Circulation Journal  Vol.77,  January  2013

Circulation JournalOfficial Journal of the Japanese Circulation Societyhttp://www.j-circ.or.jp

he energy metabolism of the heart and the utilization of substrates including glucose, fatty acids, amino acids, lactic acid and ketone bodies depend on circumstanc-

es,1 and are primarily based on fatty acid metabolism and glu-cose metabolism in a competitive manner.2 However, a shift to anaerobic metabolism because of low oxygen supplies causes ischemic myocardium to primarily utilize glucose.3,4 Many re-ports have discussed whether maintaining glucose metabolism is important in estimating the viability of ischemic myocar-dium, and some reports indicate that improvements in left ventricular function and the prevention of cardiac events are

achieved with the use of aggressive revascularization proce-dures.5–9 The use of glucose-loaded 18F-fluoro-2-deoxyglucose (18F-FDG) PET has played a central role in helping cardiovas-cular interventionalists decide whether revascularization pro-cedures are indicated in patients with old myocardial infarc-tion (MI) with residual stenosis and angina pectoris.10–13 18F-FDG-PET has been also utilized to evaluate systemic in-flammatory diseases, including malignancies, because 18F-FDG accumulates in sites of inflammation.14,15 Therefore, appropri-ate timing for the evaluation of glucose-loaded 18F-FDG-PET images of acute MI (AMI) has been conventionally considered

T

Received January 11, 2012; revised manuscript received July 28, 2012; accepted August 28, 2012; released online October 3, 2012 Time for primary review: 27 days

Department of Cardiology (R.F., Y.H., M.N., M.I., H.T., N.T., T.T.), Kanazawa PET Center (H.B.), Kanazawa Cardiovascular Hospital, Kanazawa, Japan

Mailing address: Ryota Fukuoka, MD, Department of Cardiology, Kanazawa Cardiovascular Hospital, Ha16-Tanakamachi, Kanazawa 920-0007, Japan. E-mail: mm970076ryota2000@yahoo.co.jp

ISSN-1346-9843 doi: 10.1253/circj.CJ-12-0011All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp

Serial Changes in Glucose-Loaded 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography,

99 mTc-Tetrofosmin and 123I-Beta-Methyl-p-Iodophenyl-Penta-Decanoic Acid Myocardial Single-Photon Emission

Computed Tomography Images in Patients With Anterior Acute Myocardial Infarction

Ryota Fukuoka, MD; Yuki Horita, MD; Masanobu Namura, MD; Masatoshi Ikeda, MD; Hidenobu Terai, MD; Naoto Tama, MD; Toshimitsu Takagi, MD; Hisashi Bunko, MD

Background:  18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is assumed to be the most useful  method  for  evaluating  the  viability  of  the myocardium.  However,  there  are  few  reports  regarding  serial changes in 18F-FDG-PET images of acute myocardial  infarction (AMI). We evaluated serial changes in glucose-loaded 18F-FDG-PET, 123I-β-methyl-p-iodophenyl-penta-decanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and 99 mTc-Tetrofosmin (TF) gated SPECT images in patients with AMI.

Methods and Results:  We  enrolled  7  consecutive  patients with  first  anterior  AMI who  successfully  underwent percutaneous coronary  intervention  (PCI).  18F-FDG-PET  images were obtained  in  the acute, subacute, chronic, mid-term and long-term phases. 123I-BMIPP and 99 mTc-TF SPECT images were obtained in the subacute, chronic, mid-term and long-term phases. We determined the total defect score (TDS) for each image. The TDS of the glu-cose-loaded 18F-FDG-PET, 123I-BMIPP and 99 mTc-TF SPECT images indicated significant serial decrease (P<0.001). Comparing these  images,  the TDS of  the glucose-loaded 18F-FDG-PET images was  larger  than that of  the 123I-BMIPP and 99 mTc-TF SPECT images, and the TDS indicated 18F-FDG-PET>123I-BMIPP>99 mTc-TF in all phases.

Conclusions:  The defect areas of glucose-loaded 18F-FDG-PET images were significantly larger than those of 123I-BMIPP and 99 mTc-TF SPECT images during 9 months follow-up of patients with successful PCI for anterior AMI. Additionally, the impairment of glucose metabolism was prolonged.    (Circ J  2013; 77: 137 – 145)

Key Words:  Acute myocardial infarction; Glucose-loaded 18F-FDG-PET; Myocardial viability; Percutaneous coronary intervention

ORIGINAL  ARTICLEImaging

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138 FUKUOKA R et al.

to be 3 or 4 weeks after the onset of the infarction when in-flammation at the infarction site is stabilized. Additionally, some reports of fasting 18F-FDG-PET affirm the influence of inflammation on infarcted myocardium.16

Editorial p 51

However, there are no reports of the changes in myocardial damage with serial 18F-FDG-PET following percutaneous cor-onary intervention (PCI) for AMI, and both the use of glucose-loaded 18F-FDG-PET alone to assess myocardial viability after reperfusion of MI and the appropriate timing for evaluation are still matters of argument. In addition, 1 report indicates that myocardial viability could be evaluated more precisely by comparing the results of glucose-loaded 18F-FDG-PET with those of fatty acid metabolism and myocardial perfusion.17

In this study, we evaluated the serial changes in glucose loaded 18F-FDG-PET, 123I-β-methyl-p-iodophenyl-penta-dec-anoic acid (BMIPP) single-photon emission computed tomog-raphy (SPECT) and 99 mTc-Tetrofosmin (TF) gated SPECT images in patients with AMI in order to estimate the capabil-ity of glucose-loaded 18F-FDG-PET in evaluating myocardial viability.

MethodsSelection of PatientsWe studied 7 consecutive patients who were admitted to hos-pital with a diagnosis of first anterior AMI. Each patient suc-cessfully underwent PCI and obtained good coronary flow without slow or no reflow. All of the patients had culprit le-sions in the proximal left anterior descending artery, and only patients with single-vessel disease were enrolled in this study. Patients with severe cardiac failure in whom it was difficult to obtain glucose-loaded 18F-FDG-PET images in the acute phase

were excluded.The study protocol was approved by the institutional ethics

committee, and all patients gave informed consent.

Examination Schedule of Myocardial Imaging and Serological DataEach patient was treated with reperfusion therapy within 24 h of the onset of the MI. Glucose-loaded 18F-FDG-PET images were obtained in the acute phase (days 2–5), subacute phase (2 weeks), chronic phase (1 month), mid-term followed phase (3 months) and long-term followed phase (9 months). 123I-BMIPP, resting 99 mTc-TF SPECT and quantitative gated SPECT images were obtained in the subacute, chronic, mid-term and long-term followed phases. Serological examination was per-formed at 6-h intervals in the acute phase to estimate the peak levels of cardiac enzymes. High-sensitivity C-reactive protein (hs-CRP) levels were measured in the acute, subacute and chronic phases as a marker of inflammation, considering the influence of local inflammation on the images.

Glucose-Loaded 18F-FDG-PET Imaging Whole body PET imaging equipment (ECAT ACCEL Siemens) was used, and the images were acquired with 10 min of emission after 5 min of transmission scans. After undergoing an overnight fast, the patient was given 75 g of oral glucose. The images were ob-tained with an insulin-bolus administration method in which the patient was injected intravenously with insulin, in a dose that depended on 1-h blood glucose levels, followed by intra-venous administration of 259 Mbq of 18F-FDG.18 The dose of insulin was determined as follows: insulin dose = (blood glu-cose level – 130) / 10 unit, given a blood glucose level >130 mg/dl. The acquisition of the early-phase images began 1 h after the intravenous administration of 18F-FDG, and the acquisition of the late-phase images began 3 h after 18F-FDG administration.

TF  Gated  SPECT  Imaging We used 2-detector SPECT equipment with a low-energy, high-resolution collimator

Figure 1.    Comparative performance of 18F-FDG-PET, 123I-BMIPP and 99 mTc-TF SPECT images in a myocardial infarction model. We obtained images using the 3.0 cm defect-phantom model (Kyoto Kagaku) and compared the 18F-FDG-PET, 99 mTc-TF SPECT, and 123I-BMIPP SPECT images. BMIPP, 123I-β-methyl-p-iodophenyl-penta-decanoic acid single-photon emission computed tomog-raphy (SPECT); 18F-FDG-PET, 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography; 99 mTc-TF, 99 mTc-Tetrofosmin (TF) gated SPECT.

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139Serial Changes in 18F-FDG-PET for AMI

(Millennium VG, GE). The images were acquired from 360 degrees in 60 directions with 6 degree intervals at 40 s for each direction with the detectors facing each other. After undergo-ing an overnight fast, the patient was administered 740 MBq of 99 mTc-TF intravenously, and the SPECT imaging began 40 min later. The energy peak during the acquisition of the SPECT images was 140 keV for 99 mTc, and the window width was ±10%.

123I-BMIPP SPECT Imaging To complete the 123I-BMIPP SPECT imaging, we used the same equipment used for the 99 mTc-TF SPECT imaging. After undergoing an overnight fast, the patient was administered 148 MBq of 123I-BMIPP intravenously, and the SPECT imaging began 15 min later in the same manner as for the 99 mTc-TF SPECT imaging. The energy peak during the acquisition of the SPECT images was 159 keV for 123I, and the window width was ±10%.

Analysis of the ImagesReconstructed images of the left ventricle of each patient (short-axis slices, vertical long-axis slices and horizontal long-axis slices) were created for non-gated data. To complete the image analyses, a myocardial polar map of each patient’s left ven-tricle was divided into 17 segments.19,20 For each segment, 3 specialists, comprising 2 cardiovascular specialists and 1 nu-clear medicine specialist, visually scored the degree of reduced accumulation in the glucose-loaded 18F-FDG-PET, 99 mTc-TF and 123I-BMIPP images using a 5-point grading system: 0=nor-mal, 1=mild reduction, 2=moderate reduction, 3=severe re-duction, 4=no reduction. The defect score (DS) was defined as the mean of the scores reported by the 3 analysts. In addition, the total DS (TDS) was defined as the sum of the DS of each myocardial scan image, and the TDS was calculated for each patient. To analyze the glucose-loaded 18F-FDG-PET images, late-phase images were used. To analyze the 99 mTc-TF and 123I-BMIPP SPECT images, the rest images were used. We analyzed the late-phase glucose-loaded 18F-FDG-PET images because the defect areas of the glucose-loaded 18F-FDG-PET images were similar in the early and late phases. We used a long imaging time to compensate for the decreasing counts of 18F-FDG in the late-phase, and the late-phase images presented clear definitive boundaries because of the lower background activity.

Ejection fraction (EF) values were analyzed using 99 mTc-TF gated SPECT images to evaluate the global cardiac function.

Evaluation of Phantom Model Images With the Imaging EquipmentWe obtained images using the 3.0-cm defect-phantom model (Kyoto Kagaku) and compared the 18F-FDG-PET, 99 mTc-TF SPECT and 123I-BMIPP SPECT images obtained with the equipment (Figure 1). The 99 mTc-TF SPECT images showed large defect areas of reduced myocardial uptake around the infarct regions (defect-phantom) because of the spatial resolu-tion and the influence of low-energy photons.11 However, virtually equal defect-images were obtained using 18F-FDG-PET and 123I-BMIPP images.

Statistical AnalysesThe data are expressed as the mean ± SD. A repeated measures ANOVA test was used to analyze continuous data. The TDS values among the 3 groups were determined using the Bonfer-roni/Dunn test for post-hoc analysis. The statistically signifi-cant level was defined as P<0.05. The analyses were performed using statistical analysis software (StatView; SAS Institute Inc, Cary, NC, USA).

ResultsPatients’ Characteristics (Table 1)The mean age of the patients (6 males, 1 female) was 61.1± 12.7 years. The average duration from the onset of MI to hos-pitalization was 5.0±3.5 h. The mean HbA1c level was 6.6±1.3% (JDS: Japan diabetes Society), and 4 patients had diabetes mellitus. The mean hs-CRP level obtained immediately after hospitalization was 0.92±1.41 mg/dl, and the peak serum lev-els of creatine kinase (CK) and CK-MB were 3,175±1,531 U/L and 301±144 mg/dl, respectively. The mean LVEF assessed with left ventriculography immediately after PCI was 50.4±7.2%, and the mean cardiac index measured by Swan-Ganz catheter was 3.19±0.48 L/min/m2.

Number of Examined Days of Myocardial Scan Imaging After Onset of MIThe mean number of examined days of glucose-loaded 18F-FDG-PET, 123I-BMIPP and 99 mTc-TF SPECT images was 4±1 days for the acute phase, 20±4 days for the subacute phase, 37±3 days for the chronic phase, 122±12 days for the mid-term followed phase and 275±49 days for the long-term fol-lowed phase, as shown in Table 2.

Serial Changes in hs-CRP (Figure 2)The mean hs-CRP values of the examined glucose-loaded 18F-FDG-PET images were 4.88±5.37 mg/dl in the acute phase, 0.15±0.20 mg/dl in the subacute phase and 0.12±0.07 mg/dl in the chronic phase. hs-CRP showed normalization within 3 weeks from the onset of AMI.

Serial Changes in TDS of Myocardial Scan ImagingThe mean TDS of the glucose-loaded 18F-FDG-PET images was 22.3±10.5 in the acute phase, 20.7±7.9 in the subacute phase, 14.9±6.8 in the chronic phase, 15.6±7.5 in the mid-term

Table 1. Characteristics of the 7 Patients With Acute Myocardial Infarction

Age (years) 61.1±12.7

Sex (M/F) 6/1

Culprit lesion, seg.6/seg.7 6/1

Time from onset (h) 5.0±3.5

Diabetes mellitus (+/–) 4/3

    Glucose (on adm.) (mg/dl) 195±54　　    HbA1c (JDS) (%)   6.6±1.13

Lipids

    TC (mg/dl) 221±54　　    HDL-C (mg/dl) 48.3±8.1　　    TG (mg/dl) 130±106

High-sensitivity CRP (on adm.) (mg/dl) 0.92±1.41

Cardiac enzymes

    Max. CK (U/L) 3,175±1,531

    Max. CK-MB (mg/dl) 301±144

    Max. AST (mg/dl) 289±92　　    Time to CK-max. (h) 9.9±4.8

LVEF on angioplasty (%) 50.4±7.2　　CI by SG (L/min/m2) 3.19±0.48

Adm., admission; AST, aspartate transaminase; CI, cardiac index; CK, creatine kinase; CK-MB, CK myocardial bound; CRP, C-reac-tive protein; HDL-C, high-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; seg., segment; SG, Swan-Ganz cath-eter; TC, total cholesterol; TG, triglycerides.

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140 FUKUOKA R et al.

followed phase and 12.8±7.6 in the long-term followed phase. The serial TDS of the glucose-loaded 18F-FDG-PET images presented a statistically significant time-dependent decrease toward the long-term followed phase (P<0.001) (Figure 3A).

The mean TDS of the 123I-BMIPP SPECT images was 15.0±9.6 in the subacute phase, 10.0±6.6 in the chronic phase, 10.0±6.2 in the mid-term followed phase and 9.0±5.8 in the long-term followed phase. The serial TDS of the 123I-BMIPP images presented a statistically significant time-dependent decrease approaching the long-term followed phase (P<0.05), similar to the changes observed in the glucose-loaded 18F-FDG-PET images (Figure 3B).

The mean TDS of the 99 mTc-TF SPECT images was 12.6±9.1 in the subacute phase, 10.0±8.0 in the chronic phase, 7.7±5.3 in the mid-term followed phase and 7.7±6.2 in the long-term followed phase. The serial TDS of the 99 mTc-TF images presented a statistically significant time-dependent decrease approaching the long-term followed phase (P<0.01), the same as that seen in the glucose-loaded 18F-FDG-PET and 123I-BMIPP SPECT images. In addition, the TDS values were similar for the mid-term and long-term followed phases (Figure 3C).

Comparison of Serial Changes in TDS in the Glucose-Loaded 18F-FDG-PET, 123I-BMIPP SPECT and 99 mTc-TF SPECT ImagesTable 3 presents the serial changes in TDS for the 3 radio-pharmaceuticals. The TDS values of the glucose-loaded 18F-FDG-PET images were significantly larger than those of the 123I-BMIPP SPECT and 99 mTc-TF SPECT images in all phas-es. The TDS values of the 123I-BMIPP SPECT images tended to be larger than those of the 99 mTc-TF SPECT images, except in the chronic phase, which did not show any significant dif-ferences.

Serial Changes in EF Values Analyzed Using 99 mTc-TF SPECT ImagesThe mean EF estimated from the 99 mTc-TF gated SPECT im-ages was 57.1±6.9% in the subacute phase, 62.7±4.7% in the chronic phase, 64.9±8.5% in the mid-term followed phase and 60.7±6.3% in the long-term followed phase (Figure 4). Serial changes in EF values presented statistically significant im-provements (P<0.05).

Case PresentationA 79-year-old woman was admitted to hospital because of

Table 2. Number of Examined Days of Myocardial Scan Imaging After Onset of Infarction

Acute phase (2–5 days)

Subacute phase (2 weeks)

Chronic phase (4 weeks)

Followed phase

Mid-term (3–4 months)

Long-term (9 months)

18F-FDG-PET (days) 4±1 20±4 37±3 122±12 278±50123I-BMIPP (days) 19±4 38±2 122±11 278±5099mTc-TF (days) 20±2 37±4 121±13 270±55

Mean ± SD (days) 4±1 20±4 37±3 122±12 275±49

BMIPP,  123I-β-methyl-p-iodophenyl-penta-decanoic  acid  single-photon  emission  computed  tomography  (SPECT); 18F-FDG-PET,  18F-fluoro-2-deoxyglucose  (FDG)  positron  emission  tomography;  99mTc-TF,  99mTc-Tetrofosmin  (TF) gated SPECT.

Figure 2.    Serial changes in high-sensitivity C-reactive protein. NS, not significant.

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141Serial Changes in 18F-FDG-PET for AMI

Figure 3.    Serial changes in the total defect scores (TDS) of (A) glucose-loaded  18F-FDG-PET  images,  (B) 123I-BMIPP SPECT images and (C) 99 mTc-TF  SPECT  images.  BMIPP, 123I-β-methyl-p-iodophenyl-penta-decanoic acid single-photon emis-sion computed tomography (SPECT); 18F-FDG-PET, 18F-fluoro-2-deoxyglu-cose  (FDG)  positron  emission  to-mography;  99 mTc-TF,  99 mTc-Tetro-fosmin (TF) gated SPECT.

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142 FUKUOKA R et al.

AMI with the culprit lesions in the proximal left anterior de-scending coronary artery. Additionally, the patient had diabe-tes mellitus as an underlying disease. The occluded coronary artery was successfully reperfused during urgent coronary angioplasty, and the peak serum levels of CK and CK-MB were 4,425 U/L and 477 mg/dl, respectively. As shown in Figure 5, the defect areas in the glucose-loaded 18F-FDG-PET images were larger than those in the 99 mTc-TF SPECT and 123I-BMIPP SPECT images in all phases. Additionally, com-paring the 123I-BMIPP SPECT and 99 mTc-TF SPECT images, the 123I-BMIPP SPECT images showed larger defect areas until the mid-term followed phase (4 months later), and both images presented similar defect areas in the long-term fol-lowed phase.

DiscussionThe myocardium responds to ischemia by switching the en-ergy substrate from fatty acid metabolism to glucose metabo-lism.2 It is widely known and many reports show that glucose metabolism persists in the impaired myocardium in patients with an old MI and that left ventricular function is improved by PCI. However, it is unclear whether a higher detecting ca-

pability for myocardial viability should be adopted in patients who successfully undergo PCI to treat AMI.21,22 Some reports indicate that myocardial viability is overestimated when eval-uating fasted 18F-FDG-PET images because 18F-FDG accumu-lates in inflammation sites.11,23 We considered that the defect areas of 18F-FDG-PET images taken in the acute phase would be smaller than those taken in the subacute phase because 18F-FDG accumulates in the leukocytes that infiltrate the infarct-related segments. However, in this study the defect areas ob-served in the acute phase were larger than those observed in the subacute phase. Obvious increases in inflammatory respons-es in infarcted myocardium were observed in the acute phase, together with significant increases in hs-CRP values. These results suggest that the influence of local inflammation associ-ated with AMI on glucose-loaded 18F-FDG-PET images is much smaller than that of severely impaired glucose metabo-lism in the damaged myocardium.

In our study, the defect areas in the glucose-loaded 18F-FDG-PET images were larger than those in the images from the other myocardial scans in all examined phases. We esti-mated the influence of the imaging equipment and image processing in order to confirm our results. We evaluated each defect image using a 3.0-cm defect-phantom model to inves-

Table 3. Comparison of Serial Changes in the Total Defect Score for the Glucose-Loaded 18F-FDG-PET, 123I-BMIPP SPECT and 99mTc-TF SPECT Images

Acute phase

Subacute phase

Chronic phase

Followed phase

Mid-term Long-term18F-FDG-PET 22.3±10.5 20.7±7.9 14.5±6.8 15.5±7.5 12.8±7.6123I-BMIPP 15.0±9.6 10.0±6.6 10.0±6.2   9.0±5.699mTc-TF 12.6±9.1 10.0±8.0   7.7±5.3   7.7±6.2

*P<0.05, **P<0.01.Abbreviations as in Table 2.

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Figure 4.    Serial changes in the ejection fraction (EF) values analyzed using 99 mTc-TF SPECT images. 99 mTc-TF, 99 mTc-Tetrofosmin (TF) gated single-photon emission computed tomography.

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143Serial Changes in 18F-FDG-PET for AMI

tigate procedural influences. As a result, virtually equal sizes of the defect areas with clear edges were detected in the im-ages of both 18F-FDG-PET and 123I-BMIPP; however, the edges of the defect areas in the 99 mTc-TF images were blurred, and the defect areas were overestimated. Considering the results of the phantom model imaging, we concluded that the obser-vation of larger defect areas in the glucose-loaded 18F-FDG-PET images of impaired myocardium compared with those seen in the 123I-BMIPP and 99 mTc-TF SPECT images was not influenced by either the imaging equipment or image process-ing. The serial changes in the 18F-FDG-PET, 123I-BMIPP and 99 mTc-TF SPECT images in our study indicated that the 18F-FDG-PET images of possibly underestimated the myocardial viability of the infarcted myocardium, even in the long-term followed phase.

With regard to the underestimation of myocardial viability by the glucose-loaded 18F-FDG-PET images taken after reper-fusion for AMI, reverse mismatch, which presents as a low uptake in 18F-FDG-PET images and a high uptake in 99 mTc-TF and 123I-BMIPP SPECT images, was reported in patients with multivessel coronary disease, left bundle branch block, and diabetes mellitus, and in patients who underwent thrombolysis or PCI.23–26 Shirasaki et al discussed the reasons for the under-estimation of myocardial viability and hypothesized that well-oxygenated myocardium obtained by reperfusion causes an increase in the aerobic metabolism of fatty acids and a de-crease in anaerobic metabolism, such as glucose metabolism, and these situations are unchanged after glucose loading.27 Myears et al reported that the major metabolic substrate pres-ent in the infarct region after recovery from ischemia was fatty acids and that glucose metabolism accounted for only 25% in

their study of dogs.28 Schwaiger and Pirich29 described reverse mismatch as a consequence of incomplete metabolic standard-ization. For example, low glucose use in patients with insulin resistance, which is frequently observed in coronary artery disease, leads to decreased FDG uptake, even in areas that are normally perfused. They also indicated that biological factors cause altered substrate use in normally perfused myocardium. The reverse mismatch of low uptake of glucose-loaded 18F-FDG-PET images might be explained by these reports.

On the other hand, Kanayama et al30 reported 1 case of imaging of unstable angina in which defect areas of glucose-loaded 18F-FDG-PET images taken before percutaneous trans-luminal coronary angioplasty improved 3 months after PCI. Their report highlights the fact that glucose metabolism is sup-pressed in myocardial stunning regions associated with isch-emia and is improved with recovery of myocardial perfusion. This observation conflicts with the hypothesis proposed by Shirasaki et al. Mesotten et al discuss reverse mismatch when comparing glucose-loaded 18F-FDG-PET and 13NH3-PET im-ages in patients with AMI and they conclude that the myocar-dium might utilize substrates other than glucose and fatty acids, such as lactic acid, in ischemic conditions because of its om-nivorous nature.31 Beyersdolf et al reported in an animal study that in cases of single-vessel disease, increased glucose me-tabolism associated with increases in blood flow and endoge-nous adenosine in normal areas adjacent to the infarct region causes mild increases in 18F-FDG uptake and excessive con-traction of the myocardium in areas not affected by culprit lesions because of abnormalities in vasodilators after MI.32 Godino et al33 reported that in the first AMI of single-vessel disease, abnormal accumulation of 18F-FDG outside of isch-

Figure 5.    Serial changes in 18F-FDG-PET, 123I-BMIPP and 99 mTc-TF SPECT images in a 79-year-old woman with diabetes mellitus who presented with an anterior acute myocardial infarction. BMIPP, 123I-β-methyl-p-iodophenyl-penta-decanoic acid single-photon emission computed tomography (SPECT); 18F-FDG-PET, 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography; 99 mTc-TF, 99 mTc-Tetrofosmin (TF) gated SPECT.

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144 FUKUOKA R et al.

emic areas was observed, which was caused by the stimulation of GLUT-1 because of the inflammation associated with the MI. They also observed abnormal accumulation of 18F-FDG at 1 year after the AMI.

As has been discussed, myocardial metabolism in AMI fluc-tuates, and changes in the glucose metabolism of normal sur-rounding areas, as well as that of the ischemic regions, can be seen. Therefore, evaluating myocardial viability after reperfu-sion of MI using 18F-FDG-PET imaging alone is not effica-cious. However, 18F-FDG-PET imaging has advantages. Gen-erally, it is well known that 123I-BMIPP imaging will “memorize” acute ischemic events for 2 weeks.34 Additionally, the defect areas in the glucose-loaded 18F-FDG-PET images were sig-nificantly larger than those in the 123I-BMIPP images in our study. Impaired glucose metabolism was prolonged for longer than fatty acid metabolism, and 18F-FDG-PET images memo-rize acute ischemic events longer do than 123I-BMIPP images.

We performed several rounds of radionuclide examination in this study. The sum of the effective radiation doses in 1 examined phase of 18F-FDG-PET, 99 mTc-Tetrofosmin and 123I-BMIPP myocardial SPECT imaging was 14.95 mSv in our study. The total radiation dose used for each patient in all stud-ied phases was 67.72 mSv, and the effective dose of 1 cardiac catheterization was reported to be 22.7 mSv by the Interna-tional Commission on Radiological Protection (ICRP)35 and in a previous report.36 Therefore, the total effective dose used in the radionuclide study of each patient during the 9 months of this study was similar to that used in 3 instances of cardiac catheterization.

Study LimitationsWe used glucose-loaded 18F-FDG-PET imaging with bolus ad-ministration of insulin in this study. However, the possibility that elevated blood levels of free fatty acids resulting from insulin resistance and depleted conditions blocked the accu-mulation of 18F-FDG cannot be refuted because diabetic pa-tients were included in this study. Therefore, we should have measured the blood levels of free fatty acids and insulin dur-ing 18F-FDG-PET imaging. Concerning the method of glucose loading, the insulin clamp technique is reported to be preferred for patients with diabetes mellitus.19,37 However, the same reports also show that the influence can be minimized by using late-phase images taken 3 h after the administration of 18F-FDG. We also used late-phase images in this study. Because we utilized SPECT and PET images to compare myocardial perfusion with glucose metabolism, the possibility that differ-ences in modality caused the falsely positive perfusion-me-tabolism mismatch cannot be refuted. However, 1 report indi-cates that this influence is larger in the anterior walls of females and in the inferior walls of all patients.23 We considered the influence to be limited in this study because we included only 1 female patient and all of the evaluated vessels were in the anterior walls of the patients. One report identifies interleukin (IL)-6 and IL-2 as markers of inflammation, which are influ-enced by accumulation of 18F-FDG [31], and suggests that the use of hs-CRP alone as a marker of inflammation in this study was insufficient.

ConclusionsThe defect areas of glucose-loaded 18F-FDG-PET images were significantly larger than those of 123I-BMIPP and 99 mTc-TF SPECT images taken during an observation period of 9 months in patients who successfully underwent PCI to treat anterior AMI. Additionally, the impairment of glucose metabolism was

prolonged.

DisclosuresThe authors declare that they have no conflicts of interest.

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