., Nijkamp J. et al. Strategies for online organ motion correction for intensity-modulated radiotherapy of prostate cancer: prostate, rectum, and bladder dose effects. Int J Radiat Oncol Biol Phys 2009; 75: 1254–1260.
Andrea d’Amico, MD, PhD
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
Phone: (+48) 601 498 365