BACKGROUNDMiddle mediastinal masses comprise a wide variety of tumors but may also reflect lymphadenopathy, and thus remain an interesting diagnostic challenge. We performed positron emission tomography (PET) of mediastinal masses in order to evaluate the ability of PET to predict the malignancy of these tumors. We compared histologic findings, videomediastinoscopy, computed tomography (CT), and PET-CT in patients with mediastinal disease.

METHODSThirty-two patients were evaluated with CT, PET-CT and videomediastionoscopy, and all studies were performed within four weeks in each patient. (11)C-choline as a PET tracer was used to visualize masses. PET data were evaluated using the standardized uptake value (SUV) and were compared with pathologic data.

RESULTSThere were 13 men and 19 women aged from 21 to 74 (mean 45.2) years. Among the patients with mediastinal diseases, sarcoidosis was diagnosed in 12 patients, tuberculosis in 5 patients, lymphoma in 5 patients, and noncaseating granulomata without classical "sarcoid" finding in 3 patients. N2 or N3 nodal metastasis was revealed in 6 of 7 patients who had non-small cell lung cancer or suspected lung cancer, and one was negative (the pathological diagnosis was reactive hyperplasia). The accuracies for correctly diagnosing mediastinal masses for CT, PET-CT and videomediastinoscopy were 38% (12/32), 63% (20/32), and 91% (29/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 11.130, P < 0.001). The SUVs were similar among these diseases. On the other hand, if the diagnostic classification was benign vs malignancy, the accuracies for CT, PET-CT and videomediastinoscopy were 53% (17/32), 75% (24/32), 100% (32/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 22.042, P < 0.001). The SUV of malignant lesions (6.9, 3.2 - 9.8; n = 11) appeared to be higher than that of benign lesions (4.9, 2.9 - 8.3; n = 21), however, this difference was not statistically significant (P = 0.054).

CONCLUSIONSTo diagnose lesions located in the middle mediastinum, videomediastinoscopy possesses the highest diagnostic accuracy, and therefore remains the gold standard. PET-CT is valuable for differential diagnosis of benign vs malignant lesions, CT alone or PET alone (SUV) may provide misdiagnosis in a substantial proportion of patients with mediastinal masses.

Adult ; Aged ; Carbon Radioisotopes ; Female ; Humans ; Male ; Mediastinal Diseases ; diagnosis ; Mediastinoscopy ; methods ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; Video Recording

This study was to determine which of two routes of administration of 5-fluorouracil (5-FU) is more effective, by measuring the radioactvity in the body tissues of gastric cancer patients after the administration of 5-FU-l4C via the systemic intravenous and the regional intra-arterial routes. After the drug was administered intravenously in one group of patients, and intra-arterially in another; samples of portal venous blood, the liver, the lymph nodes, and the normal and the cancerous tissues of the stomach were obtained. The radioactivities of the samples were measured, and it was found that those of the regional lymph nodes, the liver, and the normal and the cancerous tissues of the stomach were much higher in the latter group. The regional intra-arterial routes is the more effective way to administer 5-FU in patients with stomach cancer.
Carbon Radioisotopes/diagnostic use ; Comparative Study ; Fluorouracil/administration & dosage ; Fluorouracil/metabolism* ; Human ; Injections, Intra-Arterial ; Injections, Intravenous ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/metabolism

OBJECTIVETo establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product.

METHODS(11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied.

RESULTS(11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice.

CONCLUSIONThe (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.

Animals ; Carbon Radioisotopes ; Contrast Media ; chemical synthesis ; Isoquinolines ; adverse effects ; chemical synthesis ; Mice ; Positron-Emission Tomography ; Radioligand Assay ; Radiopharmaceuticals ; adverse effects ; chemical synthesis ; Receptors, GABA-A ; metabolism

BACKGROUND(11)C-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035) has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor (EGFR). However it is still unclear whether (11)C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between (11)C-PD153035 accumulation and EGFR expression levels.

METHODSSynthesis of (11)C-PD153035 was performed in the Tracerlab FXc system. Accumulation of (11)C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. (11)C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography (PET/CT). Tumor/normal muscle tissue (T/NT) analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The (11)C-PD153035 accumulation in different tumors was determined by a gamma counter.

RESULTSClose correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo (r(2) = 0.72, P < 0.001; r(2) = 0.63, P = 0.003). When the static T/NT analysis method was applied to analyze the PET data, the observed correlation was again excellent (r(2) = 0.70, P = 0.001).

CONCLUSIONSThe uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.

Animals ; Carbon Radioisotopes ; Cell Line, Tumor ; Female ; Humans ; Ligands ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Positron-Emission Tomography ; Quinazolines ; metabolism ; Receptor, Epidermal Growth Factor ; analysis ; metabolism

BACKGROUND: This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats. METHODS: Cirrhotic rats(n=6) were induced by intramuscular injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C0, AUC, t(1/2(beta)), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain. RESULTS: In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p < 0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p < 0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline. CONCLUSION: H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process.
Animals ; Carbon Tetrachloride Poisoning/*complications ; Chromatography, High Pressure Liquid ; English Abstract ; Liver Cirrhosis, Experimental/*metabolism/physiopathology ; Portal System/physiopathology ; Propranolol/*pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Thallium Radioisotopes/diagnostic use

Glycerophosphrylocholine (GPC) is a renal medullary compatible organic osmolyte that is derived from choline via phosphatidylcholine, which is catalyzed in part by phospholipase A2 (PLA2) and its degradation by GPC: choline phosphodiesterase (GPC: choline PDE). We found that caffeine elevated intracellular free calcium ([Ca2+]i) and GPC level in cultured MDCK cells, canine kidney epithelial cells, and propose a possible biochemical mechanism. When MDCK cells were incubated for 3 h with 1 to 10 mM caffeine, cellular GPC was elevated in a dose-dependent manner, and this occurred independently of the extracellular osmolality. Caffeine stimulated the rate of [14C]choline incorporation into [14C]GPC and PLA2 activity. Whereas, GPC: choline PDE activity was accompanied by less of increase. These enzyme changes demonstrate the increased net synthesis of MDCK GPC. In order to identify what triggers the PLA2 activation, [Ca2+]i was measured by using a fluorescence dye, Fura-2. Caffeine (10 mM) resulted in a typical transient increase in MDCK [Ca2+]i concentration, and this increase was greatly inhibited by pretreatment of MDCK cells with 10 mM ryanodine for 5 min. Ryanodine (10 mM) also inhibited the caffeine-induced stimulation of PLA2 activity. These findings provide the first evidence that caffeine in MDCK cells causes a ryanodine-inhibitable increase of [Ca2+]i and PLA2 activity, resulting in cellular GPC accumulation.
Animal ; Caffeine/pharmacology* ; Calcium/metabolism* ; Carbon Radioisotopes ; Cell Line ; Choline/metabolism ; Dogs ; Glycerylphosphorylcholine/metabolism* ; Kidney/cytology ; Phospholipases A/metabolism* ; Phospholipases A/drug effects ; Phospholipases A/antagonists & inhibitors ; Phosphoric Diester Hydrolases/metabolism ; Phosphoric Diester Hydrolases/drug effects ; Ryanodine/pharmacology* ; Ryanodine/metabolism

OBJECTIVEThe objective of this study was to compare the biodistribution and PET imaging of (11)C-PDT and (18)F-FDG in a mouse model of lung adenocarcinoma, and to evaluate the value of (11)C-PDT as a new tracer for PET imaging of lung cancer.

METHODSTwenty four lung adenocarcinoma-bearing mice were randomly divided into two groups, 12 each. The mice received (11)C-PDT or (18)F-FDG injection i.v. respectively. The biodistribution of (11)C-PDT or (18)F-FDG in the mice was measured with a well-gamma detector at 60 min after injection. The PET imagings of mice were performed using either of the two tracers.

RESULTSConsiderable uptake of the both radioactive tracers in the tumors was observed. The tumor uptake of (11)C-PDT [(0.65 +/- 0.20)%ID/g] was significantly lower than that of (18)F-FDG [(7.44 +/- 1.56)%ID/g, P < 0.01]. In the (11)C-PDT group, the highest uptake was observed in the liver, kidney and blood in a successively declining order, while the highest uptake of (18)F-FDG was seen in a order of heart, tumor and kidneys. The tumor/muscle ratio of (11)C-PDT uptake was relatively high (2.02 +/- 0.56), but still lower than that of (18)F-FDG (2.95 +/- 0.49, P < 0.01). All values of other tumor/organ ratios (T/NT) of (11)C-PDT uptake were < 2. High radioactive uptake was showed in the tumor and abdominal organs on PET images in the tumor-bearing mice injected with (11)C-PDT, and (18)F-FDG uptake was showed in the heart, tumor and abdominal organs. The tumor PET images with (11)C-PDT and (18)F-FDG were all clear.

CONCLUSIONThe uptake of (11)C-PDT in lung cancer is higher than that in muscle tissues, and pulmonary cancers can be detected by PET imaging. (11)C-PDT may be a promising PET tracer for lung cancers.

Adenocarcinoma ; diagnostic imaging ; metabolism ; pathology ; Animals ; Carbon Radioisotopes ; pharmacokinetics ; Cell Line, Tumor ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Kidney ; diagnostic imaging ; metabolism ; Liver ; diagnostic imaging ; metabolism ; Lung Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Mice ; Myocardium ; metabolism ; Podophyllotoxin ; pharmacokinetics ; Positron-Emission Tomography ; Tissue Distribution

OBJECTIVETo evaluate the potential benefit of carbon ion radiotherapy (C-ion RT) through comparison with photon intensity-modulated radiotherapy (IMRT) in dose distribution for prostatic adenocarcinoma.

METHODSIn randomly selected 5 patients, treatment planning of C-ion RT (4 coplanar beams) and IMRT (7 coplanar fields) were worked out by computer working station. In order to make a meaningful comparison, it was defined that the 95% isodose surface had to cover 100% of the PTV in each plan; all dose was given as normalized dose with the definition of the minimum dose of the PTV being equal to 95% of prescribed dose. Dose-volume histograms (DVHs) of the tumor and organ-at-risks (OARs) were calculated. Volume irradiated more than or equal to some specified doses, conformity index ( CI) , and inhomogeneity coefficient (IC) of each treatment plan was compared, respectively.

RESULTSWith C-ion RT, the mean irradiated volumes (in %) of the rectum were significantly smaller than that with IMRT except for 95% dose level, and C-ion RT could provide complete protection to the posterior rectal wall. In addition, C-ion RT could also remarkably reduce the dose to the bladder, femoral heads and non-target normal tissues at each dose level. Dose conformation and homogeneity in the target volume of C-ion RT were better than that in IMRT (mean CI50%, 3.36 vs. 5.04, mean CI95%, 1.20 vs. 1.46, mean IC, 0.03 vs. 0.12).

CONCLUSIONCompared with IMRT, C-ion RT can obtain better dose distribution, and may reduce tumor recurrence and radiation-induced complications in prostatic adenocarcinoma.

Adenocarcinoma ; pathology ; radiotherapy ; Aged ; Carbon Radioisotopes ; therapeutic use ; Femur Head ; radiation effects ; Humans ; Male ; Prostatic Neoplasms ; pathology ; radiotherapy ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; methods ; Rectum ; radiation effects ; Urinary Bladder ; radiation effects

OBJECTIVETo assess the value of carbon-11 choline (CH) positron emission tomography (PET) in patients with pulmonary nodules.

METHODSFrom September 2002 to December 2004, 39 patients with pulmonary nodules were imaged with CH-PET. CH-PET data was analyzed by visual method and semiquantitative method. When pulmonary nodules with abnormal CH uptake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) were measured using semiquantitative method. Diagnoses were confirmed by surgery or biopsy and follow-up survey.

RESULTSTwenty-four cancerous and 3 inflammatory nodules and 1 bronchogenic cyst were detected by CH-PET and were diagnosed malignant with visual method. Three bronchial alveolar carcinoma, 2 metastatic tumor from kidney and colon, 3 fibrous nodules, 1 cryptococcosis, 1 hamartoma and 1 sclerosing hemangioma showed nothing abnormal in PET scans. For identification of pulmonary nodules with CH-PET, the sensitivity was 89% (24/29), the specificity was 60% (6/10), and the accuracy was 77% (30/39). There were differences in SUV between 8 squamous cell carcinomas and 9 adenocarcinomas (Z = -2.937, -2.887, P < 0.01). In diagnosing 70 resected enlarged lymph nodes beyond 1 cm in 17 lung cancer patients, CH-PET had the sensitivity of 86% (25/29), the specificity of 90% (37/41), and the accuracy of 89% (62/70). CH-PET confirmed 7 distant metastases in 25 lung cancer patients. In 5 cases suspected brain metastases CH-PET identified 2 cases positive correctly.

CONCLUSIONSCH-PET can confirm malignant pulmonary nodules, but still there were false positive and false negative cases. CH-PET can evaluate N stage effectively in patients with lung cancer. CH-PET can depict brain metastases accurately.

Adult ; Aged ; Aged, 80 and over ; Carbon Radioisotopes ; Choline ; Female ; Humans ; Lung ; diagnostic imaging ; pathology ; Lung Diseases ; diagnosis ; Lung Neoplasms ; diagnosis ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Retrospective Studies ; Sensitivity and Specificity

Animals ; Carbon Radioisotopes ; Diabetes Mellitus, Experimental ; genetics ; metabolism ; Diabetes Mellitus, Type 1 ; genetics ; metabolism ; Gene Expression Regulation ; Glucose ; administration & dosage ; metabolism ; Lipid Metabolism ; Liver ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Transcriptome