# Urine in PET studies

Urinary system consists of the kidneys, ureters, urinary bladder, and urethra. Excess water and water-soluble waste products of metabolism are mainly excreted into urine, and partly by sweating. The liver can process and excrete waste products into the bile and faeces. Water content of urine is >90%, and urea (∼10-20 g/mL) is the largest constituent of solids. Protein content is normally very low, <10 mg/dL. Specific gravity of urine depends on the water balance, but is normally 1.000-1.040 g/mL. Normal range for pH in urine sample is 4-8; pH >6 favours bacterial growth, and bacterial growth tends to increase urine pH.

## Urinary excretion

Urine is formed by renal filtration and tubular reabsorption and secretion. Adult humans produce daily ∼0.6-2.0 L urine, or 0.5-1.5 mL/(kg*h).

### Assessing urinary excretion

Urinary excretion is often measured from urine samples only, preferably by summing the radioactivities from early and late samples. After voiding, the amount of activity remaining in the bladder is relatively low (Jones et al., 1982).

Urine production rate (mL/min) can be estimated from the time between two voids and the volume of the second void, assuming that the residual volume in the bladder is the same for each void. The urine production rate and void volumes can be used to estimate the urine volume in the bladder at radioligand administration time (Dowd et al., 1991). For a radioligand that is excreted in its native form, we can assume that the activity of urine in the bladder (without voiding) has the same shape as the integral of the plasma time-activity curve. Urine activity curve could be represented with for example with three exponentials (Dowd et al., 1991):

Kinetics of radioactivity in the bladder can be used in deriving input function in small animal FDG PET studies (Wong et al., 2013).

### Clearance

Urinary clearance can be defined as (asymptomatic) activity in the urine (or bladder in the image) divided by the AUC of blood curve. Since the blood curve is used, the result is independent on radioligand uptake in the tissues.

Urinary clearance of [18F]fluoride has been used in rats to assess renal function noninvasively, with ROIs drawn on the heart cavity and urinary bladder. The results correlated with traditional GFR estimation methods, even with variable urine pH (Schnöckel et al., 2008). In humans, tubular reabsorption of [18F]F- is increased (renal clearance is reduced) with decreased urine flow (Park-Holohan et al, 2001), suggesting that the method may not be reliable for estimating renal function in humans.

### FDG

Mean percentages of FDG excreted into urine were 13±1% and 21±5% of injected dose 1 and 2 hours after FDG administration, respectively (Mejia et al., 1991). Urinary excretion of FDG is highly variable. Bach-Gansmo et al (2012) reported that excretion at mean latency time of 71 min was 2-20% of the injected dose, with an average of ∼10%. FDG excretion is somewhat higher in hydrated than dehydrated subjects, 17 versus 14% of injected dose 150 min after FDG administration (Moran et al., 1999). With strict water drinking and voiding schedule, two hours after FDG administration, 21±3% of injected dose was excreted into urine (Jones et al., 1982).

### Kidney function

Glomerular filtration rate (GFR) is used as an index of kidney function. Radioligands that are not protein bound in the blood, and are not reabsorbed, secreted, or metabolized in the renal tubular system, can be used to measure GFR; several PET tracers for this purpose have been introduced, including [68Ga]DOTA and [68Ga]EDTA. Error prone urinary collection can be avoided, when radioligand is only eliminated via glomerular filtration, and plasma and urinary clearances are thus equal; GFR can then be calculated from a few plasma samples. Alternatively, ROIs drawn on the bladder, ureters, and kidneys can be used (Hofman et al., 2015).

Radioligand and/or its radiometabolites are often excreted into urine, which leads to relatively high radiation dose to the urinary bladder and reduces the image quality in the pelvic region. In clinical imaging, especially in oncology, a whole-body scan is started only after a certain waiting period (late-scan); bladder voiding before the delayed scan can markedly improve the image quality and reduce the radiation dose to the patient and staff conducting the study. Bladder catheterization would be effective but impractical way to improve image quality.

### FDG

Early and frequent bladder voiding reduces radiation dose considerably (Hays & Segall, 1998). If the voiding time is changed from 2 h to 1 h after FDG administration, the radiation dose of bladder wall reduces by 50% (Jones et al., 1982). To minimize the dose to the bladder wall, the bladder should be as full as possible at the time of FDG administration (Dowd et al., 1991; Thomas et al., 1999). Hydration or administration of diuretics, such as furosemide, is recommended also in order to improve image contrast between urine and tumours in the pelvic area (Boellaard et al., 2015).

## References:

Garbarino S, Caviglia G, Sambuceti G, Benvenuto F, Piana M. A novel description of FDG excretion in the renal system: application to metformin-treated models. Phys Med Biol. 2014; 59(10): 2469-2484. doi: 10.1088/0031-9155/59/10/2469.

Schnöckel U, Reuter S, Stegger L, Schlatter E, Schäfers KP, Hermann S, Schober O, Gabriëls G, Schäfers M. Dynamic 18F-fluoride small animal PET to noninvasively assess renal function in rats. Eur J Nucl Med Mol Imaging 2008; 35: 2267-2274. doi: 10.1007/s00259-008-0878-y.

Ridley JW: Fundamentals of the Study of Urine and Body Fluids. Springer, 2018. doi: 10.1007/978-3-319-78417-5.

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Updated at: 2018-10-07
Created at: 2018-10-05
Written by: Vesa Oikonen