Myocardial metabolism of 123I-BMIPP during low-flow ischaemia in an experimental model: comparison with myocardial blood flow and 18F-FDG.

Risk stratification of coronary artery disease may provide a basis for selection of treatment to prevent myocardial events and to assist functional recovery. Iodine-123 (rho-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is a radioiodinated fatty acid analogue for single-photon emission tomographic (SPET) imaging, and several reports have demonstrated that the abnormal uptake of 123I-BMIPP is associated with wall motion abnormality and severe coronary artery stenosis. Clarification of the contribution of fatty acids to myocardial metabolism would be highly valuable in recognising this critical condition. In this study, we investigated the myocardial uptake of 123I-BMIPP under low-flow ischaemia, and compared it with the uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). Using open chest dogs, the flow of the left anterior descending coronary artery was controlled using a pneumatic occluder in order to maintain a 30%-40% reduction of Doppler flow. 123I-BMIPP and 18F-FDG were injected into the left atrium after 90 min of ischaemia (protocols 1 and 3). Canine hearts were excised after 120 min of ischaemia for the measurement of radioactivity. In protocol 2, 123I-BMIPP alone was injected and hearts were excised 8 min after the injection. A time-course biopsy study was also performed at the same time (protocol 3). Wall thickening was evaluated using a wall tracker module. The uptake of 18F-FDG increased significantly in the ischaemic region (232%+/-135% vs non-ischaemic, P<0.05 in protocol 1) even on mild reduction of myocardial blood flow (MBF). The increased uptake of 18F-FDG did not correlate well with the severity of MBF. On the other hand, 123I-BMIPP uptake decreased gradually (78.9%+/-23.6%, P<0.05 in protocol 1, and 85.9%+/-24.3% in protocol 2) in the ischaemic region, specifically in the endocardium (64.0%+/-28.9%, P<0.05 in protocol 1, and 75.1%+/-28.8%, P<0.05 in protocol 2), and correlated strongly with MBF (r=0.93 in protocol 1 and r=0.97 in protocol 2) as a logarithmic function. This indicated that the abnormal uptake of 123I-BMIPP was associated not only with wall motion abnormality but also with the severity of MBF. In the biopsy study (protocol 3), the radioactivity of either 123I-BMIPP or 18F-FDG correlated well with the MBF at the time of tracer injection and was similar to post-mortem analysis. It is concluded that 18F-FDG is a valid tool for identifying ischaemic myocardium even in its earliest stages. On the other hand, 123I-BMIPP might be used to detect moderately to severely ischaemic myocardium such as hibernation, suggesting the potential value of 123I-BMIPP in the risk stratification of patients with severe coronary artery disease who require revascularisation without delay.

Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors.

The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions.

Iodinated free fatty acid and 201T1 uptake in chronically hypoperfused myocardium: histologic correlation study.

UNLABELLED: 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is a tracer for the evaluation of ischemic heart disease. The purpose of this study was to assess the relationship between 1231-BMIPP uptake and myocardial fibrosis. METHODS: Fifteen patients who underwent cardiac surgery were examined by imaging with 201TI and 123I-BMIPP, and histologic specimens were taken during surgery. The relative uptake of 201TI (%TI) and that of 123I-BMIPP (%BMIPP) were calculated. The percentage of fibrosis (%fibrosis) was analyzed with the specimen. RESULTS: %TI correlated strongly with %fibrosis (r = -0.94; P < 0.001). %BMIPP also correlated significantly with %fibrosis (r = -0.88; P < 0.001), but the change in %BMIPP looked biphasic. In the category of only mild fibrosis, %BMIPP showed a steep decrease. 123I-BMIPP-201TI mismatch was found only for fibrosis <20%. CONCLUSION: 123I-BMIPP gave specific information about metabolic changes that occurred in ischemic myocardium without severe fibrotic changes.

Technetium-99m-labeled medium-chain fatty acid analogues metabolized by beta-oxidation: radiopharmaceutical for assessing liver function.

External imaging of energy production activity of living cells with 99mTc-labeled compounds is a challenging task requiring good design of 99mTc-radiopharmaceuticals. On the basis of our recent findings that 11C- and 123I-labeled medium-chain fatty acids are useful for measuring beta-oxidation activity of hepatocytes, we focused on development of 99mTc-labeled medium-chain fatty acid analogues that reflect beta-oxidation activity of the liver. In the present study, monoamine-monoamide dithiol (MAMA) ligand and triamido thiol (MAG) ligand were chosen as chelating groups because of the stability and size of their complexes with 99mTc and their ease of synthesis. Each ligand was attached to the omega-position of hexanoic acid (MAMA-HA and MAG-HA, respectively). In biodistribution studies, [99mTc]MAMA-HA showed high initial accumulation in the liver followed by clearance of the radioactivity in the urine. Analysis of the urine revealed [99mTc]MAMA-BA as the sole radiometabolite. Furthermore, when [99mTc]MAMA-HA was incubated with living liver slices, generation of [99mTc]MAMA-BA was observed. However, [99mTc]MAMA-HA remained intact when the compound was incubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of beta-oxidation. The findings in this study indicated that [99mTc]MAMA-HA was metabolized by beta-oxidation after incorporation into the liver. On the other hand, poor hepatic accumulation was observed after administration of [99mTc]MAG-HA.

Evaluation of radioiodinated medium chain fatty acids as new diagnostic agents for the determination of hepatic viability.

Radiopharmaceuticals which reflect beta-oxidation in hepatocytes will provide useful information on the prognosis after surgery or on the efficacy of treatment, since beta-oxidation is the main pathway responsible for adenosine triphosphate in hepatocytes. We have previously developed [1-11C]octanoate as a diagnostic agent for determination of hepatic viability by means of positron emission tomography (PET). The goal of the present study was to develop a new radiopharmaceutical for single-photon emission tomography (SPET), which has the advantage of being more widely used than PET. To this end, two radioiodinated omega-(4-iodophenyl)-medium chain fatty acids, p-iodophenylvaleric acid (IPVA) and p-iodophenylenanthic acid (IPEA), were synthesized and evaluated as radiopharmaceuticals for determination of hepatic viability. Metabolite analyses in vitro and in vivo and a biodistribution study in normal mice indicated that both compounds were taken up by the liver actively and metabolized by beta-oxidation. However, these studies also indicated that IPEA is more suitable as an imaging agent than IPVA. Based on these results, SPET imaging studies were performed in normal and hepatitis model rats using [123I]IPEA. The time-activity curves of the liver showed two-phase clearance of radioactivity in both normal and hepatitis model rats, but the clearance was delayed depending on the severity of hepatitis. Furthermore, the clearance rate of the first phase was correlated with the ATP level in hepatocytes, which was used as an index of the energy production capacity of hepatocytes. In conclusion, IPEA was metabolized predominantly by beta-oxidation, and the clearance of IPEA from the liver was closely associated with the ATP concentration in the liver. Thus, [123I]IPEA is a potentially useful new radiopharmaceutical for diagnosis of hepatic viability based on energy metabolism.

Glucose transporter protein-independent tumor cell accumulation of fluorine-18-AFDG, a lipophilic fluorine-18-FDG analog.

UNLABELLED: Fluorine-18-fluorodeoxyglucose (FDG) is used clinically for tumor diagnosis, but its mechanism of accumulation in tumor cells is complicated because two factors, glucose transporter protein (GLUT) and hexokinase, govern [18F]FDG uptake directly. We selected a lipophilic [18F]FDG analog, 1,3,4,6-tetra-acetyl-2-[18F]-2-deoxy-D-glucose ([18F]AFDG), to regulate the effects of hexokinase and evaluated its characteristics in an in vitro cell culture system. METHODS: Fluorine-18-AFDG was synthesized by the method used to produce [18F]FDG, as an intermediate of [18F]FDG. Fluorine-18-AFDG uptake study was performed with LS180 tumor cells, and its metabolites were also investigated by thin-layer chromatography. To evaluate the relationship between [18F]AFDG and GLUT, we also examined [18F]AFDG uptake in the presence of cytochalasin B or with increased medium glucose concentration. The effects of lowered temperature (4 degrees C) on [18F]AFDG uptake were also investigated. RESULTS: Fluorine-18-AFDG (lipophilicity: octanol/water = 3.5) uptake was 3.3-fold higher than that of [18F]FDG. Metabolic analysis showed that [18F]AFDG was extremely stable in the incubation medium but was quickly hydrolyzed and metabolized to 2-fluoro-[18F]-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6P) in tumor cells. Fluorine-18-FDG-6P accounted for approximately 45% of the total radioactivity after a 60-min incubation of [18F]AFDG. Incubation with 50 microM cytochalasin B did not affect [18F]AFDG uptake. In medium with double the control glucose level, [18F]FDG uptake was decreased by about 50%, but [18F]AFDG uptake was not affected. Fluorine-18-AFDG uptake and [18F]FDG-6P production did not show saturation and increased linearly with addition of a 10-fold higher concentration of [18F]AFDG. Lowered incubation temperature caused decreased [18F]AFDG uptake due to reduced [18F]FDG-6P production. CONCLUSION: Fluorine-18-AFDG rapidly penetrated the cell membrane as a result of its high lipophilicity and was metabolized to [18F]FDG-6P within cells. Fluorine-18-AFDG was thus characterized as "GLUT-independent [18F]FDG."

Synthesis and characterization of radioiodinated (S)-5-iodonicotine: a new ligand for potential imaging of brain nicotinic cholinergic receptors by single photon emission computed tomography.

(S)-5-Iodonicotine (4a), an (S)-nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by single photon emission computerized tomography (SPECT). [125I]-(S)-Iodonicotine ([125I]-4a) was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC). The binding affinity of 4a for brain nicotine receptors was measured in terms of displacement of [3H]cytisine from binding sites in rat cortical membranes. The binding data revealed that the affinity of 4a was the same as that of (S)-nicotine and 80-fold higher than that of the (R)-enantiomer (4b). Biodistribution studies in mice disclosed that the brain uptake of [125I]-4a was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125I]-4a was dense in the thalamus, intermediate in the cortex and striatum, and less marked in the cerebellum. Furthermore, the administration of (S)-nicotine reduced the uptake of [125I]-4a in the thalamus and resulted in a nearly identical level of radioactivity in the cerebellum. [125I]-(R)-5-Iodonicotine ([125I]-4b) showed more rapid washout from the brain and a less extensive regional cerebral distribution than the (S)-enantiomer ([125I]-4a). Thus, 4a bound to brain nicotine receptor in vivo, and therefore iodine-123-labeled 4a may be a potential radioligand for use in vivo cerebral nicotinic receptor studies by SPECT.

Extraction and retention of technetium-99m-ECD in human brain: dynamic SPECT and oxygen-15-water PET studies.

UNLABELLED: The kinetic behavior of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in the human brain was investigated in six normal volunteers. METHODS: Dynamic SPECT and a three-compartmental model were used to estimate the rate constants of 99mTc-ECD in normal human brain. Extraction fraction (E), retention fraction (R) and permeability surface area product (PS product) of 99mTc-ECD were calculated using the rate constants. Regional cerebral blood flow (rCBF) was measured by PET with 15O-water. RESULTS: The rate constants in the cerebral cortex were estimated as 0.307 +/- 0.021 for K1 (influx constant), 0.201 +/- 0.047 for k2 (backdiffusion rate constant), 0.547 +/- 0.103 for k3 (lipophilic-to-hydrophilic conversion constant) and 0.0028 +/- 0.0012 for k5 (rate constant from lipophilic compartment to blood) at rCBF of 0.509 +/- 0.055 ml/g/min (mean +/- s.d.). The first-pass extraction, retention fraction and PS product were calculated as 0.608 +/- 0.069, 0.734 +/- 0.047 and 0.477 +/- 0.060, respectively. The first-pass extraction of 99mTc-ECD decreased significantly with increases in rCBF. The retention fraction and PS product of 99mTc-ECD did not show significant changes within the normal range of rCBF. The net extraction of 99mTc-ECD calculated from the static SPECT image obtained from 20 to 40 min was 0.358 +/- 0.039 in the cortex. CONCLUSION: Technetium-99m-ECD has a fairly high brain extraction, and its retention fraction and PS product appear to be independent of rCBF in the healthy human brain.

Nonlinearity correction of brain perfusion SPECT based on permeability-surface area product model.

UNLABELLED: It is well known that many cerebral perfusion tracers underestimate cerebral blood flow in high flow range. A model has been proposed to correct nonlinear relationship of flow and uptake of the tracers that accounts for the permeability-surface area product (PS model). METHODS: We examined 43 patients in this study. To test the feasibility of this method for 123I-IMP, 99(m)Tc-HMPAO and 99(m)Tc-ECD, radioactivity ratios of cerebral regions to cerebellum (C/Cr) on SPECT images were compared with those of rCBF (F/Fr) measured by PET using the 15O CO2 steady-state method. Coefficient for correction in the PS model was estimated by the least squares method, and SPECT data were corrected using these coefficients. RESULTS: Estimated PS value by this method was highest in IMP (116 ml/min/100 g) followed by ECD (66 ml/min/100 g) and HMPAO (46 ml/min/100 g). The corrected SPECT data demonstrated an excellent linear relationship, which was close to unity, with rCBF. CONCLUSION: These results indicate that the PS model can be used for nonlinearity correction of brain perfusion SPECT.

FDG-PET evaluation of therapeutic effects on VX2 liver tumor.

UNLABELLED: Transplanted VX2 liver tumor in the rabbit is an experimental liver tumor model in which 18F-2-fluoro-2-deoxy-D-glucose (FDG) accumulates to a 3.5-fold level that surrounds normal liver tissue. In this study, changes in FDG uptake were assessed in this liver tumor model after transcatheter arterial embolization (TAE) and radiotherapy. METHODS: Fifteen rabbits bearing VX2 liver tumors were treated with TAE with gelatin sponges 1 day before the FDG study, and 18 rabbits received local irradiation with electron beams at a dose of 12-36 Gy 1-10 days before the FDG study. In the FDG study, serial arterial blood sampling was performed to determine arterial input (AI), and 1 hr after tracer injection, normal liver tissue and tumor tissue were excised to measure radioactivity. The tumor FDG level per AI and the tumor-to-normal liver ratio were assessed. Dynamic PET images were obtained in 20 of the 46 rabbits. RESULTS: Tumor FDG uptake was significantly decreased 1 day after TAE (from 3.54 to 0.83 in the tumor-to-normal liver ratio) and 5 days after 30 Gy of irradiation (from 3.54 to 1.28). The decrease in tumor FDG uptake was dose-dependent, especially in the relatively low dose range (12-24 Gy). The untreated tumors could be clearly distinguished from the surrounding normal liver tissue, while the embolized tumors or the irradiated tumors were not clearly delineated. Histological analysis showed that the decrease in tumor FDG after treatment agreed well with the decrease in number of viable tumor cells. CONCLUSION: The VX2 liver tumor is an appropriate experimental tumor model for evaluating the change in FDG uptake in various therapeutic modalities. Moreover, the therapeutic effects can be assessed 1 day after TAE and 5 days after irradiation. Further clinical trials for the early evaluation of therapeutic effects on liver tumors using FDG-PET are warranted.

Cholinergic projection from the basal forebrain and cerebral glucose metabolism in rats: a dynamic PET study.

To investigate the influence of cholinergic projections from the basal forebrain on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic acid (BPA), and compared the results with those obtained after lesioning the basal forebrain with ibotenic acid, as well as with those from a sham-operated control group. CMRGlu was measured using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3 (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA-injected side and in the ibotenic acid-treated group, whereas K1 (transport rate of FDG from the plasma to brain) showed no marked changes. At 3 weeks postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered to levels similar to those of the sham-operated group. The main difference between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on the side contralateral to the operation in the former, while such reduction was confined to the ipsilateral hemisphere in the latter. The present results indicate that the cholinergic system in the basal forebrain regulates cerebral cortex glucose metabolism through direct excitation of cortical neurons.

Application of [125I] (S)-5-iodonicotine, a new radioiodinated ligand, in the assay of nicotinic acetylcholine receptor binding in the brain.

[125I](S)-5-Iodonicotine was prepared and its application in the assay of nicotinic acetylcholine receptor binding in the brain was studied. [125I](S)-5-Iodonicotine bound to the rat cortical membrane with high affinity (Kd, 15.0 nm). Various nicotinic cholinergic compounds showed competition with [125I](S)-5-iodonicotine for the binding sites in the rats cortical membrane, and the specificity of its binding was correlated well with that of [H3] cytisine (r = 0.98). These findings suggest that [125I](S)-5-iodonicotine binds to the same sites as [H3] cytisine and indicate that [125I](S)-5-iodonicotine can be applied as a brain nicotine receptor binding assay.

In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG-PET.

UNLABELLED: The present study was designed to assess glucose metabolism in hepatocellular carcinoma (HCC) with PET and [18F]fluorodeoxyglucose (FDG) and to compare the results with the measured in vitro enzymatic activity of glucose metabolism and the histologic grading of HCC. METHODS: Dynamic FDG-PET scans were obtained in 17 preoperative patients with HCC. From the serial tissue and arterial radioactivities obtained by dynamic PET, FDG kinetic rate constants (K1 to k4) were obtained. The standardized uptake value (SUV) was also determined from the images acquired 48 to 60 min after FDG administration. These PET results were compared with hexokinase and glucose-6-phosphatase (G6Pase) activities and histologic grading of HCC in surgically resected tumor materials. According to histologic grading, the tumors were divided into low-grade and high-grade HCCs. RESULTS: The k3 and SUV of high-grade HCCs were significantly higher than those of low-grade HCCs (p < 0.005, each). In addition, high correlations were observed between the hexokinase activities and these two parameters (r = 0.715 0.768, respectively). In some HCCs, relatively high G6Pase activities and k4 values modified tumor FDG uptake. CONCLUSION: FDG PET is a valuable method for assessing glucose metabolism and histologic grading of HCC.

Initial clinical experiences with dopamine D2 receptor imaging by means of 2'-iodospiperone and single-photon emission computed tomography.

Dopamine D2 receptor imaging was performed with 123I labeled 2'-iodospiperone (2'-ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with idiopathic Parkinson's disease, 2 with parkinsonism, 1 with Wilson's disease and 2 with pituitary tumor, and the results were compared with the data for 9 normal subjects. Following an intravenous injection of 123I-2'-ISP, early (within 30 min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi-detector SPECT scanner or a rotating gamma camera. In normal subjects, early SPECT images demonstrated uniform distribution of radioactivity in the cerebral gray matter and cerebellum reflecting regional cerebral blood flow, whereas late SPECT images showed high radioactivity only in the basal ganglia. All the patients with Parkinson's disease also demonstrated symmetrical basal ganglia uptake in the late SPECT images, but it was diminished in parkinsonism and Wilson's disease. One patient with a growth hormone-producing pituitary tumor had a positive uptake in the tumor. These preliminary clinical data demonstrated that 2'-ISP can be used for SPECT imaging of D2 dopamine receptors and may be of clinical value for the diagnosis and planning of the treatment of neurological diseases.

Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: comparison with CT and US.

PURPOSE: To assess the clinical value of positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US was performed in 40 patients. Images were independently interpreted and compared with the histopathologic findings at surgery (41 patients) or with clinical follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in 31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no increased FDG uptake (specificity = 82%). Specificities of the other modalities were lower. False-positive findings were obtained in a case of chronic active pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides "biochemical" information, is accurate in identifying pancreatic carcinoma and may be a method of choice when imaging equivocal masses detected with other "anatomic" imaging studies.

Value of fluorine-18-fluorodeoxyglucose and thallium-201 in the detection of pancreatic cancer.

UNLABELLED: This study compares the diagnostic value of 18F-FDG PET imaging and 201TI-SPECT imaging in patients with pancreatic cancer. METHODS: Twenty-five patients with histologically-proven pancreatic cancer were studied. Following PET transmission scanning, 3 mCi of 201TI were administered after patients had fasted overnight. Thallium-201-SPECT images were obtained 15 min later. Immediately after 201TI-SPECT imaging, 4 mCi of FDG were administered and PET images were obtained 60 min later. The PET and SPECT images were compared qualitatively and quantitatively. For quantitative analysis, 10 x 10 mm2 regions of interest (ROIs) were selected in areas of the tumor showing the highest tracer accumulation and in the normal pancreas. The tumor to nontumor activity ratio (T/N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 16 patients, PET identified eight additional patients in whom 201TI-SPECT images did not visualize any lesion. Thus, FDG-PET provided significantly higher sensitivity (96%) than 201TI-SPECT (64%). Among the patients showing increased tracer accumulation, the T/N ratio was significantly higher with FDG-PET (3.24 +/- 1.27) than with 201TI-SPECT (1.77 +/- 0.37) (p < 0.0001). CONCLUSION: We conclude that FDG-PET has a larger clinical value for noninvasive detection of pancreatic cancer than 201TI-SPECT. If a PET camera is available, FDG-PET is considered to be the method of choice for the evaluation of patients with suspected pancreatic cancer.

Value of fluorine-18-FDG-PET to monitor hepatocellular carcinoma after interventional therapy.

METHODS: Thirty-two tumors in 30 patients with hepatocellular carcinoma (HCC) were studied preoperatively using PET with 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) to evaluate the metabolic activity of the lesions after interventional therapy. All patients had received transcatheter arterial chemoembolization therapy using iodized oil (Lipiodol, Laboratoire Guerbet, Alnaysous-Bois, France) before the PET study. The tumors were 2 to 18 cm in diameter. FDG uptake at 48 to 60 min after tracer injection was used to determine the standardized uptake value (SUV). The SUVs of the tumor and nontumor regions of the liver were calculated to obtain the tumor-to-nontumor ratio (SUV ratio). The PET results were compared with the findings of CT and histologic examination. RESULTS: The tumors were divided into three types, consisting of those with increased FDG uptake (SUV ratio of 1.07-2.66, Type A, n = 19), similar FDG uptake to the surrounding nontumor region (SUV ratio of 0.77-1.04, Type B, n = 7) and decreased or absent FDG uptake (SUV ratio of 0.13-0.58, Type C, n = 6). In histologic examination, viable HCC tissue remained in all Type A and B tumors, whereas more than 90% necrosis was found in the Type C tumors, indicating that interventional therapy had been effective. These PET findings reflected tumor viability more accurately than the extent of intratumor Lipiodol retention on CT images. CONCLUSION: FDG-PET appears to be a valuable method for the assessment of tumor viability after interventional therapy for HCC.

Optimal dose of injection in activation study with O-15 water and PET.

In activation studies with the bolus method for O-15 water and PET, the radiotracer concentration may reach the limits of the system in terms of dead time correction and accidental coincidence. To obtain the optimal injection dose of O-15 water, we performed a normal volunteer study to evaluate the relationship between the injected dose and the radioactivity concentration in the brain and a phantom study to evaluate the performance of the PET scanner (PCT3600W) under high count rate conditions and the effect of averaging on the signal to noise ratio for the PET images. A linear relationship was noted between the injected dose (normalized for each body weight: x) and the mean radiotracer concentration in the brain measured by PET (y) (y = 2.52 + 30.1 x, n = 64, r = 0.87, p < 0.001). The percent error in the measurement of radioactivity with PET was within +/- 5% in the 100 to 2000 nCi/ml (3.7-74 KBq/ml) range. Below 100 nCi/ml (3.7 KBq/ml), the percent error increased due to the rapid increase in noise in the reconstructed images. Over 1000 nCi/ml (37 KBq/ml), on the other hand, the noise was almost unchanged. With our PET scanner, the optimal range of the radiotracer concentration in the brain is below 1000 nCi/ml (37 KBq/ml), corresponding to an injection dose of 33 mCi (1.22 GBq)/60 kg body weight. With the same total dose, the increment of number of repeated measurements for averaging provided the better signal to noise ratio. In designing a paradigm for an activation PET study, the injection dose and the number of repeated measurements for averaging should be considered.

Effects of hyperglycemia on FDG uptake in human brain and glioma.

UNLABELLED: This study evaluates the effects of hyperglycemia on fluorodeoxyglucose (FDG) uptake in the human brain and in brain tumors. METHODS: We performed glucose loading during FDG PET studies in nine patients with brain tumors (eight gliomas and one brain metastasis) and one with resected glioma. Two FDG PET scans were obtained in all cases within 1 wk in a control state and with glucose loading by intravenous infusion of 10% glucose solution. Serial arterial blood sampling was performed in all cases to obtain fractional uptake of FDG normalized by the plasma integral uptake of radioactivity (FU). RESULTS: In all nine patients with brain tumors, the tumor was depicted more clearly with glucose loading than in the control state. Glucose loading decreased FU in the cerebral cortex (54.2% +/- 13.8%) nearly in inverse proportion to the plasma glucose level, while the tumors showed a decrease (42.5% +/- 15.6%), resulting in an increased tumor-to-cortex ratio by 26.0% +/- 5.7%. Fractional uptake in the cerebellum, white matter and the edematous area also decreased by glucose loading (53.9% +/- 13.2%, 49.6% +/- 10.3% and 34.9% +/- 9.6%, respectively). CONCLUSION: These results demonstrate the different effects of hyperglycemia on normal brain tissue and on tumor, suggesting that glucose loading may be a valuable adjunct to FDG PET to enhance detection of recurrent or residual brain tumors.