The heart consumes more energy than any other organ in order to maintain its contractile performance.1 The healthy myocardium possesses the superb ability to utilize a wide variety of substrates including: free fatty acids, glucose, lactate, pyruvate, ketone bodies, and amino acids as energy sources, which makes it possible for it to function as a constant pump. In the healthy adult myocardium, free fatty acids are the major energy source; however, under certain conditions, such as the postprandial state when glucose is more available, the heart is capable of switching to a glucose-predominant substrate utilization pattern.2,3 During ischemia, when there is reduced oxygen available to the tissue, the heart must use anaerobic glycolysis for ATP and energy production. As such, glucose becomes the primary substrate for ischemic myocardium. 18F-fluorodeoxyglucose (FDG) is a glucose analog whose uptake parallels glucose and, therefore, can be used to reflect glucose utilization and the metabolic state of the myocardium. Viable myocardium that is ischemic or hibernating will take up glucose and thus FDG. Likewise normal myocardium (which is, of course, also viable) in the postprandial state will take up glucose and as such FDG.
As a metabolic viability test, cardiac PET imaging with FDG can assess the myocardium in either a fasting or a glucose-loaded state. A fasting protocol is preferred when one wants to suppress FDG uptake in normal tissue, as in the detection of inflammatory or infectious diseases, including: cardiac sarcoidosis, vasculitis, and infection of intravascular devices, pacemakers, and catheters. The fasting protocol is useful to suppress physiological myocardial FDG uptake, making it easier to distinguish between physiological and pathological FDG uptake (see Chapter 14 for discussion of preparation for FDG inflammation imaging).
In contrast, a glucose load protocol is selected for assessing myocardial viability in order to enhance FDG (glucose) uptake in the viable myocardium (both normal and ischemic/hibernating tissue). The most common protocol for glucose loading is with an oral load of 25–100 g. The glucose load induces a rapid increase in insulin secretion from β(beta)-cells of the pancreas, which enhances FDG uptake in the viable myocardium through the glucose transporter 4 (GLUT-4).4 However, oral glucose loading may not be as effective in patients with impaired glucose tolerance or diabetes because of the impaired response of the cells (including myocardial cells) to insulin stimulation as a result of insulin resistance, as well as a decrease in glucose transporter activity and reduction in transport rates owing to pretranslational suppression of GLUT-4 gene expression5 or their limited ability to produce endogenous insulin. Thus, the use of insulin along with close monitoring of blood glucose levels is used (routinely in some sites) to improve image quality in patients with diabetes or glucose intolerance.
In this chapter, we focus on FDG PET viability imaging with the glucose load protocol in patients with or without diabetes mellitus.
It is important to choose the right protocol for the right patient (either oral glucose load, intravenous insulin injections after oral glucose load, or an euglycemic-hyperinsulinemic clamp) in order to obtain optimal cardiac FDG PET images. The presence of diabetes mellitus can substantially affect the assessment of myocardial viability using FDG PET.6 In patients with diabetes, the myocardium-to-background ratio can be decreased compared with patients who do not have diabetes. This can be explained by lower myocardial glucose (and FDG) uptake and higher plasma glucose (and FDG) levels. Therefore, the status of glucose tolerance should be known prior to the scan, if at all possible. Diabetes can be diagnosed based on hemoglobin A1c (Hb A1C) criteria or plasma glucose criteria; fasting plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral glucose tolerance test (OGTT).7,8
The ASNC guidelines and University of Ottawa Heart Institute (UOHI) protocols are shown in Tables 10-1 and 10-2 and Appendices 10-1, 10-2, 10-3, respectively.9
Procedure | Steps for standardization | Technique |
---|---|---|
Fasting period | Step 1: Fast patient | |
*6-12 hours <6 hours Step 2: Check blood glucose (BG) and the glucose load (choose one of the following 3 options) | Preferred Suboptimal | |
Oral glucose load | Option 1: Oral glucose loading | |
IF:fasting BG <~250 mg/dL (13.9 mmol/L) THEN: (1) oral glucose load: typically 25–100 g orally (see Table 10-2) (2) monitor BG (see Table 10-2) IF: fasting BG >~250 mg/dL(13.9 mmol/L) THEN: see Table 10-2 | Standard
Standard | |
IV protocol | Option 2: Dextrose IV infusion | Optional |
(see ASNC/SNMMI Guidelines for details) | ||
Acipimox | Option 3: Acipimox | |
Acipimox, 250 mg orally not available in the United States | ||
18F-FDG injection | Step 3: Administer 18F-FDG | |
Time: Dependent on which option was selected Standard IV administration of 18F-FDG | ||
Begin PET imaging | 0-90 minutes post 18F-FDG injection (45–60 min postinjection for standard static imaging) |
BG at 45–60 min after administration | Restorative measure | Technique |
---|---|---|
130–140 mg/dL (7.22–7.78 mmol/L) | 1 U regular insulin IV | Standard |
140–160 mg/dL (7.78–8.89 mmol/L) | 2 U regular insulin IV | |
160–180 mg/dL (8.89–10 mmol/L) | 3 U regular insulin IV | |
180–200 mg/dL (10–11.11 mmol/L) | 5 U regular insulin IV | |
>200 mg/dL (>11.11 mmol/L) | Notify physician |
After at least 6 hours of fasting, an oral load of 25–100 g glucose is given.
At UOHI, the dosage of glucose is based on the baseline blood glucose (BG) level, measured by a glucometer. If BG is <90 mg/dL (5 mmol/L), 50 g of glucose is orally administered (see Appendix 10-1). If BG is 90–125 mg/dL (5.1–6.9 mmol/L), 25 g of glucose is given.
When BG is greater than 126 mg/dL (>7 mmol/L), the value is considered to be in the diabetic range of glucose intolerance (although BG measurement by a glucometer cannot be used for the diagnosis of diabetes). In such a situation, 25 g of oral glucose load along with 1–2 U of regular insulin is administered intravenously.
We typically administer 1–2 U of regular insulin when BG is 126–180 mg/dL (7–10 mmol/L). The dose of regular insulin is determined based on the patient’s body weight. Lean patients tend to develop hypoglycemia after insulin administration, thus walking is an alternative choice to decrease BG used at some institutions.
Blood glucose is measured 20 minutes after the insulin administration in order to identify hypoglycemia and to determine whether walking or the need for more insulin is necessary. When BG is greater than 181 mg/dL (>10 mmol/L), our team discusses whether administration of a larger dose of regular insulin or a switch to the euglycemic-hyperinsulinemic clamp is the best choice for a given patient. One hour postglucose load and insulin (if applicable), we recheck the BG to determine if this has achieved the optimal range (100–140 mg/dL = 5.55–7.77 mmol/L). When the BG is less than 144 mg/dL (<8 mmol/L), we proceed with FDG injection. When the BG is equal or greater than 144 mg/dL (>8 mmol/L), we use supplemental insulin (see Appendix 10-1). FDG is administered 1 hour postglucose load and insulin (if applicable). FDG can be given at the same time as supplemental insulin, if required. We recheck BG after 30 minutes if supplemental insulin has been given.