Research Article: Suppression of 18F-FDG signal in the bladder on small animal PET-CT

Date Published: October 17, 2018

Publisher: Public Library of Science

Author(s): Lorena Cussó, Manuel Desco, Pradeep K. Garg.

http://doi.org/10.1371/journal.pone.0205610

Abstract

Retention of 2-deoxy-2-[18F]fluoro-D-glucose 18F-FDG in the bladder causes more problems in small animal research than in human research owing to the smaller size of the subject. Catheterization has been proposed to reduce bladder spillover both in human studies and in small animal research. Noninvasive alternatives such as hydration plus furosemide also seem to be a promising pre-imaging strategy for decreasing bladder spillover. Our main goal was to measure the effects of the combination of furosemide and hydration for reducing bladder signal directly on mouse bowel 18F-FDG-PET images.

Nine mice were divided into two groups: the control group (C, n = 4) and the treatment group (n = 5). The clearance protocol combines hyperhydration and a single furosemide dose during the 18F-FDG uptake period. Two images were acquired on different days in treated mice to evaluate two different furosemide doses (low dose, LD, 3.5 mg/kg; and high dose, HD, 7 mg/kg). A region of interest was drawn on each computed tomography image (bladder, kidneys, liver, muscle, and bone marrow). To quantify bladder spillover, two different areas of the colon were selected.

A remarkable reduction in bladder spillover was achieved on 18F-FDG -PET in both groups. Our imaging findings were quantified, and both furosemide doses induced a decrease in mean standard uptake values (SUVmean) compared with the controls (LD 1.46 ± 0.54 and HD 1.05 ± 0.29; controls: 8.90 ± 3.4 [p-value < 0.05]). We validated a non-invasive, easy, and harmless pre-imaging alternative for decreasing 18F-FDG bladder spillover. Our study shows the effect of furosemide on bladder spillover directly on 18F-FDG-PET images by measuring SUVmean in the bladder, colon, liver, muscle, and bone marrow.

Partial Text

Clinical and preclinical applications of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) are increasingly used in a wide variety of disciplines such as oncology [1], cardiology [2, 3], neuroscience [4], and inflammatory and infectious diseases [5, 6]. Although unspecific uptake of 18F-FDG results in the well-known problem of detectability in several applications [7, 8], accumulation of urine also constitutes a relevant limitation of this radiotracer [9]. The accumulation mechanism depends on the fluorine atom in the molecule, which reduces the affinity of 18F-FDG for sodium-glucose linked transporter 1 on the proximal tubules of the nephron, thus decreasing reabsorption [10, 11] and, consequently, increasing elimination of 18F-FDG from urine. The accumulation of activity in the bladder leads to spillover, which may hamper visualization of neighboring lesions such as gynecological cancers [12], bladder wall malignances [13], and inflammatory bowel diseases (IBD) [5].

All mice were housed in cages under the same conditions (ad libitum access to food and water, with 12 h of light and 12 h of darkness).

Fig 2A shows examples of PET-CT images from each group. 18F-FDG-PET activity in the bladder was markedly reduced in both treated groups compared with the control mice. Our visual findings were quantified, and both furosemide doses induced a decrease in bladder SUVmean compared with the controls (LD 1.46 ± 0.54 and HD, 1.05 ± 0.27; controls, 8.90 ± 3.4 [p < 0.05]). Total bladder radioactivity counts also decreased with both furosemide doses (LD 1.49 x 105 ± 4.92 x 104 and HD, 7.40 x 104 ± 3.19 x 104) compared with controls (2.89 x 105 ± 4.28 x 104, [p < 0.05]). In addition, a larger variability was observed in the control group (3.4 vs. 0.54 in LD and 0.29 in HD; [p = 0.012]), coefficient of variation is higher in controls (38.2%) compared with HD (26.0%). The bladder clearance protocol also enabled a clear increase in bladder volume in treated animals compared with the control group, although the difference was not statistically significant (Fig 2C). In this work we assess a non-invasive, easy, and harmless pre-imaging procedure to decrease accumulation of 18F-FDG in the bladder. This clearance protocol combines hyperhydration with a single furosemide dose during the 18F-FDG uptake period. Our study quantifies the effect on 18F-FDG-PET images by measuring the SUVmean of the bladder bone marrow, liver, muscle, small intestine and colon in order to assess bladder spillover.   Source: http://doi.org/10.1371/journal.pone.0205610

 

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