Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by<Superscript>123</Superscript>I-BMIPP SPECT and<Superscript>99m</Superscript>Tc-tetrofosmin electrocardiographically gated SPECT

OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p > 0.05) but had a significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p < 0.005) and perfusion (p < 0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.     

Prediction of cardiac events in patients with dilated cardiomyopathy using <Superscript>123</Superscript>I-BMIPP and <Superscript>201</Superscript>Tl myocardial scintigraphy

Objective Various clinical trials for dilated cardiomyopathy (DCM) have demonstrated that the prognosis as well as cardiac function is improved by the administration of beta-blocker therapy. On the other hand, ¹²³I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) reflects myocardial fatty acid metabolism and is considered to be a more sensitive tracer than perfusion tracers. In this study, the efficacy of DCM for the evaluation of myocardial damage and the prediction of cardiac events was studied using ¹²³I-BMIPP and ²⁰¹TI (Tl) myocardial scintigraphy. Methods Study subjects comprised 33 DCM patients, divided into a cardiac event group (event, n = 9) and an event-free group (event free, n = 24). An extent score (ES) and severity score (SS) were calculated for each BMIPP image. BMIPP and Tl images were divided into 17 segments, and total defect scores (TDS) were calculated for each. The TDS of the BMIPP and Tl images were compared with score differences greater than or equal to 4 and less than 4 defined as mismatch and non-mismatch, respectively. Results The TDS of BMIPP was significantly higher in the event group than in the event-free group (P < 0.05). The ES and SS were significantly higher in the event group than in the event-free group (P < 0.01). The comparison in the 2 × 2 contingency tables showed that the occurrence of non-mismatch was significantly higher in the event-free group (χ² test; P < 0.01). The ES of BMIPP was a significant predictor of cardiac events in the multivariate analysis (P < 0.01). Conclusions These results suggest that the ES for BMIPP is useful as a predictor of cardiac events in DCM.     

Abnormal retention of<Superscript>99m</Superscript>Tc-TF in a hamster model of cardiomyopathy analyzed by<Superscript>99m</Superscript>Tc-TF and<Superscript>125</Superscript>I-BMIPP autoradiography

OBJECTIVE: Enhanced washout of 99mTc-tetrofosmin (TF) has been reported in patients with hypertrophic cardiomyopathy (HCM). Here, using quantitative dual-autoradiography, the relationship between TF retention abnormality and metabolism depicted by 125I-BMIPP uptake was investigated quantitatively in a hamster model of cardiomyopathy. METHODS AND RESULTS: Early and delayed TF images were obtained at 5 min (7 cardiomyopathic and 5 normal hamsters) and 60 min (8 cardiomyopathic and 5 normal hamsters) after injection, respectively. BMIPP image was obtained 5 min after injection. Five cardiomyopathic and 5 normal hamsters were evaluated histologically. Percent uptake of TF and BMIPP in the heart was measured by an auto-well counter. The left ventricular wall was divided into 12 segments, and the relative regional uptake of TF and BMIPP was measured for each segment. Heterogeneity of radioactive distribution was determined by the standard deviation (SD) of radioactive counts in the left ventricular wall on autoradiogram. The uptake of early TF, delayed TF, and BMIPP in cardiomyopathic hamsters was 8.8%, 20.3%, and 25.3% lower than that in normal hamsters, p < 0.05, p < 0.01, and p < 0.001, respectively. In normal hamsters, distribution of radioactivity in all images was homogeneous, and the SD values were about 13. In cardiomyopathic hamsters, heterogeneous distribution was observed on all images, and the degree of heterogeneity was marked on delayed TF and BMIPP images. The SD was 19.7 +/- 1.2 for early TF image, 25.5 +/- 1.4 for delayed TF image, and 31.7 +/- 2.4 for BMIPP image, respectively. A weak linear correlation was observed between the relative regional uptake of the delayed TF and BMIPP in cardiomyopathic hamsters (r = 0.57). Electron microscopy demonstrated ultra-structural changes in mitochondria of cardiomyopathic hamsters. CONCLUSION: Degree of retention abnormality on delayed TF image corresponded to the metabolic abnormality, probably due to mitochondrial dysfunction, depicted on BMIPP imaging.     

Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.

The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. RESULTS: In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. CONCLUSION: In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.     

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy

Serial change of the metaiodobenzylguanidine iodine-123 (¹²³I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and ¹²³I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30–60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of ¹²³I-MIBG did not differ significantly from that of the controls. The washout of ¹²³I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15–45 min) was significantly larger in DCM than in the controls (21.2%±7.5% vs. 5.3%±4.0%, P <0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = –0.72 P < 0.05). For ²⁰¹TI, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the ¹²³I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease. Offprint requests to: K. Yamakado     

<Superscript>11</Superscript>C-methionine (MET) and <Superscript>18</Superscript>F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma

Purpose  The purpose of this prospective study was to clarify the individual and combined role of l-methyl-¹¹C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades. Materials and methods  Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUV_max), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining. Results  On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUV_max and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUV_max and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUV_max of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01). Conclusions  PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.     

Characteristics of myocardial18F-fluorodeoxyglucose positron emission computed tomography in dilated cardiomyopathy and ischemic cardiomyopathy

Myocardial 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has been used to assess myocardial ischemia and viability, but few studies have conducted on FDG-PET for dilated cardiomyopathy (DCM). We investigated myocardial FDG uptake in patients with DCM in comparison with ischemic cardiomyopathy (ICM). Twenty-four patients with heart failure were included in this study. Fourteen of them were diagnosed as DCM and the other 10 were ICM. All of them underwent myocardial FDG-PET at fasting and after glucose loading the same day. FDG uptake was quantified by the ratio of the counts at the heart to those at the liver (H/L ratio). Left ventricular (LV) function was measured by echocardiography. We classified FDG distribution patterns in the myocardium in the fasting state into 3 types (faint uptake, regional uptake and diffuse uptake). In DCM patients, 5 had faint uptake, 7 had regional uptake, and the other 2 had diffuse uptake. On the other hand, all ICM patient had regional uptake (p < 0.05). In DCM, there were no significant relationships between the patterns and LV functions. On the other hand, there were close correlation between the H/L ratio after glucose loading and the left ventricular ejection fraction (r = 0.680, p < 0.01). The changes in PET images caused by glucose loading were classified into 2 types (non-reversing and reversing patterns). DCM significantly showed a non-reversing pattern (86%, 12 of 14 patients) whereas ICM showed mainly a reversing pattern (70%, 7 of 10 patients; p < 0.05). In conclusion, myocardial FDG uptake after glucose loading may indicate a myocardial viable mass although FDG uptake at fasting was not evidently related to LV function. The change in the pattern of the FDG image from fasting to glucose loading may be useful in differentiating DCM from ICM.     

Characterization of Japanese standards for myocardial sympathetic and metabolic imaging in comparison with perfusion imaging

Objective  The standard patterns of myocardial radiotracer distribution of ¹²³I-metaiodobenzylguanidine (MIBG) and ¹²³I-β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) should be defined in a Japanese population. The purpose of this study was to present and provide data on the characteristics of MIBG and BMIPP with respect to myocardial single photon emission computed tomography. Methods  The normal database included ¹²³I-MIBG and ¹²³I-BMIPP imaging and a ^99mTc-sestamibi/tetrofosmin myocardial perfusion study. The projection images were transferred by digital imaging and communications in medicine (DICOM) format and reconstructed and analyzed with polar maps. Results  The projection data from multiple centers were successfully transferred to a common format for SPECT reconstruction. When the average values were analyzed using a 17-segment model, MIBG uptake in the inferior and apical wall appeared to be slightly lower than anterior uptake (P < 0.05). The inferior and apical uptake of MIBG has a larger standard deviation (10.7 units in males, 12.6 units in females). BMIPP uptakes in the septal wall have higher than that of ^99mTc-tracer uptake (P < 0.05). Conclusion  Myocardial sympathetic nerve and metabolic scintigraphy data that were specific for the Japanese population were generated and found to be different from that of perfusion tracers. The normal database can serve as a standard for nuclear cardiology work conducted in Japan.     

<Superscript>123</Superscript>I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after rotational atherectomy

Background During rotational atherectomy (RA), the coronary atherosclerotic plaque is largely pulverized into microdebris, which may cause serious hemodynamic instability owing to significant segmental left ventricular asynergy embolization of the distal microvasculature by atheromatous debris and associated vasospasm. Objective To evaluate the usefulness of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) in the examination of microvascular embolization after RA. Methods and results Nineteen patients with stable effort angina pectoris who had undergone RA were evaluated in this study. Left ventricular ejection fraction (LVEF) was determined by left ventriculography immediately before and after RA. The serum concentration of creatine phosphokinase (CPK), creatine phosphokinase-myocardial band (CPK-MB) isozyme, and cardiac troponin-T was determined after RA. ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) and ¹²³I-MIBG scintigraphic examinations were also performed 1 day after RA. The regional defect score (RDS) was determined from ^99mTc-MIBI scintigraphic findings, while early and delayed RDS, heart-to-mediastinum count ratios (H/M ratios), and washout rate (WR) were determined from ¹²³I-MIBG scintigraphy. After RA, the left ventriculographic LVEF mildly decreased by ≤10% in ten patients (group A), but it decreased by >10% in the remaining nine patients (group B). There were no differences in baseline clinical characteristics between the two groups. The CPK, CPK-MB isozyme, troponin-T, RDS by ^99mTc-MIBI, H/M ratios, and WR after RA were similar in the two groups. However, the RDSs determined from early and delayed ¹²³I-MIBG in group A were significantly lower than those in group B (4.5 ± 3.8 vs. 13.4 ± 10.8, P < 0.05; 9.0 ± 6.3 vs. 17.7 ± 10.0, P < 0.05, respectively). Moreover, there were significant correlations between delta LVEF and troponin-T (r = 0.54, P < 0.05) and RDSs of early and delayed ¹²³I-MIBG (r = 0.46, P < 0.05; r = 0.64, P < 0.05, respectively). Conclusions These findings suggest that ¹²³I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after RA.     

Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: Assessment with iodine-123-labelled beta-methyl-branched fatty acid

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methylbranched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress²⁰¹Tl tomography in patients with chronic coronary artery disease.¹²³I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection²⁰¹Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible²⁰¹Tl defects, equally decreased uptake on both reinjection²⁰¹Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection²⁰¹Tl in 26 (11%). On the other hand, among 90 segments with non-reversible²⁰¹Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively,P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection²⁰¹Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection²⁰¹Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection²⁰¹Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection²⁰¹Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.     

Detection of gastric cancer using <Superscript>18</Superscript>F-FLT PET: comparison with <Superscript>18</Superscript>F-FDG PET

Purpose  We prospectively investigated the feasibility of 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. Methods  A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. Results  For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. Conclusion  FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.     

Correlation of <Superscript>18</Superscript>F-FLT and <Superscript>18</Superscript>F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

Purpose The nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG). Methods A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. Results The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). Conclusion The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.     

<Superscript>11</Superscript>C-acetate PET imaging of lung cancer: comparison with <Superscript>18</Superscript>F-FDG PET and <Superscript>99m</Superscript>Tc-MIBI SPET

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A positive correlation was not observed between either AC or MIBI uptake and the degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did correlate with the degree of cell dedifferentiation. In lung adenocarcinoma, there was a weak correlation between aggressiveness and FDG uptake, but no correlation was evident for AC and MIBI. In addition, a positive correlation was not observed between AC or MIBI uptake and postoperative recurrence in lung adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence. Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion, for the purpose of tumour identification, AC PET was inferior to FDG PET but superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically informative than FDG PET in patients with lung cancer. However, AC PET may play a complementary role in the identification of low-grade malignancies that are not FDG avid.     

Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid myocardial single-photon mission tomography

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64±12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7±12.4 days. BMIPP myocardial SPET was carried out belote and after CoQ 10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slicesxnine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement., from 2.39±0.39 to 2.54±0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1±43, compared to 13.9±4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and alter CoQ treatment (19.2±8.1 vs 19.7±7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ 10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging.     

High and typical <Superscript>18</Superscript>F-FDG bowel uptake in patients treated with metformin

Purpose This prospective and bi-centric study was conducted in order to determine the impact of antidiabetic treatments (AD) on ¹⁸F-FDG bowel uptake in type 2 diabetic patients. Methods Fifty-five patients with previously diagnosed and treated type 2 diabetes mellitus (group 1) were divided in two subgroups: AD treatment including metformin (n=32; group 1a) and AD treatment excluding metformin (n=23; group 1b). The 95 patients without diabetes mellitus made up controls (group 2). ¹⁸F-FDG uptake in small intestine and colon was visually graded and semi-quantitatively measured using the maximum standardized uptake value. Results ¹⁸F-FDG bowel uptake was significantly increased in AD patients (group 1) as compared to controls (group 2) (p<0.001). Bowel uptake was significantly higher in AD patients including metformin (group 1a) as compared to AD patients excluding metformin (group 1b) (p<0.01), whose bowel uptake was not significantly different from controls (group 2). A metformin treatment was predictive of an increased bowel uptake in the small intestine (odds ratio OR=16.9, p<0.0001) and in the colon (OR=95.3, p<0.0001), independently of the other factors considered in the multivariate analysis. Bowel uptake pattern in the patients treated with metformin was typically intense, diffuse and continuous along the bowel, strongly predominant in the colon, in both the digestive wall and lumen. Conclusion This study emphasizes that metformin significantly increases ¹⁸F-FDG uptake in colon and, to a lesser extent, in small intestine. It raises the question of stopping metformin treatment before an ¹⁸F-FDG PET/CT scan is performed for intra-abdominal neoplasic lesion assessment.     

Myocardial metabolism of 123I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease

Purpose ¹²³I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (¹²³I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of ¹²³I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake.Methods Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6).Results Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48±19% vs 66±14%, p<0.05) and its subsequent retention (73±13% vs 85±8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0±20.0% to 15.8±9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3±21.9% to 71.3±10.1%, p<0.05).Conclusion These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight into the pathophysiology of stunned myocardium.An erratum to this article can be found at     

Comparison of [<Superscript>18</Superscript>F]FHBG and [<Superscript>14</Superscript>C]FIAU for imaging of <Emphasis Type="Italic">HSV1-tk</Emphasis> reporter gene expression: adenoviral infection vs stable transfection

Earlier studies involving comparison of different reporter probes have shown conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1--d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We hypothesized that this reported discrepancy may be related to how the reporter gene is delivered to the cells—stably transfected vs adenoviral infection. We directly compared the uptake characteristics of [¹⁸F]FHBG, [³H]PCV, and [¹⁴C]FIAU in cell culture and in vivo using an adenoviral mediated gene transfer model and stably transfected cells. We further compared the uptake of three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing cells to assess the optimal reporter probe/reporter gene combination. [¹⁴C]FIAU accumulation was greater than that of [³H]PCV and [¹⁸F]FHBG in control cells and in HSV1-tk stably transfected cells (P<0.001). After infection of C6 cells with AdCMV-HSV1-tk (1.5×10⁸ pfu), [¹⁸F]FHBG and [³H]PCV accumulation was significantly greater than that of [¹⁴C]FIAU (P<0.01). [¹⁸F]FHBG and [³H]PCV accumulated to a significantly greater extent than [¹⁴C]FIAU in C6-stb-sr39tk+ and AdCMV-HSV1-sr39tk infected C6 cells (P<0.001). Results from the nude mice supported the results in cell culture. [¹⁴C]FIAU led to significantly higher %ID/g in C6-stb-tk+ xenografts than [¹⁸F]FHBG (P<0.05); however, compared with [¹⁴C]FIAU, [¹⁸F]FHBG led to as high %ID/g in HSV1-tk expressing hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that [¹⁸F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+) for at least 4 h after injection, while it was rapidly cleared from HSV1-tk expressing cells (MH3924A-stb-tk+). [¹⁴C]FIAU accumulated in HSV1-tk stably expressing cells to a greater extent than either [³H]PCV or [¹⁸F]FHBG. However, the accumulation of [³H]PCV and [¹⁸F]FHBG in adenoviral infected C6 cells or hepatocytes was equivalent to or greater than that of [¹⁴C]FIAU. These results may be due to intracellular biochemical changes (e.g., thymidine) when cells are infected with adenovirus. For adenoviral studies, the [¹⁸F]FHBG/HSV1-sr39tk combination was shown to be more sensitive than the [¹⁴C]FIAU/HSV1-tk combination HSV1-tk.     

Prediction of functional recovery in acute myocardial infarction: Comparison between sestamibi reverse redistribution and sestamibi/BMIPP mismatch

Background  It has been known that Tc 99m sestamibi/iodine 123 betamethyliodophenylpentadecanoic (¹²³I-BMIPP) (sestamibi/BMIPP) mismatch is an indicator of viable myocardium in acute myocardial infarction (AMI). We have reported that reverse redistribution of sestamibi in AMI indicates the patency of infarct-related artery and a preserved left ventricular function in the chronic stage. In this study we investigated the relationship between reverse redistribution of sestamibi and sestamibi/BMIPP mismatch in patients with AMI. Methods  Twenty-three patients with AMI who received direct percutaneous transluminal coronary angioplasty underwent both BMIPP and sestamibi SPECT within 2 weeks after onset. Sestamibi images were obtained 1 hour (early) and 3 hours (delayed) after injection of sestamibi. BMIPP imaging was carried out 30 minutes after injection. The left ventricle was divided into 17 segments, and regional myocardial uptakes of the tracers in each segment were scored from 0 (normal) to 3 (no activity). A reverse redistribution pattern was defined as an increase of ≽1 in the regional score at the delayed images. More reduced BMIPP uptake than sestamibi uptake in each segment was determined as sestamibi/BMIPP mismatch. Contrast left ventriculography was performed soon after revascularization and repeated 1 month later. Results  Of 15 patients with sestamibi reverse redistribution, sestamibi/BMIPP mismatch was observed in 14 patients (93%), whereas mismatch was seen in only one of seven patients (14%) without reverse redistribution (p<0.01). In patients with sestamibi reverse redistribution, regional scores of BMIPP agreed with those of early and delayed images of sestamibi in 51 segments (46%) and in 92 segments (83%), respectively. In the chronic stage, both regional wall motion and left ventricular ejection fraction improved in patients with sestamibi reverse redistribution (wall motion score: 6.7±2.4 vs 2.7±2.1, p<0.01; ejection fraction: 56%±7% vs 64% ±8%, p<0.01), but not in those without reverse redistribution. Conclusion  Both reverse redistribution of sestamibi and sestamibi/BMIPP mismatch reflect the recovery of left ventricular function and thus imply myocardial viability in AMI. Because the presence of reverse redistribution of sestamibi agreed with that of sestamibi/BMIPP mismatch, additional BMIPP images can be replaced by the delayed images after a single injection of sestamibi. Supported in part by grants-in-aid for Scientific Research (nos. 08457200 and 08770488) from the Ministry of Education, Science and Culture, Japan.     

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labelled probes

Purpose  The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of ¹²³I- and ^99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. Methods  A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D₂ receptor ligand [¹²³I]IBZM and the cerebral perfusion tracer [^99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [¹²³I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [^99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP₃ receptor. Results  In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [¹²³I]IBZM and of cardiac [^99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [¹²³I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [^99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [¹²³I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. Conclusion  Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of ¹²³I- and ^99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Homocysteine levels are associated with the results of <Superscript>123</Superscript>I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

Purpose Elevated total plasma homocysteine (tHcy) levels and cardiovascular autonomic dysfunction are associated with a high mortality in type 2 diabetic patients. We tested the hypothesis that hyperhomocysteinemia is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. Methods The study group consisted of 17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58±5 years, high tHcy group). The control group consisted of 23 age-matched type 2 diabetic patients with normal tHcy levels (≤15 mmol/l, age 58±9 years, normal tHcy group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy. Results Early and delayed ¹²³I-MIBG myocardial uptake values were lower (p<0.005 and p<0.01, respectively) and the percent washout rate of ¹²³I-MIBG was higher (p<0.001) in the high tHcy group than in the normal tHcy group. The fasting plasma insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index values (p<0.0001) were higher in the high tHcy group than in the normal tHcy group. Multiple regression analysis revealed that the level of tHcy was independently predicted by the HOMA index values and the myocardial uptake of ¹²³I-MIBG at the delayed phase. Conclusion Our results demonstrate that high levels of tHcy are associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus.