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Quantification of tumour 18 F-FDG uptake: Normalise to blood glucose or scale to liver uptake?

  • Nuclear Medicine
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Abstract

Purpose

To compare normalisation to blood glucose (BG) with scaling to hepatic uptake for quantification of tumour 18 F-FDG uptake using the brain as a surrogate for tumours.

Methods

Standardised uptake value (SUV) was measured over the liver, cerebellum, basal ganglia, and frontal cortex in 304 patients undergoing 18 F-FDG PET/CT. The relationship between brain FDG clearance and SUV was theoretically defined.

Results

Brain SUV decreased exponentially with BG, with similar constants between cerebellum, basal ganglia, and frontal cortex (0.099–0.119 mmol/l−1) and similar to values for tumours estimated from the literature. Liver SUV, however, correlated positively with BG. Brain-to-liver SUV ratio therefore showed an inverse correlation with BG, well-fitted with a hyperbolic function (R = 0.83), as theoretically predicted. Brain SUV normalised to BG (nSUV) displayed a nonlinear correlation with BG (R = 0.55); however, as theoretically predicted, brain nSUV/liver SUV showed almost no correlation with BG. Correction of brain SUV using BG raised to an exponential power of 0.099 mmol/l−1 also eliminated the correlation between brain SUV and BG.

Conclusion

Brain SUV continues to correlate with BG after normalisation to BG. Likewise, liver SUV is unsuitable as a reference for tumour FDG uptake. Brain SUV divided by liver SUV, however, shows minimal dependence on BG.

Key Points

FDG standard uptake value in tumours helps clinicians assess response to treatment.

SUV is influenced by blood glucose; normalisation to blood glucose is recommended.

An alternative approach is to scale tumour SUV to liver SUV.

The brain used as a tumour surrogate shows that neither approach is valid.

Applying both approaches, however, appropriately corrects for blood glucose.

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Acknowledgments

The scientific guarantor of this publication is Michael Peters. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in AJR 2014;203:643–8 and Eur J Radiol 2014;83:751–5. Methodology: retrospective, observational, performed at one institution.

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Correspondence to Georgia Keramida.

Appendix

Appendix

The EANM guidelines recommend normalisation of tumour SUV to blood glucose of 5 mmol/l. This presupposes a hyperbolic relationship (i.e., y = constant/x) between SUV and blood glucose.

MRGLU in tissues in which FDG is metabolically trapped is related to tissue FDG clearance rate (Zi) and blood glucose concentration (G), as follows [21]:

$$ {\mathrm{MR}}_{\mathrm{GLU}}=\mathrm{Z}\mathrm{i}\kern0.5em \times \kern0.5em \mathrm{G}\kern0.5em \times \kern0.5em \mathrm{L}\mathrm{C} $$
(1)

Where LC is lumped constant.

Rearranging Eq. 1 and ignoring LC,

$$ \mathrm{Z}\mathrm{i}=\kern0.5em {\mathrm{MR}}_{\mathrm{GLU}}/\mathrm{G} $$
(2)

Assuming MRGLU is constant, this indicates a hyperbolic relationship between Zi and G.

Tissue SUV (SUVi) is a surrogate for Zi but is not identical to it. It is related to Zi as follows.

$$ \mathrm{Z}\mathrm{i}\kern0.5em =\kern0.5em \mathrm{M}\left(\mathrm{t}\right)/ area\left(\mathrm{t}\right), $$
(3)

where M(t) and area(t) are respectively the quantity of FDG accumulated in the tissue and the area under the blood FDG time-concentration curve at time t (60 min in the current study).

Substituting for Zi in Eq. 1

$$ {\mathrm{MR}}_{\mathrm{GLU}}=\mathrm{M}\left(\mathrm{t}\right)/\mathrm{area}\left(\mathrm{t}\right)\kern0.5em \times \mathrm{G} $$
(4)
$$ \mathrm{Now}\kern0.5em \mathrm{SUVi}\kern0.5em =M(t)/\mathrm{V}\kern0.5em x\kern0.5em W/M(0), $$
(5)

where V is tissue volume, W is body weight and M(0) is administered activity.

Rearranging Eq. 5

$$ M(t) = \mathrm{SUVi}\ \mathrm{x}\ \mathrm{V}/\mathrm{W}\ \mathrm{x}\ \mathrm{M}(0) $$
(6)

Substituting for M(t) in Eq. 4 and rearranging,

$$ {\mathrm{MR}}_{\mathrm{GLU}}/\mathrm{V} = \mathrm{SUVi}\ \mathrm{x}\ \mathrm{M}(0)/\mathrm{W} \times \mathrm{G}/\mathrm{area}\left(\mathrm{t}\right) $$
(7)

For typical FDG blood clearance half-times of around 50 min from completion of early mixing (~10 min) [20], area(60 min) is approximately proportional to C(60 min), where C(t) is the blood concentration of FDG. For example, comparing clearance half-times of 69 and 50 min, the concentration and area ratios are 1.28 and 1.11, respectively, similar to the corresponding ratios for half-times of 50 and 39 min (1.26 and 1.11); i.e., same error.

So, substituting C(t) for area(t) in Eq. 7 and ignoring the proportionality constant,

$$ {\mathrm{MR}}_{\mathrm{GLU}}/\mathrm{V} = \mathrm{SUVi} \times \mathrm{M}(0)/\mathrm{W} \times \mathrm{G}/\mathrm{C}\left(\mathrm{t}\right) $$
(8)

Analogous to Eq. 5,

$$ \mathrm{left}\ \mathrm{ventricular}\ \mathrm{blood}\ \mathrm{S}\mathrm{U}\mathrm{V}\kern0.5em \left({\mathrm{SUV}}_{\mathrm{LV}}\right)\kern0.5em =\kern0.75em \mathrm{C}\left(\mathrm{t}\right) \times \mathrm{W}/\mathrm{M}(0) $$
(9)

Substituting for C(t) in Eq. 8,

$$ {\mathrm{MR}}_{\mathrm{GLU}}/\mathrm{V} = \mathrm{SUVi}/{\mathrm{SUV}}_{\mathrm{LV}} \times \mathrm{G} $$
(10)

Rearranging Eq. 10,

$$ \mathrm{SUVi}/{\mathrm{SUV}}_{\mathrm{LV}}=\kern0.5em {\mathrm{MR}}_{\mathrm{GLU}}/\mathrm{V}\kern0.5em \times \kern0.5em 1/\mathrm{G} $$
(11)

So SUVi/SUVLV, rather than SUVi, has a hyperbolic relationship with blood glucose and therefore more closely represents Zi. Because of the kinetics of FDG distribution between hepatocytes and blood, liver FDG concentration closely reflects blood FDG concentration [1316]. In Eq. 11, therefore, SUVLV can be replaced by SUVliver:

$$ \mathrm{SUVi}/{\mathrm{SUV}}_{\mathrm{liver}}=\kern0.5em {\mathrm{MR}}_{\mathrm{GLU}}/\mathrm{V}\times 1/\mathrm{G} $$
(12)

Alternatively, the relationship between SUVi and blood glucose can be regarded as exponential, i.e.,

$$ \mathrm{SUVi}\kern0.5em =\kern0.5em \mathrm{A}.{\mathrm{e}}^{\hbox{-} \mathrm{k}.\mathrm{G}} $$
(13)

The exponential constant k is the fractional decrease in SUVi per unit increase in blood glucose, and intuitively should be constant for tissues that metabolically trap FDG. Tissue MRGLU would then be reflected by A.

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Keramida, G., Dizdarevic, S., Bush, J. et al. Quantification of tumour 18 F-FDG uptake: Normalise to blood glucose or scale to liver uptake?. Eur Radiol 25, 2701–2708 (2015). https://doi.org/10.1007/s00330-015-3659-6

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  • DOI: https://doi.org/10.1007/s00330-015-3659-6

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