Standardized uptake value (SUV)

Standardized uptake value, SUV, (also referred to as the dose uptake ratio, DUR) is a widely used, robust PET quantifier, calculated simply as a ratio of tissue radioactivity concentration (for example in units [kBq/mL]) at time T, CPET(T), and administered dose (for example in units [MBq]) at the time of injection divided by body weight (usually in units [kg]).

Tissue radioactivity and dose must be decay corrected to the same time point. The divider of the equation represents the average radioactivity concentration (per weight) in the whole body, and thus the SUV equals regional-to-whole body ratio of radioactivity concentrations. If the above mentioned units are used, the unit of SUV will be [g/ml]. Obviously, the average SUV of the whole body is the same as the density of the body, that is ≲1.

Instead of the body weight, the administered dose may also be corrected by the lean body mass (LBM) (Tahari et al., 2014; Keramida et al., 2015a), or body surface area (BSA) (Kim et al., 1994; Shomburg et al., 1996). For FDG PET studies the SUVLBM (sometimes referred to as SUL) is recommended (Zasadny & Wahl, 1993; Tahari et al., 2014; Keramida et al., 2015a); since FDG uptake in adipose tissue is low, glucose uptake assessed as SUVBW would be overestimated in obese patients (Sugawara et al., 1999). The same issue applies to other hydrophilic radiopharmaceuticals, including [68Ga]PSMA-11 (Gafita et al., 2019).

Verbraecken et al (2006) review the different formulas for calculating the BSA. Tahari et al (2014) recommends using the LBM calculation formula, including body mass index (BMI), developed by Janmahasatian et al (2005) for men:

and for women:

On the other hand, using LBM may lead to underestimation, because adipose tissue is not completely inert. As a compromise between total body weight and lean body weight, the SUV in small animal obesity models have sometimes been calculated by adjusting body weight according to Kleiber laws (Drake et al., 2011; Lee et al., 2015).

Calculation of SUV does not require blood sampling or dynamic imaging. The imaging must take place at a late time point, and always at the same time point, if results are to be compared (Eckelman et al., 2000). If the kinetics of the radioligand in target tissue is irreversible, and approximately invariant shape of arterial input function can be assumed, then SUV and SUR can be corrected for another scan time with good accuracy; correction is based on full dynamic studies (van den Hoff et al., 2014).

In FDG studies SUV can be corrected for plasma glucose level, because glucose transporters may be saturated by glucose. SUV is multiplied by plasma glucose concentration / 5.0 (where 5.0 represents the population average of plasma glucose concentration). Increased plasma glucose concentration may introduce also regional changes in FDG uptake, resembling Alzheimer disease -like patterns in the brain (Ishibashi et al., 2015). The dependence of FDG SUV on the plasma glucose concentration is dependent on the tissue, and the correction method should be investigated (Thie, 2017). In a rat study, hyperglycemia and hyperinsulinemia led to marked decrease of FDG SUV in the tumour, brain, and gut, and slight SUV increase in the blood, kidney, and skeletal muscle (Wahl et al., 1992). For analysis of tumour data, a meta-analysis suggested that no intervention is needed if blood glucose concentration is lower than 11.1 mM (200 mg/dL) (Eskian et al., 2019). In hyperglycaemic patients, blood glucose level can be safely lowered with insulin prior to FDG PET (Pattison et al., 2019).

SUVmean, SUVmax, and SUVpeak

When regional radioactivity concentrations are converted to SUV units, the result is SUVmean (or simply SUV), representing the mean SUV of voxels inside the volume of interest (VOI).

Cancer treatment response is usually assessed with FDG PET by calculating the SUV on the highest image pixel in the tumour regions (SUVmax), because this provides lower inter-observer variability than the averaged SUVmean . Nahmias and Wahl (2008) reported that the use of SUVmax has worse reproducibility (3% ± 11%) than does the SUVmean value (1% ± 7%), and Burger et al (2012) confirmed that repeatability of SUVmean is superior to SUVmax. SUVmax is also affected by image reconstruction parameters, for example, point-spread-function (PSF) and time-of-flight (TOF) reconstruction provide higher SUVmax values (Rogasch et al., 2015).

SUVpeak is based on a spherical VOI having a volume of ~1 mL in a position that provides the maximal VOI average. It avoids the noise-induced bias of SUVmax, but is more prone to the partial volume effects (Lodge et al., 2012). Combination of SUVmax and SUVpeak (Lasnon et al., 2013) should become the standard approach in multi-centre FDG PET/CT studies (Boellaard, 2013).

Alternatively, metabolic tumour volume can be estimated using threshold or region growing techniques, and average SUV inside the region is reported as such or multiplied by tumour volume to calculate the total glycolytic volume, TGV (Boucek et al., 2008).

SUV drawbacks

SUV is vulnerable to several major sources of variability (Hamberg et al. 1994; Keyes 1995; Huang 2000; Laffon et al. 2008), and the application of SUV as a quantitative index should be discouraged. The only reason for its continuous usage is that dynamic imaging and blood sampling are not necessary.

Although SUV and Ki may correlate well over the patient population, they may provide even opposite conclusions regarding the progression of disease (Freedman et al., 2003). Image noise, poor resolution and ROI definition affect the SUV and may hamper their use, especially in multi-centre trials (Boellaard et al., 2004).

In oncological (multi-centre) studies variance in SUV may be reduced by dividing tumour SUVmax or SUVpeak by SUV in liver; result is often called SUV ratio (SUVR, SUR) or, specifically, tumour-to-liver ratio (TLR). Any calibration problems cancel out in this method, which essentially is the same as tissue-to-reference tissue ratio at a late time point. Tumour-to-blood ratio (TBR) at a late time point has been shown to correlate with metabolic rate of FDG in tumors (van den Hoff et al., 2013; Hofheinz et al., 2016). TBR corrects for the "sink effect" that occurs as the the result of increased tumour volume (Cysouw et al., 2020). It is the preferred method over tumour-to-liver ratio, especially if blood activity can be determined from the same PET image; then the possible issues in calibration are again avoided. If blood or liver activity cannot be determined from the PET image, then the single venous blood sample is relatively easy to obtain.

If blood curve has been measured, a simple but quantitative alternative to SUV is fractional uptake rate (FUR), which is an approximation to the Patlak slope Ki, but does not require dynamic PET scan. FUR and SUV are proportional, related by plasma clearance rate and a dimensionless initial distribution volume (Thie, 1995).

%ID/L

In animal studies, dissected tissue samples are weighted and radioactivity is measured. Radioactivity is divided by sample weight to calculate the concentration (Bq/g). With injected dose and animal weight the SUV could be calculated similarly as from PET data. However, in animal studies the animal weight is often not taken into account: radioactivity concentration is simply divided by injected dose and multiplied by 100, and outcome is percent of injected dose per gram of tissue (%i.d./g).

Similar calculation can be done to PET data. In PET image the radioactivity concentration is measured per tissue volume (Bq/mL) instead of mass, and therefore the outcome will be in units %i.d./mL or %i.d./L. If tissue density (g/mL) is known or assumed to be 1 g/mL, it can be converted to %i.d./g.


See also:


Literature

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RSNA. Standardized Uptake Value (SUV)

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Updated at: 2023-06-14
Created at: 2008-11-20
Written by: Vesa Oikonen