Evaluation of esophageal cancers using fluorine-18-fluorodeoxyglucose PET.

UNLABELLED: To evaluate glucose metabolism in esophageal cancer, 48 patients were studied using PET with 18F-2-fluoro-2-deoxy-D-glucose (FDG). METHODS: After transmission scans were obtained, 18F-FDG (148 MBq) was administered intravenously. In 11 patients, a dynamic study was performed to evaluate glucose metabolism. Using the changes of radioactivity in both plasma and tumor, rate constants (k1-k4) defined in the metabolic model for 18F-FDG were calculated. In 48 patients, static PET scans of the tumor (5-min scans) were obtained 60 min after administration. Fluorine-18-FDG activity within each tumor was corrected for physical decay and normalized by dose administration and patient weight to produce a standardized uptake value (SUV). RESULTS: Both the k3 value (n = 11) reflecting hexokinase activity and SUV (n = 13) were well correlated with hexokinase activity from the resected specimen (p < 0.05). Forty-seven of 48 patients before treatment revealed SUV greater than 2.0, but 10 normal control subjects and 1 esophageal benign tumor revealed less than 2.0 (accuracy rate 98.3%). Although clinicopathological findings did not correlate with SUV, except for two patients with carcinosarcoma, 23 patients with an SUV greater than 7.0 had a poor prognosis compared with 25 patients with SUVs less than 7.0. CONCLUSION: These findings suggest that 18F-FDG PET may be useful in distinguishing malignant tumors from benign lesions and in the preoperative evaluation of the prognostic factor.

Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose.

BACKGROUND: Positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG) can provide quantitative information about tumor glucose metabolism. The prognostic value of this technique was evaluated for breast carcinoma patients. METHODS: FDG PET was performed on 70 patients with primary breast carcinoma, and the differential absorption ratio (DAR) was calculated as an index of FDG uptake. Overall and relapse free survival curves were created by the Kaplan-Meier method, and differences between the curves were analyzed with the log rank test. For multivariate analysis, the Cox proportional hazards regression model was used. RESULTS: The mean DAR was 2.61+/-1.61 standard deviation (range, 0.65-9.39). According to the grade of DAR, patients were then classified into high DAR (> or =3.0) and low DAR (<3.0) groups. The high DAR group had significantly worse prognoses for both overall and relapse free survival (P < 0.0005 and P < 0.0001, respectively). In multivariate analysis, DAR was an independent predictor of the relapse free survival of breast carcinoma patients (P=0.0377). CONCLUSIONS: DAR, as determined by FDG PET, may be useful as a prognostic indicator for patients with primary breast carcinoma.

Effect of the duration of fasting on myocardial fluorine-18-fluorodeoxyglucose positron emission tomography images in normal males.

To evaluate the effect of the duration of fasting on myocardial fluorine-18-fluorodeoxyglucose (FDG) uptake and distribution, 16 FDG-positron emission tomography (PET) studies were performed in 7 normal volunteers under three different conditions: glucose loading, 6 h fasting and overnight fasting. In the glucose-loaded condition, all subjects had good image quality, and myocardial metabolic rates of glucose (MRGlc) were significantly higher than those in the other two conditions. In the 6 h and overnight fasting conditions, image qualities varied according to MRGlc. Although there were visually distinct regional differences with MRGlc ranging from 0.05 to 0.15 mumol/min per g, these differences were not impressive by a quantitative analysis. The ranges of MRGlc in these two fasted conditions overlapped each other. There was a significant negative linear correlation between MRGlc and serum free fatty acid levels. Thus, MRGlc and image quality in fasted normal subjects varied with the extent of the fed-to-starved transition under clinical fasting conditions (6 h to overnight), and this transition does not depend solely on the duration of fasting. These findings may explain the heterogeneity in FDG studies under fasting conditions.

[Correlation analysis between patlak plot and DAR using 11C-methionine PET].

Seven patients were studied with positron emission tomography (PET) using 11C-methionine. All had non-Hodgkin's lymphoma but one, who had Hodgkin's disease. By assuming a simple three-compartment model for dynamic data analysis, we used the graphic method proposed by Patlak et al., where Ki (K2K3/(K1+K3)) was compared with DAR (differential absorption ratio). Trichloroacetate was added to each plasma sample, and the activity of the acid-soluble fraction was counted to eliminate the influence of the protein-bound fraction of injected activity. Patlak data plots, using this acid-soluble fraction as an input factor, showed good linearity over the time of data collection. All tumors showed clear 11C-methionine accumulation. Tumor activity reached almost a plateau within 10 min and was kept at the same level for at least 30 min. Ki and DAR were 0.070 +/- 0.035 and 4.64 +/- 1.85 (mean +/- SD), respectively. There was no apparent correlation between histological type and Ki or DAR, while the correlation efficient between Ki and DAR was 0.875. Our conclusion is that DAR will give almost the same result as dynamic data in the analysis of methionine metabolism using PET.

[Evaluation of clinical usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging].

We studied 11C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection to 11C-MET, the increase in rate of radioactivity of 11C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates.

[Evaluation of the cases of benign disease with high accumulation on the examination of 18F-fluorodeoxyglucose PET].

In this study 39 cases of abdominal benign disease were examined by PET using 18F-fluorodeoxyglucose (FDG), and 11 cases of them (i.e. 4 cases of liver abscess, 1 of pelvic abscess, 1 of omental abscess, 2 of chronic pancreatitis, 1 of inflammatory pseudotumor of liver, 1 of retroperitoneal leiomyoma and 1 of solid and cystic tumor of pancreas) which showed as high accumulation of FDG as malignant lesion were investigated of their clinical and pathological feature. We used Ci/Cp ratio as index to express the accumulation of FDG in the lesion, which was calculated from radioactivities of the lesion (Ci) and the plasma (Cp) at 60 mins after injection of FDG. The Ci/Cp ratio of the 11 cases was 3.64 +/- 0.77. The pathological feature of the 9 inflammatory cases was high accumulation of inflammatory cells and that of the 2 benign tumor cases was solid proliferation of tumor cells. The serum of the 9 inflammatory cases showed high CRP value. It was considered that the high accumulation of FDG in inflammatory lesions was due to piles of FDG uptake of the many inflammatory cells, while the 2 benign tumors of high accumulation were considered that the tumor cell had as high glucose metabolism as malignancies.

[Evaluation of gastroenterological disease by using 18F-FDG PET--differential diagnosis of malignancy from benignity].

In this study, we used 18F-FDG PET to differentiate gastroenterological malignancy from benignity. We investigated 122 patients with gastroenterological disease before treatment (with lesions exceeding 2.0 cm in diameter only). 60 min after injection of FDG, although 16 cases out of 17 benign disease did not reveal accumulation higher than normal tissue, 105 cases of malignant tumor except some of hepatocellular carcinoma revealed high accumulation of FDG. FDG uptake was expressed as the Ci/Cp ratio, calculated from radioactivity of the tumor (Ci) and the plasma (Cp). 89 cases out of 90 which show more than 2.0 of Ci/Cp ratio were malignant tumor. On the other hand, 32 cases which show less than 2.0 contained 16 cases of benign disease and 15 of hepatocellular carcinoma. FDG PET is a useful tool for differential diagnosis of malignant tumor from benign disease except some of hepatocellular carcinoma.

[Analysis of stereoisomers involved products of synthesized 18F-2-deoxy-2-fluoro-D-glucose by 1H-NMR spectroscopy].

18F-2-fluoro-2-deoxy-D-mannose (FDM) is eventually involved in side products of 18F-2-fluoro-D-glucose (FDG) synthesized by the acetylhypofluorite method. We attempted the measurement of existence ratio of FDM and FDG, FDM alpha and FDM beta, FDG alpha and FDG beta by 400 MHz 1H-NMR spectroscopy. The ratio of FDM to FDG were 4.0%. The amounts of FDG beta were much larger than those of FDG alpha. The difference between the amounts of FDM alpha and FDM beta were not significant. 1H-NMR spectroscopy could be utilized in quantitative analysis of products and byproducts in cyclotron chemicals. The FDM in FDG synthesized in our cyclotron system was not considered to affect a lot of influence in PET study.

[Can fluorodeoxyglucose-positron emission tomography evaluate the functional differentiation of hepatocellular carcinoma].

Tumor uptake of 18F-fluorodeoxyglucose (FDG) was studied by dynamic positron emission tomography (PET) in 23 cases of hepatocellular carcinoma. The metabolic rate constants, K1 to K4, were generated by non-linear least square fitting method. We confirmed that K3 from the PET study significantly correlated with directly measured hexokinase activity of the cancer tissue. The region of HCC always had higher K3 values, which represents the hexokinase activity compared with the non-cancerous region. By FDG images, however, in 50% of cases the cancer region could not be clearly defined from the surrounding noncancerous hepatic tissue. These HCC cases without accumulation of FDG had a high ratio of K4/K3 (K4 represents glucose-6-phosphatase activity), which correlated well with the inverse ratio of FDG accumulating images on PET. According to the PET images which is represented by K4/K3 and the hexokinase activity which is represented by K3, we divided these 23 cases into three groups and retrospectively compared their survival rates. The groups with high K4/K3 (greater than or equal to 0.40) had longer survival than other groups. From the view point of glucose metabolism, the value of K4/K3 calculated from dynamic studies of FDG-PET may represent the functional differentiation of HCC.

Change of cerebral glucose metabolism by antineoplastic drug.

To estimate change of cerebral glucose metabolism by anticancer drugs, positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) was performed in 11 patients with malignancies who did not show neurological symptoms. In a patient treated with intravenous high-dose methotrexate (HD-MTX) and intrathecal MTX, apparent decrease of glucose metabolism was observed. HD-MTX and intrathecal MTX may cause cerebral glucose metabolism disorder primarily. Cerebral glucose metabolism was also mildly reduced by chemotherapy with drugs other than MTX and by radiotherapy outside the brain, with a corresponding change of blood data. It may reflect a psychosomatic change in whole body.

Technetium-99m HMPAO labeled leukocytes in inflammation imaging.

Technetium-99m-HMPAO (Tc-99m-HMPAO) labeled leukocyte imaging was carried out in 19 patients at 3-5 hr after reinjection. There were no side effects noted. Tc-99m leukocyte images showed gall bladder, colon, kidney, and urinary bladder activity in normal distribution as a result of excretion of the eluted Tc-99m complex. They yielded a sensitivity of 93%, a specificity of 100% and an accuracy of 95%. They were correctly positive in 14 out of 19 cases. But one false negative case was seen in a patient with pyonephrosis showing a lack of renal function with decreased renal blood flow. It was concluded that they have some advantages over In-111 leukocyte images, but we have to consider the fact that the ureteral obstruction or the lack of renal function with decreased renal blood flow may result in a false positive or a false negative case.

The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis.

Twenty-one patients with untreated malignant lymphoma in the head and neck region were evaluated with positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) and gallium-67 SPECT imaging. Tumor-to-normal soft-tissue contrast ratios (TCRs) obtained 60 min after injection of FDG were higher than 2.6, and all malignant lymphomas were clearly visualized. In patients with poor prognosis, higher TCRs and glucose utilization rates (GURs) were observed, whereas low TCR and GUR were shown in a patient with low-grade malignancy. In comparison with 67Ga scintigraphy, patients with high TCRs and GURs were likely to show increased accumulation of gallium-67, but accumulation of gallium-67 was not increased as much as FDG in poor prognostic patients. FDG-PET may be useful in the detection and management of malignant lymphoma.

[PET assessment of myocardial viability with glucose loading and fasting FDG images].

Positron emission tomography (PET) offers the potential capability of evaluating tissue viability. We have studied the changes of myocardial F-18 deoxyglucose (FDG) uptake with glucose loading. In a fasting state (for at least 5 hours) and in a glucose loading state (50 g glucose orally one hour before the study) FDG (74-148 MBq) PET studies were performed for 50-60 minutes in 3 cases. 2 were subjects with anterior myocardial infarction (MI) including one with a ventricular aneurysm (case 1), one with a recent MI (case 2). One was a subject of aortic valvular disease without coronary lesions (case 3). Arterial input function (Ca(t)) and myocardial activity (Cm(t)) were derived from the regions of interest (ROI) on the left atrium and from multiple ROI's circumferentially about the myocardium. Net extraction, FU (Fractional Uptake) = Cm(T)/integral of T0 Ca(t)dt, were calculated. Normal segment (N) showed an increase in FU with glucose loading, but the ischemic segment showed no increase (case 1) or a lower increase (case 2) relative to N. This study shows that the increase in FU with glucose loading suggests the persistence of viable myocardium. In conclusion, myocardial viability may be evaluated by comparing FDG images in a glucose loading state with those in a fasting state.

[Fundamental study of 99mTc nanocolloids for inflammation imaging].

The biodistribution of nanometer-sized colloidal particles (nanocolloids, Solco-Basle Ltd.) was examined in six rabbits with turpentine-induced abscesses in the musculature of their hind legs. 99mTc labelled colloids with a mean particle size less than 100 nm were administered to each rabbit intravenously. The biodistribution of the tracer was studied with a gamma camera 1, 3, and 24 hours after injection. Prominent uptakes were demonstrated in the liver, spleen, bone marrow, kidneys, and urinary bladder. On the other hand, the abscess and surrounding inflammatory edema were depicted as unclearly margined faint hot spots. Subsequently, the rabbits were sacrificed and activity per gram tissues were counted with a well-type gamma counter. Although the results were almost in agreement with a gamma camera study, it was noticed the activity counts in the abscess were significantly higher than that of control muscles.

[Evaluation of the effect of treatment in patients with liver tumors using 18F-fluorodeoxyglucose PET].

To evaluate the glucose metabolism in the liver tumor, 18FDG PET (Positron Emission Tomography) was performed in 9 patients with primary and metastatic liver tumors. And usefulness of 18FDG PET in clarifying the effect of treatment on liver tumor was examined. Glucose metabolism of tumor was showed in terms of the coefficient 'C' calculated by Patlak's plot. Each tumor's coefficient 'C' was 0.016-0.054 and it decreased after treatment. Compared with pathological findings, the coefficient 'C' of necrosis part of tumor was 0.004 and fibrous change after irradiation was 0.007. It suggested that coefficient 'C' reflected activity of tumor and it was a useful index to know viability of tumors in the treatment for patients with liver tumors.

The complementary role of indium-111 labeled leukocyte imaging, ultrasonography and computed tomography in the evaluation of postoperative infection or abscess.

We report our experiences with the combined use of indium-111 labeled leukocyte imaging (In-III WBC scan.), computed tomography (CT) and ultrasonography (US) for evaluation of suspected postoperative infection or abscess, and discuss the complementary roles of these modalities. Postoperative abscesses or infections were diagnosed in 9 of 20 patients. All patients were correctly diagnosed by In-111 WBC imaging and 4 patients could not be diagnosed by US because of bowel gas. One false-positive CT examination and another artifact on CT images due to respiratory movements were obtained. The three modalities were found to be complementary: CT and US were efficient imaging methods for diagnosis and treatment of abscess. In-111 WBC imaging could estimate the activity of inflammation.