Myocardial uptake of F-18-fluorodeoxyglucose in whole body positron emission tomography studies.

PURPOSE: The objective of this study was to correlate the degree of myocardial fluorodeoxyglucose (FDG) uptake in routine oncology positron emission tomography (PET) studies with fasting blood sugar level (FBSL), fasting period (FP) and age of the patient.
MATERIALS AND METHODS: Ninety-one patients (62 males and 29 females, age range: 7-78 years) with malignant diseases were included in the study. Whole body FDF-PET study was carried out after 1 h of intravenous injection of 296-370 MBq (8-10 mCi) F-18 FDG. Images were interpreted visually and patients were classified into four grades of myocardial uptake: No myocardial uptake = Grade 0; mild uptake = Grade 1; moderate uptake = Grade 2; and Marked uptake = Grade 3. Quantitative analysis was done by calculating Standardized uptake value (SUVmax). Age, FBSL and FP were recorded.
RESULTS: Thirty-seven (41%) patients showed no uptake in myocardium (Gr-0). Mean FP, FBSL and age was 14 h, 94.19 mg% and 44.3 years respectively. Eleven (12%) cases were rated as Grade 1, 27 (30%) as Grade 2 and 16 (17%) as Grade 3. The mean values of FP, FBSL and age were 12.9 h, 96.55 mg% and 43.54 years for Grade 1, 13.48 h, 87.11 mg% and 40.85 years for Grade 2 and 13.37 h, 86.56 mg% and 36.18 years for Grade 3 respectively. SUVmax was found to vary between 1 and 22. It was observed that 47% (Grade 2 and 3) patients had significant cardiac FDG uptake in spite of blood sugar levels 71-125 mg%.
CONCLUSION: The degree of myocardial FDG uptake did not show significant correlation with FBSL, FP or age of the patient. Perhaps the reason lies elsewhere like insulin levels, medical treatments, fat metabolism, and myocardium status or some unexplored factors.

INTRODUCTION

Positron emission tomography (PET) with F-18-fluorodeoxyglucose (FDG) is a metabolic imaging method used widely for the evaluation of diverse group of malignancies. It has also been applied in the evaluation of myocardial viability.[1] In whole body FDG-PET, non-specific myocardial FDG uptake is frequently observed which could be focal and/or diffuse. This is normally considered as physiological uptake without any relationship to the malignancy under investigation.

In normal conditions, myocardial metabolism is oxidative and various substrates like free fatty acid, glucose and lactate are utilized. Oral glucose loading or insulin infusion enhances uptake of FDG in myocardium. Under fasting conditions, plasma blood sugar levels fall and plasma free fatty acid levels rise and there is decreased utilization of glucose by myocytes.[2] In order to avoid myocardial FDG uptake and to get better uptake of FDG in malignant cells, whole body FDG-PET studies for evaluation of malignancy are carried out in the fasting condition.[34] Ding, et al., found that 5-12 h fasting reduced the blood sugar level to < or = 120 mg% which resulted in diminished myocardial FDG uptake.[5] Some authors have reported varying degrees of myocardial FDG uptake in spite of low blood sugar levels.[6-8] de Groot, et al., found that myocardial FDG uptake had no correlation with fasting blood sugar level (FBSL), fasting period (FP) or age of the patient.[6] In a similar study, the authors reported a negative correlation between FBSL and FDG uptake, but FP and age of the patient showed no relationship.[7]

A large number of patients undergo whole body FDG-PET at our center for evaluating malignancy and we have observed varying degrees of FDG uptake in the heart of these patients. Since the studies correlating the FDG uptake with FBSL, FP and age of the patient have reported various views, we wanted to study these factors in our population. The objective of this was to correlate myocardial FDG uptake with factors like FBSL, FP and age of the patient.

MATERIALS AND METHODS

Patients

Ninety-one non-diabetic patients (62 men and 29 women, age range 7-78 years) with malignant disease were included in the study. The patients were referred to our department for whole body FDG-PET to assess or detect the disease. Estimation of FBSL was performed prior to the injection of FDG. Age and FP were recorded after enquiring with the patient.

PET imaging

Imaging studies were carried out on a dedicated full ring PET scanner (PET Advance Nxi, GE Health Care, Millwakee, USA). F-18-FDG was procured from the Medical Cyclotron Facility available at our Centre. Patients were asked to fast for more than 6 h before the test. Prior to injection, patients were well-hydrated. Patients received approximately 296-370 MBq (8-10 mCi) of F-18-FDG by intravenous injection, which was followed by rest of about 60 min.

Patients were kept in supine position on the imaging table and instructed to avoid movement of any part of their body. Emission and transmission images were acquired in 2D mode from base of skull to proximal thigh region covering 14.5 cm per bed position. At each bed position, 4 min emission and 2 min transmission data were acquired. Images were reconstructed and corrected for attenuation using the ordered-subsets expectation maximization algorithm. The processed images were displayed in transaxial, coronal, and sagittal planes.

Myocardial FDG uptake analysis

Qualitative analysis of the images was carried out by experienced Nuclear Medicine Physicians. According to the visual interpretation of the FDG image, myocardial FDG uptake was classified into four grades: No myocardial uptake = Grade 0; mild uptake (equivalent to normal liver tissue) = Grade 1; moderate uptake (>liver but < brain) = Grade 2; and marked uptake (equivalent to brain) = Grade 3. Quantitative analysis was also performed in tomographic slices by calculating SUVmax. circular/oval Region of interest (ROI) covering heart was generated and SUVmax (SUVbw [g/ml]) was noted by reading SUVmax in various slices of the coronal plane using Xeleris workstation. Determination of SUVmax was not carried out in cases having Grade-0 on qualitative analysis. Liver SUVmax was also obtained as a reference to compare with heart values. Statistical significance was established using SPSS software.

RESULTS

A comparative result of the qualitative analysis is given in Table 1. The FBSL were found between 72-127 mg%. FP varied from 5-18 h. Myocardial FDG uptake was evident in 54 (63%) of the cases. Grade 1 uptake was noted in 11 (12%) patients. Twenty-seven (30%) and 16 (%) cases showed Grade 2 and 3 uptakes respectively. There was no significant relationship between the degree of myocardial FDG uptake and blood sugar, FP and age of the patients. Various levels of myocardium uptake are illustrated in Figures 1–4. The mean value of blood sugar levels in the myocardium of 11, 27 and 16 patients with Grade 1, 2 and 3 myocardial uptake were 96.55, 87.11 and 86.55 mg%, respectively, which were not significantly different from that (94.19%) of no uptake (Grade 0) in heart of 37 patients. Similarly, age (44.3, 43.5, 40.85 and 36.18 years) and FP (14, 12.9, 13.48 and 13.37 hours) were not significantly different in patients with various degrees of myocardial FDG uptake (Grade 0, 1, 2 and 3 respectively).

Table 1

Results of qualitative analysis of myocardial F-18-fluorodeoxyglucose uptake

Figure 1

No myocardial-fluorodeoxyglucose uptake grade 0 in coronal (a) and Transaxial; (b) views

Figure 4

Myocardial-fluorodeoxyglucose uptake grade 3 in coronal (a) and Transaxial; (b) views

Myocardial-fluorodeoxyglucose uptake grade 1 in coronal (a) and Transaxial; (b) views

Myocardial-fluorodeoxyglucose uptake grade 2 in coronal (a) and Transaxial; (b) views

Myocardial SUVmax was found to vary in different grades. The comparison between myocardial SUVmax and FBSL, FP and age are shown in Figures 5–7 respectively. Widely scattered points in corresponding graphs suggest poor correlation between these parameters. Statistically, there was no significant correlation between myocardial SUVmax and FBSL, FP and Age of the patients.

Figure 5

Relationship between fasting blood sugar levels and myocardial SUVmax

Figure 7

Relationship between age and heart SUVmax

Relationship between fasting period and heart SUVmax

The mean value of SUVmax in the liver of 54 cases was found to be 3.19 ± 1.20 varying from 0.91-5.84. In these cases, myocardial SUVmax was 6.97 ± 4.92 ranging from 1-22. The ratio of heart to liver SUVmax correlated well with the visual scores.

DISCUSSION

In this study of 91 patients, the degree of myocardial FDG uptake did not show significant correlation with blood glucose level, FP or age of the patient. We found that 47% (Grade 2 and 3) of the patients had significant cardiac FDG uptake. Twenty-seven (30%) patients had Grade 2 and 16 (17%) had Grade-3 uptake in spite of blood sugar levels 87.11 ± 9.03 mg% and 86.56 ± 12.73 mg% and FP 13.48 ± 3.27 h and 13.37 ± 2.25 h respectively [Table 1]. There was no significant difference in FBSL, FP and age of the patients showing Grade 0, 1, 2 and 3 uptake [Table 1]. Study of Heart SUVmax of 54 patients having Grade 1, 2 and 3 uptakes showed no significant correlation between FBSL, FP and age of the patients [Figures 5 and 7]. Calculation of Heart SUVmax was not possible in 37 patients because the myocardium did not show uptake of FDG [Figure 1].

Our study was in agreement with previous studies reported by de Groot, et al., who studied 175 patients and found that non-specific uptake in myocardium had no significant correlation with blood glucose level, age, or FP.[6] Patricio, et al., noted that 58% of 30 cases had significant heart uptake showing no significant relationship with blood glucose levels.[8] Steinmetz, et al., reported no relationship between blood glucose or insulin levels and cardiac uptake of FDG.[9] In a study of 159 non-diabetic cases (105 men and 54 women), Kaneta, et al., observed a negative relationship between blood glucose level and heart FDG uptake[7] that was not similar to our results.

Normally myocardium utilizes free fatty acid, glucose and lactate, but under fasting conditions, plasma insulin levels fall resulting in reduced transport of glucose into myocardium. Maintaining a fasting state may help to reduce the myocardial glucose uptake. F-18-FDG is taken up and phosphorylated in myocardium, like glucose, but it is not metabolized. In order to achieve decreased myocardial FDG, it is important to keep the patient under fasting state. Blood sugar levels < 120 mg% and FP of 5-12 h was found to decrease myocardial uptake.[5] Our results indicated no significant correlation between degree of myocardial FDG uptake and FBSL, FP and age of the patient. Low blood glucose level or higher FP was not able to predict the degree of myocardial FDG uptake [Table 1].

Heart metabolism is a complex phenomenon and FP, FBSL and age may probably not be the only factors playing the role. May be other factors in the patient like fat metabolism, insulin, and glucagon levels and catecholamine need to be studied for assessing the relationship of glucose and myocardium.[2310] Moreover, many other factors like serum levels of thyroxin,[11] dehydroascorbic acid,[12] epinephrine,[13] and treatment with benzafibrate or withdrawals of benzodiazepines[14] also affect myocardial glucose uptake. Acipimox, a nicotinic acid is known to block lipolysis resulting in reduced free fatty acid and may increase myocardial uptake under fasting condition.[15] All patients included in this study were known cases of malignancy. The degree of disease aggressiveness may also be related to myocardial FDG uptake.[7] It is also important to know the myocardium status itself. Myocardial FDG uptake may vary in ischemic regions.[2] Our patients had no history of coronary artery disease. A precise assessment of the possibilities of myocardial disease was not carried out in these patients.

CONCLUSION

Based on our findings, no correlation could be established between myocardial FDG uptake and serum blood sugar, FP and age of the patient. The FDG uptake appears to be patient-specific as substrates for myocardial metabolism vary depending on the physiological, the pathological, and the pharmacological factors. Characterization of FDG uptake may be possible with exploration including large number of patients and more factors like Plasma Fatty Acid levels (affecting the substrate for myocardial metabolism), medications such as Acipimox (blocks lipid metabolism enhancing glucose uptake in heart), myocardial status like Coronary artery disease, Ischemic heart disease (CAD, IHD etc.), avidity of malignancy for FDG etc., simultaneously.