Nicotinic acetylcholine receptors expressed in the ventralposterolateral thalamic nucleus play an important role in anti-allodynic effects.

BACKGROUND AND PURPOSE: Much interest is currently being focused on the anti-nociceptive effects mediated by nicotinic acetylcholine (nACh) receptors, including their location and mechanism of action. The purpose of this study was to elucidate these issues using 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA), a nACh receptor agonist, and [(125)I]5IA. EXPERIMENTAL APPROACH: We partially ligated the sciatic nerve of Sprague-Dawley rat to induce neuropathic pain [Seltzer's partial sciatic nerve ligation (PSL) model]. We then examined the changes in nACh receptor density in the CNS using [(125)I]5IA autoradiography and the involvement of nACh receptors in anti-nociceptive effects in the region where changes occurred. KEY RESULTS: Autoradiographic studies showed that the accumulation of [(125)I]5IA and the number of nACh receptors in the thalamus of PSL rats were increased about twofold compared with those in the sham-operated rats. No change was observed in other brain regions. Rats injected in the ventral posterolateral thalamic nucleus (VPL) with 5IA demonstrated a significant and dose-dependent anti-allodynic effect and this effect was completely antagonized by mecamylamine, injected with 5IA, into the VPL. The blockade of nACh receptors in the VPL by mecamylamine decreased by 70% the anti-allodynic effect of 5IA, given i.c.v. Moreover, mecamylamine given intra-VPL by itself, induced significant hyperalgesia. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that the nACh receptors expressed in the VPL play an important role in the anti-allodynic effects produced by exogenous and endogenous agonists.

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.

Effect of steroids on [18F]fluorodeoxyglucose uptake in an experimental tumour model.

BACKGROUND: It is well known that blood glucose level affects the uptake of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in tumours. Thus, the action of steroids on glucose metabolism may alter blood glucose levels and may affect FDG uptake in tumours in patients treated with steroids. To clarify this point, we determined the effects of steroids on FDG uptake in tumours in a rat model of a malignant tumour. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. They were fasted overnight and divided into three groups (n=5 in each group): (1) dexamethasone (DEX) pretreated (0.8 mg.kg(-1) body weight, i.m. injection 4 h before FDG i.v. injection); (2) prednisolone (PRE) pretreated (8 mg.kg(-1) body weight, i.m. injection 20 h before FDG i.v. injection); and (3) control (untreated) groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. FDG uptake in the tumour was expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). RESULTS: DEX and PRE pretreatments significantly increased the blood glucose levels to 128% and 145% of the control value. The levels of FDG uptake in the tumour were not significantly affected by DEX and PRE pretreatment (90% and 87% of the control value, respectively) (P=NS). CONCLUSIONS: These results demonstrate that FDG uptake in the tumour was not affected by pretreatment with steroids, in spite of a slight elevation in blood glucose level.

Value and limitation of myocardial fluorodeoxyglucose single photon emission computed tomography using ultra-high energy collimators for assessing myocardial viability.

Single photon emission computed tomography (SPECT) using ultra-high energy collimators permits wide clinical application of (18)F-fluorodeoxyglucose (FDG) imaging without the use of expensive positron emission tomography (PET) cameras. This study was designed to evaluate the value of FDG SPECT using ultra-high energy collimators in assessing myocardial viability compared with FDG PET on a regional basis. We prospectively studied 33 patients with ischaemic heart disease. The patients were injected with 555 MBq of FDG under a hyperinsulinaemic glucose clamp, and FDG PET was performed 40 min later. FDG SPECT using ultra-high energy collimators was performed immediately after FDG PET. The images of the left ventricular myocardium were divided into nine segments and the regional defect score was assessed visually using a four-point scale (0=normal to 3=defect). Regional FDG uptake (%uptake) was quantitatively analysed using polar maps. In 297 segments of all the 33 patients, agreement between the defect scores based on FDG SPECT images and those based on FDG PET images was 70%, and agreement within one rank was 96% (kappa value=0.52). The %uptake based on FDG SPECT images significantly correlated with that based on FDG PET images (r=0.77, P<0.01). However, the defect scores in the inferior wall based on FDG SPECT images were higher (1.41+/-1.14) than those based on FDG PET images (1.06+/-1.12, P<0.01). When the viable region is defined as %uptake > or =50% in FDG PET studies, the optimal cut-off level of %uptake based on FDG SPECT images was 60% in the anterior wall, apex, septum and lateral wall (accuracies, 97%, 93%, 96% and 99%, respectively), and 45% in the inferior wall (accuracy, 99%). It is concluded that FDG SPECT using ultra-high energy collimators can be used for the assessment of myocardial viability as accurately as FDG PET. However, a slight difference was observed in the defect scores mainly due to attenuation in the inferior wall. Therefore, a slightly different cut-off level for assessing myocardial viability should be applied to the inferior wall when using FDG SPECT.

Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading.

The expression of glucose transporters (GLUTs) and its relationship to fluorodeoxyglucose accumulation in malignant tumours have been well investigated, while such a relation has not been studied in inflammatory lesions. The aim of the present study was to investigate the effects of insulin and glucose loading on the expression of GLUTs in inflammatory lesions and compare them with those in malignant tumours in relation to fluorodeoxyglucose accumulation. All tissue specimens used in this study were obtained in our previous study, in which rats were inoculated with allogenic hepatoma cells (KDH-8), Staphylococcus aureus, or turpentine oil into the left calf muscle and divided into three subgroups: insulin loaded, glucose loaded, and control groups. The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the lesions (n=5-6, for each group). In all control groups, the expression levels of GLUT-1 and GLUT-3 were significantly higher than those of GLUT-2, GLUT-4 and GLUT-5. Insulin loading did not significantly affect the expression levels of GLUT-1 and GLUT-3 in these lesions except for a significant but slight decrease in the GLUT-1 expression level in the inflammatory lesion of non-infectious origin (89% of the control value). Glucose loading significantly decreased the expression level of GLUT-1 in the inflammatory lesion of non-infectious origin (70% of the control value, P<0.01), and that of GLUT-3 in the inflammatory lesion of infectious origin (70% of the control value, P<0.05), while the expression levels of GLUT-1 and GLUT-3 in the tumour were not significantly affected. These results demonstrate the effects of insulin and glucose loading on the expression level of a molecule (GLUT proteins). The decreased GLUT-1 and GLUT-3 expression levels induced by glucose loading may partly explain the impaired FDG uptake observed in our previous study.

FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models.

UNLABELLED: Although FDG uptake is closely related to the expression of the glucose transporter (GLUT) in malignant tumors, such a relationship has not been fully investigated in inflammatory lesions. The aim of our study was to determine the expression of GLUT subtypes in experimental inflammatory lesions and to compare the results with those in malignant tumors in relation to FDG accumulation. METHODS: Rats were inoculated with a suspension of Staphylococcus aureus or allogenic hepatoma cells (KDH-8) into the left calf muscle. Five days after S. aureus inoculation (n = 9) and 14 d after KDH-8 inoculation (n = 11), [(14)C]FDG was injected intravenously and its accumulation in the infectious and tumor tissues was determined as the percentage activity of the injected dose per gram of tissue (%ID/g). The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the infectious tissues (n = 6) and the tumor tissues (n = 6). Immunohistochemical grading was assessed semiquantitatively by 5 observers. RESULTS: The [(14)C]FDG uptake was significantly higher in the tumor lesion than in the inflammatory lesion (2.04 +/- 0.38 %ID/g vs. 0.72 +/- 0.15 %ID/g; P < 0.0001). The tumor and inflammatory tissues highly expressed GLUT-1 and GLUT-3. The GLUT-1 expression level was significantly higher in the tumor tissue than in the inflammatory tissue (P < 0.05). CONCLUSION: The results based on our models showed a high FDG uptake and high GLUT-1 expression level not only in the tumor lesion but also in the inflammatory lesion. The higher GLUT-1 expression level in the tumor lesion may partially explain the higher FDG accumulation in the tumor than in the inflammatory lesion.

Effects of insulin and glucose loading on FDG uptake in experimental malignant tumours and inflammatory lesions.

Fluorine-18 2-deoxy-2-fluoro-D-glucose (FDG) accumulation in tumours has been well investigated, but much less is known regarding FDG accumulation in inflammatory lesions. In this study, we determined the effects of hypo- and hyperglycaemia on FDG uptake in inflammatory lesions of infectious and non-infectious origin and compared them with those in malignant tumours in rats, to provide a biological basis for differentiating malignant lesions from benign lesions by means of FDG-PET. Rats were inoculated with a suspension of allogenic hepatoma cells (KDH-8) or Staphylococcus aureus, or with turpentine oil into the left calf muscle. Two weeks after KDH-8 inoculation and 1 week after S. aureus and turpentine oil inoculations, the rats were divided into three subgroups: insulin-loaded (2 U/kg body weight, i.p.), glucose-loaded (1.2 g/kg body weight, p.o.) and control groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. Intraperitoneal injection of insulin and oral administration of glucose induced hypoglycaemia and hyperglycaemia, respectively. In the control animals, tumours showed a level of FDG uptake which was 2.2 and 3.0 times higher than the levels in the inflammatory lesions induced by S. aureus and turpentine oil, respectively (P<0.0001). There was no significant difference in the level of FDG uptake between the two inflammatory lesions of infectious and non-infectious origin. Insulin loading significantly decreased the level of FDG uptake in tumours and in both types of inflammatory lesion to approximately one-half of the control values (P=0.001 in the tumour group and P<0.0001 in the two inflammatory lesion groups). In the glucose-loaded group, the level of FDG uptake in both types of inflammatory lesion decreased significantly to 50%-61% of the control value (P=0.0002 in the S. aureus group and P<0.0001 in the turpetine group), while the tumour uptake did not decrease significantly (86% of the control value) (P=NS). It is concluded that FDG uptake in both types of inflammatory lesion was significantly impaired in rats with hyperglycaemia induced by glucose loading, while tumour uptake of FDG was not significantly affected. These results indicate that glucose loading has greater effects on FDG uptake in inflammatory lesions than in tumours, providing a biological basis for differentiation of malignant lesions from benign lesions by FDG-PET in a clinical setting.

Clinical roles of perfusion and metabolic imaging.

Noninvasive assessment of regional myocardial perfusion is clinically important for early and accurate diagnosis of coronary artery disease. In addition, persistent metabolic alterations are often seen in post ischemic dysfunction after recovery of blood flow. Thus, prior ischemic insult may be identified as areas of altered metabolism despite normal perfusion (so-called ischemic memory imaging). Radionuclide imaging has great advantages over other imaging techniques based on the variety of radiopharmaceutical agents to probe regional cellular functions and biochemistry in vivo. Technetium-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with electrocardiogram-gated acquisition. Positron emission tomography (PET) enables metabolic assessment in vivo. Preserved fluorodeoxyglucose (FDG) uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently, iodine-123 15-(p-iodophenyl)-3R, S-methyl pentadecanoic acid (BMIPP), a branched fatty acid analog, has become clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. This perfusion metabolic mismatch, which is also observed by FDG-PET, is identified with stunned or hibernating myocardium with regional dysfunction. Both are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting use as an ischemic memory imaging. These new techniques will provide insights into new pathological states in ischemic heart disease and help to select the optimal treatment for the patients.

Low-dose dobutamine electrocardiograph-gated myocardial SPECT for identifying viable myocardium: comparison with dobutamine stress echocardiography and PET.

UNLABELLED: The identification of severely dysfunctional but viable myocardium is of particular importance for the selection of patients with depressed left ventricular function who will benefit from coronary revascularization. Assessment of inotropic reserve with dobutamine has recently been used for this purpose. This study compared the accuracy of low-dose dobutamine stress gated myocardial SPECT (DS SPECT) with the accuracy of dobutamine stress echocardiography (DSE) and resting perfusion SPECT for the identification of viable myocardium in patients with previous myocardial infarction. METHODS: Resting and low-dose dobutamine (7.5 microg/kg/min) gated (99m)Tc-tetrofosmin SPECT and echocardiography and resting (18)F-FDG PET were prospectively studied in 23 patients with previous myocardial infarction and severely depressed regional function. Twenty-one of them were successfully studied with each technique. The left ventricular wall was divided into 14 segments to assess wall motion using a 5-point scale. PET viability was defined as FDG uptake >/= 50% of the maximum uptake in a region with normal wall motion. For DS SPECT and DSE studies, viable myocardium was defined as hypokinetic areas with > or = 1 point improvement in wall motion. For resting perfusion SPECT, viable myocardium was defined as hypokinetic areas with a relative uptake > or = 50% of the maximum uptake. RESULTS: Of a total of 294 segments, 55 had severe resting dyskinesis. Thirty-four segments were identified as viable on FDG PET, and 21 segments were identified as nonviable. Eleven segments were inadequately visualized with DSE, including 5 segments in the apex. Sensitivities (78% vs. 76%) and specificities (94% vs. 100%) were similar for DSE and DS SPECT, with a concordance of 86% (kappa = 0.72). DS SPECT and perfusion SPECT did not significantly differ with respect to sensitivities (76% vs. 85%, respectively). However, specificity was significantly higher for DS SPECT than for perfusion SPECT (100% vs. 52%, respectively, P < 0.05). CONCLUSION: This study indicated that DS SPECT correlates well with DSE in the assessment of viability. In addition, gated SPECT can evaluate regional wall motion, even in areas inadequately assessed by echocardiography. DS SPECT may also provide additional information for identifying viable myocardium, which is often overestimated by routine perfusion scans.

[18F-FDG injections produced by a solid phase 18F-fluorination (FDG MicroLab): effects of 18F-FDG and the components on endotoxin and sterility tests].

Effects of 18F-FDG and components of the injections on endotoxin tests (Limulus tests) and sterility tests (Blood culture system) were determined with 18F-FDG injections produced by a solid phase 18F-fluorination (FDG MicroLab, GE). 18F-FDG injections with endotoxins shortened the time for gelling (turbidimetry), compared with that of the control (saline). Blood culture systems inoculated with 18F-FDG injections and microorganisms showed positive results within 72 h of incubation for every species of microorganisms used in the present study (Bacillus subtilis, Candida albicans, Clostridium sporogenes, Micrococcus luteus). These results were quite similar to those for the control samples inoculated with saline and the microorganisms. Consequently, 18F-FDG and the components of the injections produced by the present methods may not significantly affect the endotoxin tests and sterility tests.

Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in diagnosis of recurrent or metastatic thyroid carcinoma.

UNLABELLED: There are several reports about the usefulness of (18)F-FDG PET in thyroid cancer. However, few studies have compared FDG PET with (131)I and (201)Tl scintigraphy. The aim of this study was to evaluate the clinical significance of whole-body FDG PET in differentiated thyroid cancer and to compare the results with those obtained from (131)I and (201)Tl scintigraphy. METHODS: Whole-body FDG PET was performed on 32 patients (10 men, 22 women; age range, 30-77 y; mean age, 54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of papillary cancer) after total thyroidectomy. An overall clinical evaluation was performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to allow a comparison with functional imaging results for each patient. Metastatic regions were divided into five areas: neck, lung, mediastinum, bone, and other. Multiple lesions in one area were defined as one lesion. The tumor-to-background ratio (TBR) was measured for the lesions that were positive for both (201)Tl uptake and FDG PET uptake. RESULTS: The number of lesions totaled 47. Forty-one (87%) were detected by all scintigraphic methods. FDG uptake was concordant with (131)I uptake in only 18 lesions (38%). FDG uptake was concordant with (201)Tl uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and positive for (201)Tl uptake, and two lesions were positive for FDG uptake and negative for (201)Tl uptake. A significant correlation was seen between the TBR of (201)Tl and that of FDG (r = 0.69; P<0.05). CONCLUSION: These data indicate that for detecting metastatic lesions, FDG PET and (131)I scintigraphy may provide complementary information, whereas FDG PET may provide results similar to those of (201)Tl scintigraphy. Thus, the combination of (131)I scintigraphy and FDG PET (or (201)Tl scintigraphy) is the method of choice for detecting metastatic thyroid cancer after total thyroidectomy.

Performance assessment of O-18 water purifier.

In the synthesis of 18F-FDG by the nucleophilic substitution method, 18O-H2O is usually used as target water. The target water should be recovered after synthesis and reused, because it is expensive, but recovered water contains impurities such as organic substances, and it must be purified before reuse. For this reason Sumitomo Heavy Industries, Ltd. developed an O-18 water purifier for elimination of organic substances in recovered water. This instrument consists of a UV irradiation unit and low-temperature distillation unit. Our institution had an opportunity to test use this instrument and evaluated its performance. The concentrations of organic substances after UV irradiation was greatly reduced, and recovery efficiency after distillation by the low-temperature distillation unit was very satisfactory at 99.3 +/- 0.5%. Furthermore, the yield of 18F-FDG from 18O-H20 purified with this instrument was sufficient for the clinical use.

Serial changes in cerebral blood flow and flow-metabolism uncoupling in primates with acute thromboembolic stroke.

The authors recently developed a primate thromboembolic stroke model. To characterize the primate model, the authors determined serial changes in cerebral blood flow (CBF) and the relation between CBF and cerebral metabolic rate of glucose (CMRglc) using high-resolution positron emission tomography. Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot into the left internal carotid artery. Cerebral blood flow was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 24 hours after embolization. Lesion size and location 24 hours after embolization was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The results are summarized as follows: (1) 1 hour after embolization, CBF in the temporal cortex and the basal ganglia decreased to < 40% of the contralateral values. In these regions, regarded as an ischemic core, CBF decreased further with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated by being unstained with TTC were consistently observed in these regions. (2) In the parietal cortex and several regions surrounding the ischemic core, CBF was > 40% of the contralateral values 1 hour after embolization and recovered gradually with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased compared with that in the contralateral regions, indicating an uncoupling of CBF and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron emission tomography investigations using this model will provide better understanding of the pathophysiology of thromboembolic stroke in humans.

Experimental thromboembolic stroke in cynomolgus monkey.

To develop an experimental model of thromboembolic stroke without intracranial surgery, an autologous blood clot was delivered to the middle cerebral artery (MCA) via the internal carotid artery in cynomolgus monkeys. Male cynomolgus monkeys, in which a chronic catheter had been earlier implanted in the left internal carotid artery, were used. The clot was flushed into the internal carotid artery under sevofluorane anesthesia. A neurologic deficit score was assigned after MCA embolization. After 24 h, cerebral infarct size and location were determined by the TTC staining method. Cerebral blood flow (CBF) was measured prior to and after MCA embolization, using positron emission tomography (PET). After embolization, long-lasting and profound extensor hypotonia of the contralateral upper and lower limbs, and mild to severe incoordination were observed. Contralateral hemiplegia was observed over the following 24 h. In gross morphologic observation of the brain, the lesions involved mostly the caudate nucleus, putamen, globus pallidus and insular cortex. CBF was maximally reduced in the left MCA territory, but not in the right MCA territory. This model is relevant to thromboembolic stroke in human in neurologic dysfunction and histopathologic brain damage.

Retinoic acid stimulates erythropoietin gene transcription in embryonal carcinoma cells through the direct repeat of a steroid/thyroid hormone receptor response element half-site in the hypoxia-response enhancer.

We have previously reported that expression of the erythropoietin (Epo) gene in mouse embryonal cells was not induced by hypoxia, although hypoxia induced other hypoxia-inducible genes. This study identifies retinoic acid (RA) as an inducer for Epo production in the embryonal carcinoma cell lines P19 and F9. RA induced Epo production through the transcriptional activation of the Epo gene in an oxygen-independent manner. With the use of reporter assays in P19 cells, it is shown that a direct repeat of the nuclear hormone receptor-binding motif separated by a 2-bp spacer (DR-2) in the hypoxia-response enhancer was responsible for the transcriptional activation by RA. Electrophoretic mobility shift assays show that nuclear extracts from P19 cells contained RA receptor complexes that bound to DR-2. In human hepatoma Hep3B cells, an orphan receptor, hepatocyte nuclear factor-4, strongly augmented hypoxic induction of the Epo gene in cooperation with hypoxia-inducible factor-1 (HIF-1) by binding to DR-2, whereas in P19 cells, the interaction of RA receptors with DR-2 was sufficient for RA-induced transcriptional activation of the Epo gene without the requirement of the HIF-1 site. These results suggest that DR-2 regulates expression of the Epo gene by acting as the binding site for different transcription factors in different types of cells.

The role of fatty acids in cardiac imaging.

Nuclear medicine has progressed in conjunction with the recent growth of molecular medicine. Myocardial energy metabolism has long been investigated in experimental models with the use of Langendorff's method or coronary sinus blood sampling. However, the introduction of a variety of radiopharmaceutical agents has now made possible easy visualization of myocardial energy metabolism in vivo with nuclear medicine techniques.

[1-11C]Octanoate as a PET tracer for studying ischemic stroke: evaluation in a canine model of thromboembolic stroke with positron emission tomography.

Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. Consequently, [1-11C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1-11C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1-11C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2,3,5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1-11C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1-11C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1-11C]octanoate relative to CBF takes place in these regions. In conclusion, [1-11C]octanoate accumulated in ischemic but vital regions, indicating that [1-11C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke.