Rapid rise in FDG uptake in an irradiated human tumour xenograft

In order to investigate early changes in the glucose metabolism of irradiated tumours, tumour uptake of 2-[¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸FDG) was studied in human tumour xenografts. Three human tumour lines [ependymoblastoma (NNE), small cell lung cancer (GLS), and glioblastoma (KYG)] showing different radiosensitivities and incidences of radiation-induced apoptosis were subcutaneously transplanted into nude mice, and were irradiated at a single dose of 10 Gy. Then 0.5 mCi of¹⁸FDG was intravenously administered 1 h before sacrifice. The animals were sacrificed at 2, 4 and 6 h following irradiation, and¹⁸FDG accumulation in the tumours was examined. Before irradiation, GLS and KYG tumours showed significantly higher rates of¹⁸FDG accumulation compared with NNE tumours (P <0.004 andP <0.001, respectively). NNE (the most radiosensitive tumour with the highest incidence of radiation-induced apoptosis), however, displayed a 2.3-fold higher rate of¹⁸FDG accumulation at 2 h following irradiation compared with a non-irradiated group (P <0.01), and thereafter showed a plateau up to 6 h. The accumulation did not increase significantly in the other tumours with lower radiosensitivity and much less radiation-induced apoptosis. The rapidity of the increase in¹⁸FDG accumulation in the most radiosensitive tumour line, occurring as early as 2 h following irradiation, suggests that the increase was independent of recovery phenomena following radiation damage.     

Regional 2-[18F]fluoro-2-deoxy-d-glucose uptake varies in normal lung

2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a promising imaging procedure for detecting primary and metastatic cancer in the lungs. We have, however, failed to detect some small tumors in the lower lobes of the lungs. This study aimed to determine whether increase¹⁸F background activity in the dependent lower lungs is present, which could make lesion detection more difficult. We measured the standardized uptake values (SUVs) for FDG of normal lung remote from the nodular lesion in 16 patients with newly diagnosed untreated lung lesions stronlgy suspected to represent non-small cell lung cancers. In addition, 15 patients with known or suspected primary breast cancers without pulmonary lesions were included as control subjects. After PET transmission images of the thorax were obtained, approximately 370 MBq of FDG was injected intravenously and imaging was immediately begun. Patients were supine throughout the study. SUVs were determined with images obtained 50–70 min after FDG injection. Regions of interest (ROls) of 6×6 pixels were positioned over normal lung in anterior, mid, and posterior portions of upper, middle, and lower lung fields. Thus, as many as 18 ROls were positioned in each patient. The SUVs of the posterior portion were significantly higher than those of the anterior and mid portions in the population of 31 cases (P <0.001). Also, the mean SUV of the lower lung field was significantly higher than the SUVs of the upper and middle lung fields in this population (P <0.01). This pattern was seen among the two groups of 16 patients suspected of having lung cancer and 15 control subjects. Background¹⁸F activity was highest in posterior and lower lung in these patients. The maximum value of mean SUV observed in normal posterior lower lung was 0.804±0.230 (41% greater than the mean SUV in the anterior upper lung), which is in the range of the apparent SUV for a 5-mm lung lesion, with higher SUV, due to recovery coefficient issues. Thus this phenomenon could contribute to occasional false-negative lesions in those areas. Increased blood flow and FDG delivery and also scatter from heart and liver may contribute to the increased lower lung background activity. Regional differences in normal lung FDG uptake are significant and should be considered when interpreting pulmonary PET studies in patients with suspected primary or metastatic lung cancer.     

The usefulness of FDG positron emission tomography for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer: a comparative study with X-ray computed tomography

We evaluated the usefulness of fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) in the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer and then compared the findings with the results of X-ray CT by region based on the histological diagnoses. We examined 29 patients with non-small cell lung cancer. One hundred and thirty-two mediastinal lymph nodes were surgically removed and the histological diagnoses were confirmed. FDG PET images, including 146 mediastinal regions, were visually analysed and the mediastinal lymph nodes were scored as positive when the FDG uptake was higher than that in the other mediastinal structures. On the X-ray CT scans, any mediastinal lymph nodes with a diameter of 10 mm or larger were scored as positive. All three examinations were successfully performed on 71 regions. For FDG PET, we found a sensitivity of 76%, a specificity of 98% and an accuracy of 93%. On the other hand, for X-ray CT a sensitivity of 65%, a specificity of 87% and an accuracy of 82% were observed. A significant difference was observed in respect of both specificity and accuracy (P<0.05). Based on the above findings, FDG PET is suggested to be superior to X-ray CT when used for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer.     

Prospective evaluation of fluorine-18 fluorodeoxyclucose positron emission tomography in breast cancer for staging of the axilla related to surgery and immunocytochemistry

The noninvasive staging of axillary lymph nodes for metastases is investigated in patients with breast cancer prior to surgery by positron emission tomography (PET) with fluorine- l8-fluoro-2-deoxy-d-glucose (¹⁸F-FDG). In 124 patients with newly diagnosed breast cancer, whole-body PET was performed to determine the average differential uptake ratio (DUR) of¹⁸F-FDG in the axillary lymph nodes. Results were correlated with the number of the dissected lymph nodes, size of the primary tumor, tumor type, tumor grade, estrogen and progesterone receptors, DNA ploidy, and the proportion of cells in the synthetic phase of the cell cycle (S-phase). In this prospective study of 124 patients with breast carcinoma, PET correctly categorized all 44 tumor-positive axillary lymph nodes, a sensitivity of 100%. Sixty tumor-negative axillary lymph nodes were negative by PET and 20 tumor-negative axillary lymph nodes were positive by PET. No false-negative PET findings were encountered. A weak correlation was found between DUR and tumor size as well as between DUR and the S-phase of the tumor. In patients with breast carcinoma,¹⁸F-FDG PET can be of value in evaluating axillary lymph nodes for metastatic involvement prior to surgery. It is of particular importance that no false-negative PET findings were encountered, and axillary lymph node dissection might not be necessary in patients without axillary uptake by PET. The DUR of the positive axillary lymph nodes seems to bear a relationship with some of the purported prognostic parameters of the primary tumor.     

FDG PET imaging of paragangliomas of the neck: comparison with MIBG SPET

Two patients with cervical paragangliomas underwent positron emission tomography (PET) with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG). There was marked tumor uptake and retention of FDG. Adjacent salivary gland accumulation of FDG was minimal, though quite prominent withmeta-iodobenzylguanidine. FDG PET offers another potentially useful approach to functional imaging of these uncommon tumors, independent of the presence of specific amine uptake mechanisms or cell surface receptors required by other scintigraphic techniques.     

Distant metastases and synchronous second primary tumors in patients with newly diagnosed oropharyngeal and hypopharyngeal carcinomas: evaluation of <Superscript>18</Superscript>F-FDG PET and extended-field multi-detector row CT

Introduction  Patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) have a high risk of having distant metastases or second primary tumors. We prospectively evaluate the clinical usefulness of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG PET), extended-field multi-detector computed tomography (MDCT), and their side-by-side visual correlation for the detection of distant malignancies in these two tumors at presentation. Materials and methods  A total of 160 patients with SCC of the oropharynx (n = 74) or hypopharynx (n = 86) underwent ¹⁸F-FDG PET and extended-field MDCT to detect distant metastases or second primary tumors. Suspected lesions were investigated by means of biopsy, clinical, or imaging follow-up. Results  Twenty-six (16.3%) of our 160 patients were found to have distant malignancy. Diagnostic yields of ¹⁸F-FDG PET and MDCT were 12.5% and 8.1%, respectively. The sensitivity of ¹⁸F-FDG PET for detection of distant malignancies was 1.5-fold higher than that of MDCT (76.9% vs. 50.0%, P = 0.039), while its specificity was slightly lower (94.0% vs. 97.8%, P = 0.125). Side-by-side visual correlation of MDCT and ¹⁸F-FDG PET improved the sensitivity and specificity up to 80.8% and 98.5%, respectively, leading to alteration of treatment in 13.1% of patients. A significant difference in survival rates between its positive and negative results was observed. Conclusion   ¹⁸F-FDG PET and extended-field MDCT had acceptable diagnostic yields for detection of distant malignancies in untreated oropharyngeal and hypopharyngeal SCC. ¹⁸F-FDG PET was 1.5-fold more sensitive than MDCT, but had more false-positive findings. Their visual correlation improved the diagnostic accuracy, treatment planning, and prognosis prediction.     

The negative impact of fatty liver on maximum standard uptake value of liver on FDG PET

Purpose

The purpose of the study is to evaluate the impact of fatty liver on maximum standard uptake value (SUVmax) of liver on 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET).

Materials and methods

A total of 173 consecutive healthy subjects were retrospectively recruited for analysis. Subjects with acute renal disease, chronic renal disease, or malignancy were excluded. Demographic data were collected from chart records. All subjects performed whole-body FDG PET, sonography of liver, and glutamic pyruvic transaminase (GPT) level. The SUVmax of liver on FDG PET was calculated. The relationship between the severity of fatty liver and SUVmax of liver on FDG PET was analyzed.

Results

There were significant differences in SUVmax of liver on FDG PET in four groups: no fatty liver, mild-degree, moderate-degree, and severe-degree fatty liver on sonography diagnosis (P=.041). After adjusting for possible covariates age, sex, body mass index, and GPT, there was a significantly negative correlation between the severity of fatty liver and SUVmax of liver on FDG PET (β=−.20, P<.001).

Conclusion

Based on the results of this study, the liver cannot be used as a comparator of extrahepatic foci of equivocal increased FDG activity in patients with fatty liver disease.     

Spatial registration of echocardiographic and positron emission tomographic heart studies

A method has been developed to match corresponding heart regions from functional echocardiographic (Echo) and metabolic fluorine-l8-fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography (PET) studies in individual patients. Echo and PET images are spatially correlated by determining homologous anatomical landmarks (the two papillary muscles and the inferior junction of the right ventricle), identifiable in images obtained by both acquisition modalities. Echo-PET image registration is first performed in the plane identified by the three landmarks, using a rigid rotate-translate scale model. The registration parameters are then used to transform the whole PET volume. This allows a consistent Echo-PET regional analysis, according to a segmental subdivision of the heart. The technique was tested on patients. The overlay of Echo and PET registered images proved the reliability of realignment of the three markers and a good spatial correlation of myocardial walls. This approach to image registration could be applied to other acquisition modalities (such as magnetic resonance imaging and single-photon emission tomography), provided that the three anatomical landmarks are visualized.     

FDG-PET imaging in HIV-infected subjects: relation with therapy and immunovirological variables

Purpose

To characterise tissue sites of immune activation and HIV replication we performed FDG-PET in ART-treated and ART-naive HIV-infected individuals. Specific aims were to establish whether HIV-infected patients can be differentiated on the basis of the detection of specific locations of viral replication, even in the presence of an apparently optimal immunovirological response to ART, and whether these FDG-PET findings can be related to immunovirological variables and AIDS history status.

Patients and methods

Patients were divided into five groups as follows: subgroup A1 (full responders, n?=?8): current ART treatment, CD4+ T lymphocytes >500/mL, viral load <50 copies/mL; subgroup A2 (full responders, n?=?5): same criteria as A-1, but with a previous history of AIDS; subgroup A3 (immunological non responders, n?=?5): current ART treatment, viral load <50 copies/mL, low CD4+ T lymphocytes (<200/mL); group B (virological non responders, n?=?2): current ART treatment, CD4+ T lymphocytes around 500/mL, viral load >50,000 copies/mL; group C (ART-naïve, n?=?5): no current or previous ART treatment, increased viral load.

Results

PET images revealed different patterns of FDG uptake. All ART-treated patients with either suppressed (<50 copies/mL; Group A) or high viremia (group B) showed a normal pattern of FDG uptake. On the contrary, the ART-naïve subjects with high viraemia (group C) displayed multiple foci of increased glucose metabolism in the lymph nodes. In the ART-naïve subjects, FDG uptake, apparently related to viraemia level, was observed in the upper torso mainly in the axillary nodes bilaterally in patients with viraemia below 100,000 copies/mL; in those with viraemia higher than 100,000 copies/mL, FDG uptake was also observed in the inguinal lymph nodes.

Conclusions

The emergence, in our study, of a correlation between the percentage of CD8+/CD38+/RO+ T cells (well established markers of progression to AIDS independently of CD4+ T lymphocytes) and positive FDG-PET in ART-naive patients is a novel finding that seems to confer prognostic value on FDG uptake. FDG uptake is strongly associated with response to ART independently of a previous AIDS diagnosis. Notably, no differences were observed between ART-treated subjects classed as immunological responders and those classed as non responders. Data herewith indicate that FDG uptake and immunological variables are unrelated when ART is being administered. This is evidence of the complementarity of immunological and FDG measures. FDG uptake is a sensitive marker of disease state and its relation with CD8+/CD38+/CD45RO+ T cells indicates that it can be considered a marker of disease status. The lack of a correlation between FDG uptake and immunological variables in patients under ART warrants further investigation.

     

Experimental studies on myocardial glucose metabolism of rats with 18F-2-fluoro-2-deoxy-d-glucose

The myocardial uptake of ¹⁸F-FDG was investigated under various conditions, and compared with brain and tumor uptake as a function of blood glucose level. The uptake by the heart of normal feeding rats was rapid and remained essentially unchanged up to 2 h after ¹⁸F-FDG injection, approximately 3%–4% dose/g tissue. On the other hand, the myocardial uptake of fasted rats was significantly lower than that of control rats throughout the course of the study, and it was about 0.3%–0.4% dose/g tissue. Myocardial uptake of ¹⁸F-FDG was relatively constant at glucose levels under about 120 mg/100 ml and increased steeply at higher blood glucose levels. In contrast, brain uptake decreased linearly with increasing levels of blood glucose, revealing a strong negative correlation between brain uptake of ¹⁸F-FDG and blood glucose levels. The tumor uptake pattern remained relatively unchanged, irrespective of blood glucose levels. It was revealed that the glucose demands of brain, heart, and tumor were entirely different. After a glucose load, the myocardial uptake of fasted rats increased only slightly from 0.4% to 0.6% dose/g tissue, in spite of transitional hyperglycemia. In contrast, insulin caused myocardial uptake to increase extraordinarily, although it caused a decrease in blood glucose levels.     

Crossed cerebellar diaschisis: a positron emission tomography study withl-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-d-glucose

OBJECTIVE: Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl-11C]methionine (MET) uptake is affected in CCD. METHODS: In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. RESULTS: Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017 +/- 0.023 and 0.014 +/- 0.039, respectively). CONCLUSIONS: Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity.     

Diagnosis of maxillofacial tumor withl-3-[18F]-fluoro-α-methyltyrosine (FMT) PET: a comparative study with FDG-PET

OBJECTIVES: To compare L-3-[18F]-fluoro-a-methyltyrosine (FMT)-positron emission tomography (PET) and 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET in the differential diagnosis of maxillofacial tumors. METHODS: This study included 36 patients (16 males, 20 females; 31-90 years old) with untreated malignant tumors (34 squamous cell carcinoma, one mucoepidermoid carcinoma, one rhabdomyosarcoma) and seven patients (five males, two females; 32-81 years old) with benign lesions. In all patients, both FMT-PET and FDG-PET were performed within two weeks before biopsy or treatment of the lesions. To evaluate the diagnostic usefulness of FMT-PET and FDG-PET, visual interpretation and semiquantitative analysis were performed. PET images were rated according to the contrast of tumor uptake as compared with background, and were statistically analyzed. As a semiquantitative analysis, standardized uptake values (SUV) of the primary tumors were measured, and the SUV data were analyzed using receiver operating characteristic (ROC) curves. Results: The mean SUV of the malignant lesions were significantly higher than those of the benign lesions in both FMT-PET (2.62 +/- 1.58 vs. 1.20 +/- 0.30, p < 0.01) and FDG-PET (9.17 +/- 5.06 vs. 3.14 +/- 1.34, p < 0.01). A positive correlation (r = 0.567, p < 0.0001, n = 46) was noted between FMT and FDG. ROC analysis revealed that there was no statistically significant difference in SUVs between FMT and FDG for differentiating malignant tumors. In 27 of 36 patients, FMT-PET had better contrast of malignant tumor visualization to the surrounding normal structures by visual assessment (p < 0.005, binomial proportion test). CONCLUSIONS: Differential diagnosis of FMT-PET based on the uptake in maxillofacial tumors is equivalent to FDG-PET. However, the contrast of FMT uptake between maxillofacial tumors and the surrounding normal structures is higher than that of FDG, indicating the possibility of accurate diagnosis of maxillofacial tumors by FMT-PET.     

Preliminary results for positron emission mammography: real-time functional breast imaging in a conventional mammography gantry

In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy.     

Positron detection for the intraoperative localisation of cancer deposits

Purpose The study investigated the feasibility of a positron-sensitive hand-held detector system for the intraoperative localisation of tumour deposits resulting from intravenous [¹⁸F]FDG administration. Methods A total of 17 patients (12 receiving preoperative [¹⁸F]FDG PET imaging) with various histologically proven malignancies were included. Radioactivity from tumours and surrounding normal tissue was measured on average 3 h after administration of 36–110 MBq [¹⁸F]FDG and the tumour-to-background (T/B) ratio was calculated. In addition, phantom studies were performed to evaluate the spatial resolution and sensitivity of the probe. Results All known targeted tumour sites were identified by the positron probe. T/B ratios were generally high, with a mean T/B ratio of 6.6, allowing easy identification of most tumour sites. In one case of a hepatic metastasis, the T/B ratio of 1.34 was below expectations, since the preoperative [¹⁸F]FDG PET scan was positive. The probe was instrumental in the localisation of three additional tumour lesions (two lymph nodes, one anastomotic ring) that were not immediately apparent at surgery. Phantom studies revealed that [¹⁸F]FDG-containing gel (simulating tumour tissue), having 10 times more [¹⁸F]FDG than surrounding “normal” background gel, was clearly detectable in quantities as low as 15 mg. As measured in two cases, the absorbed radiation doses ranged from 2.5 to 8.6 μSv/h for the surgical team to 0.8 μSv/h for the aesthetician. Conclusion [¹⁸F]FDG-accumulating tumour tissues can be localised with positron probes intraoperatively with a low radiation burden to the patient and medical personnel. The methodology holds promise for further clinical testing.     

Comparison of three different methods for radiolabelling human activated T lymphocytes

One approach in the treatment of ovarian cancer MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO),indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of¹¹¹In-oxine and¹⁸F-FDG using 2.5×10⁸ lymphocytes (68% and 64%, respectively) were more than twice that of^99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of¹¹¹In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the^99mTc label in the same period and 45% of¹⁸F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both¹¹¹In-oxine and¹⁸F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8–9 days. Radiolabelling with the more stable¹¹¹In-oxine reagent using a higher number of lymphocytes (1.4x109) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that¹¹¹In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.     

Metabolic–dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson’s disease

Purpose The unilateral 6-hydroxydopamine (6-OHDA) lesion rat model is a well-known acute model for Parkinson’s disease (PD). Its validity has been supported by invasive histology, behavioral studies and electrophysiology. Here, we have characterized this model in vivo by multitracer imaging [glucose metabolism and dopamine transporter (DAT)] in relation to behavioral and histological parameters. Methods Eighteen female adult Wistar rats (eight 6-OHDA-lesioned, ten controls) were investigated using multitracer [¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) and [¹⁸F]-FECT {2′-[¹⁸F]-fluoroethyl-(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)-8-azabicyclo(3.2.1)-octane-2-carboxylate} small animal positron emission tomography (PET). Relative glucose metabolism and parametric DAT binding images were anatomically standardized to Paxinos space and analyzed on a voxel-basis using SPM2, supplemented by a template-based predefined volumes-of-interest approach. Behavior was characterized by the limb-use asymmetry test; dopaminergic innervation was validated by in vitro tyrosine hydroxylase staining. Results In the 6-OHDA model, significant glucose hypometabolism is present in the ipsilateral sensory-motor cortex (−6.3%; p = 4 × 10⁻⁶). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p < 5 × 10⁻⁹), as confirmed by the behavioral and histological outcomes. Correlation analysis revealed a positive relationship between the degree of DAT impairment and the change in glucose metabolism in the ipsilateral hippocampus (p = 3 × 10⁻⁵), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment (p < 3 × 10⁻⁴). Conclusions In vivo cerebral mapping of 6-OHDA-lesioned rats using [¹⁸F]-FDG and [¹⁸F]-FECT small animal PET shows molecular–functional correspondence to the cortico-subcortical network impairments observed in PD patients. This provides a further molecular validation supporting the validity of the 6-OHDA lesion model to mimic multiple aspects of human PD.     

Increased accuracy of the carbon-14d-xylose breath test in detecting small-intestinal bacterial overgrowth by correction with the gastric emptying rate

To date, there is no general agreement as to which test is to be preferred for the diagnosis of small-intestinal bacterial overgrowth. The 1-g carbon-14d-xylose breath test has been proposed as a very sensitive and specific test for the diagnosis of bacterial overgrowth. However, in patients with severe gastrointestinal motor dysfunction, the lack of consistent delivery of¹⁴C-d-xylose to the region of bacterial contamination may result in a negative result. The aim of this study was to determine whether the accuracy of¹⁴C-d-xylose breath test for detecting bacterial overgrowth can be increased by correction with the gastric emptying rate of¹⁴C-d-xylose. Ten culture-positive patients and ten culture-negative controls were included in the study. Small-intestinal aspirates for bacteriological culture were obtained endoscopically. A liquid-phase gastric emptying study was performed simultaneously to assess the amount of¹⁴C-d-xylose that entered the small intestine. The results of the percentage of expired¹⁴CO₂ at 30 min were corrected with the amount of¹⁴C-d-xylose that entered the small intestine. There were six patients in the culture-positive group with a¹⁴CO₂ concentration above the normal limit. Three out of four patients with initially negative results using the uncorrected method proved to be positive after correction. All these three patients had prolonged gastric emptying of¹⁴C-d-xylose. When compared with cultures of small-intestine aspirates, the sensitivity and specificity of the uncorrected¹⁴C-d-xylose breath test were 60% and 90%, respectively. In contrast, the sensitivity and specificity of the corrected¹⁴C-d-xylose breath test improved to 90% and 100%, respectively. In conclusion, using the gastric emptying rate of¹⁴C-d-xylose as a correcting factor, we found a higher sensitivity and specificity for the¹⁴C-d-xylose breath test in the detection of small-intestinal bacterial overgrowth than were achieved with the conventional method.     

High- and moderately high-methionine uptake demonstrated by PET in a patient with a subacute cerebral infarction

In patients with cerebral tumors, high accumulations of L-methyl-11C-methionine (11C-Met) have been reported in some cases of cerebral ischemic disease, but no high accumulations of 11C-Met in areas where only transient arterial occlusions are most likely to occur have been reported. Herein we present a case of a high accumulation of 11C-Met in an area of frontal interhemispheric cerebral infarction and a moderately high accumulation with an unclear margin in a distant frontal convexity area. A craniotomy revealed a subacute stage of cerebral infarction in the interhemispheric lesion, and an ischemic change in the distant convexity area. Sixteen months after onset, CT scans demonstrated an infarction area in the interhemispheric lesion only, and no atrophic changes were observed in the distant convexity area indicating that no serious tissue damage had occurred.     

123/125I-labelled 2-iodo-L-phenylalanine and 2-iodo-D-phenylalanine: comparative uptake in various tumour types and biodistribution in mice

Purpose In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [¹²³I]-2-iodo-L-phenylalanine and [¹²³I]-2-iodo-D-phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models.Methods Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [¹²³I]-2-iodo-L-phenylalanine was performed using the method described by Shotwell et al. Subsequently, [¹²³I]-2-iodo-L-phenylalanine and [¹²³I]-2-iodo-D-phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed.Results In vitro testing demonstrated that [¹²³I]-2-iodo-L-phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D-isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [¹²³I]-2-iodo-L-phenylalanine.Conclusion [¹²³I]-2-iodo-L-phenylalanine and its D-isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [¹²³I]-2-iodo-D-phenylalanine showed better tracer characteristics concerning radiation dose to other organs.     

The added value of [<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">L</Emphasis>-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Purpose Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [¹⁸F]fluoro-L-DOPA in distinguishing focal from diffuse HI. Methods Forty-nine children were studied with [¹⁸F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45–65 min after the injection of 4.2 ± 1.0 MBq/kg of [¹⁸F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI. Results We identified abnormal focal pancreatic uptake of [¹⁸F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance. Conclusion These data demonstrate that PET with [¹⁸F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI.