TY - JOUR T1 - Myocardial glucose suppression interferes with the detection of inflammatory cells with FDG-PET in a canine model of myocardial infarction JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 52 LP - 52 VL - 62 IS - supplement 1 AU - Benjamin Wilk AU - Haris Smailovic AU - Rebecca Sullivan AU - John Butler AU - Jane Sykes AU - Michael Kovacs AU - Gerald Wisenberg AU - Jonathan Thiessen AU - Frank Prato Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/52.abstract N2 - 52Introduction: Cardiovascular disease is the leading cause of death worldwide. Heart failure, specifically, is influenced to a major extent by disregulation of inflammation which occurs after a myocardial infarction (MI)[1]. MRI and extracellular volume (ECV) measurements have shown promise in detecting characteristics that can increase the risk of heart failure, including: infarct size, presence of hemorrhage and presence and size of an area of very low blood flow within the infarct called the region of microvascular obstruction (MO)[2]. What is needed is an imaging method that can distinguish between pro-inflammatory (neutrophils and M1 macrophages) and anti-inflammatory (M2 macrophages) cells as disregulation occurs when the pro-inflammatory phase is prolonged. It has been shown that FDG-PET can, in principle, distinguish between the pro- and anti-inflammatory cell types [3]; however, post-MI there are some problems including uptake of FDG in resting healthy myocardium which has to be suppressed so that the uptake of glucose by inflammatory cells can be distinguished from uptake in healthy myocardium. Myocyte glucose uptake suppression in the canine model can be achieved through a combination of fasting, the injection of heparin and the lipid infusion. However, it is not known if this suppression of myocyte uptake of FDG may also affect the degree of uptake of FDG by the inflammatory cells (macrophages). Here we report on our investigation of this potential limitation. We have evaluated the use of a prolonged constant infusion of FDG and Gd-DTPA instead of a bolus injection to penetrate the area of MO. This prolonged constant infusion also allows us to show the effect of suppression on uptake of FDG of inflammatory cells within the region of infarction, through tracking of the metabolic activity before during and after the infusion of agents to nominally suppress myocardial glucose uptake. Methods: Six canines were imaged with hybrid FDG PET and MRI using a Siemens Biograph mMR at baseline and 5 days post-MI when the pro-inflammatory response should be peaking. FDG and Gd-DTPA were infused for 150 minutes starting simultaneously with the dynamic PET acquisition. T1 maps were acquired every 10 minutes throughout the scan to calculate extracellular volume. Suppression was started at 40 minutes into the scan by heparin injection and a 50 min lipid infusion. Patlak modelling was done at three times during this constant infusion: 12-39 minutes (before suppression), 60 - 90 minutes (during suppression) and 120 - 150 minutes (after suppression). ECV was calculated at 40, 90 and 150 minutes. Results: No significant difference is seen in ECV measurements before, during and after suppression, although ECV is approximately twice as high in the infarcted tissue than the remote tissue. The metabolic rate of glucose (MRGlu) is significantly lower during and after suppression, both in the infarcted and remote tissue, though the effect is larger in remote tissue (see figure). Conclusions: These results are the first to show an effect of heparin and intralipid on the metabolic rate of glucose activity in the infarcted tissue, suggesting either an effect of suppression on macrophages or alternatively, the presence of a significant volume of viable myocytes in the infarcted region. This potential effect of suppression on inflammatory cells highlights the need for tracers that are not only specific for the presence of inflammation but whose uptake is not confounded by the metabolic state present not only at the time of injection, but during the period of imaging. [1] Frangogiannis, NG. (2014). Nat Rev Cardiol. 11(5): 255-265. [2] Kali A. (2016). Circulation Cardiovasc Imaging. 9(11): e004996. [3] Thackeray, J. (2017). SNMMI 2017. J Nucl Med. 58:302. ER -