LAUSR

Dear Sir, We read with interest the article recently published in EJNMMI by Salomon et al. [1] that described a negative relationship between hepatic steatosis and SUV, and recommended the use of SULmax rather than SUVmax as the comparator in the Deauville scoring (DS) system because it minimises the influence of body mass index (BMI). They found, nevertheless, that it made little difference to DS whether SULmax or SUVmax was used. It is stated (but only in the Abstract) that in their scoring system, SULmax was applied to the lymphoma. Provided lymphoma and liver are compared either on the basis of SUVor SUL, body weight will cancel out and remove any influence of BMI on DS. It makes no sense to compare an SULwith an SUV, or vice versa, so normalising any tumour to liver removes the need to choose between SUL and SUV, provided whichever one is used is applied to both tissues. In any event, in our view, the liver is just about the least appropriate tissue against which to normalise tumour SUV because of the opposing relationships that tumour and liver SUV respectively have with blood glucose level. The wellknown inverse relationship between tumour SUV and blood glucose [2] implies that tumours are insensitive to insulin. This opposing relationship with blood glucose makes the ratio of tumour-to-liver SUVexquisitely sensitive to blood glucose. Using brain, which is also insensitive to insulin [3], as a surrogate for tumour, we previously demonstrated a hyperbolic relationship between brain-to-liver SUV ratio and blood glucose. If lymphoma behaves like brain, then a similar hyperbolic relationship would exist for lymphoma. Liver and brain SUValso display opposing relationships with time from FDG injection. Time course of tissue activity depends on the ratio of tissue blood clearance of FDG (to phosphorylation) and tissue FDG distribution volume. This ratio is much higher for brain, and almost certainly also for tumours, than for liver [4]. Even at 60 min post-injection, about 50% of administered FDG is still in the circulation [4]. The positive relationship between liver SUV and blood glucose then arises because at 60 min about 75% of intrahepatic FDG is unphosphorylated and in rapid dynamic exchange with blood FDG [4, 5]. Because of competition for tissue uptake, blood FDG level increases with increasing blood glucose level [6]. The liver is sensitive to insulin [7] so increasing blood glucose level increases the intrahepatic concentration of phosphorylated FDG, accentuating the positive relationship between blood glucose and hepatic SUV, although this is probably less important than unphosphorylated FDG. The dependence of liver SUVon blood FDG concentration is well shown in Fig. 4 of the paper of Salomon et al. in which in (b) there is a prominent blood pool signal matching the high liver activity, in contrast to (a) in which there is lower liver activity and a much less prominent blood pool signal. The old literature even went as far as suggesting the use of the liver as a blood pool region in small animal dynamic FDG studies in which placement of ROI over left ventricular cavity or major artery was not considered feasible [8]. Mediastinum, which is also widely used as a comparator to derive the DS, is also predominantly blood pool, and therefore similarly unsuitable for quantification of FDG uptake in lymphoma. Theoretically, FDG is ‘shared’ around the body such that whole body SUV is unity. Regional SUV is influenced by many factors, including the tumour burden, which determines how much FDG is available for uptake elsewhere (likewise treatment-activated bone marrow). Paradoxically, therefore, a response to therapy with reduction of tumour burden could result in an increase in tumour SUV. Duration of patient fasting, even when blood glucose is normal, is probably also a factor as it affects insulin levels. As it is intuitively likely that lymphoma and brain respond similarly to all these factors, it * A. Michael Peters [email protected]