Precise localization of dysfunctional areas in vertebro-basilar infarction by FDG- and O-15-H2O-PET using standardized image analysis and image registration to 3-D MR

The advantages of standardized multimodal image analysis are demonstrated in a case of symptomatic tremor after basilar thrombosis. Functionally and structurally lesioned areas were mapped in Talairach space using 3-D MRI, cerebral FDG-PET and O-15-H2O-PET. Structural lesions were found in the left midbrain, thalamus, putamen and cerebellar areas. Voxel-based statistics in comparison to a normal data base revealed hypometabolism in the left thalamus, left red nucleus, left cerebellar hemisphere including dentate nucleus and in the left inferior olivary nucleus. The O-15-H2O-PET investigation revealed metabolic uncoupling along the rubroolivocerebellar loop. Given the delicate anatomy of the structures involved, image registration and standardized image analysis techniques are essential for a synoptic multimodality analysis of morphological and functional pathology and should generally be used for cerebral PET investigations.     

Functional imaging of malignant paragangliomas and carcinoid tumours

Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared 123I-MIBG, 111In-[D-Phe1]-DTPA-octreotide and 18F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of 111In-[D-Phe1]-DTPA-octreotide and 123I-MIBG. Whole-body PET scans were performed 45 min after injection of 18F-FDG. 111In-[D-Phe1]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, 18F-FDG PET was positive in 11/15 patients and identified 107 lesions and 123I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. 18F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.     

Shorter examination method for the diagnosis of misery perfusion with count-based oxygen extraction fraction elevation in 15O-Gas PET

(15)O-Gas PET is useful for evaluating hemodynamic status in patients with ischemic cerebrovascular disease. To reduce examination time and exposure to radioactive gas, we assessed a count-based method with shorter continuous (15)O(2) gas inhalation. METHODS: Twenty-five patients (66 +/- 13 [mean +/- SD] y old) with unilateral cerebrovascular stenoocclusive disease were examined by use of measurements of asymmetric oxygen extraction fraction (OEF) elevation. Dynamic PET scans of 1 min per frame were obtained starting 2 min after the beginning of (15)O(2) inhalation at a constant flow rate (740 MBq/min). Each subject also underwent C(15)O and H(2)(15)O PET with the bolus administration method. To evaluate the effects of different scan start times and durations during (15)O(2) inhalation, we extracted and summed individual (15)O(2) PET data from the dynamic (15)O(2) dataset. Count-based OEF (cbOEF) images were calculated from (15)O(2) and H(2)(15)O PET images. The asymmetric indices (AI) of cbOEF (cbOEF-AI) were obtained from regions of interest drawn on territories of the bilateral middle cerebral artery. These AI were compared with the AI of quantitative OEF (qOEF-AI). RESULTS: The slopes of the regression lines and the coefficients of correlation between qOEF-AI and cbOEF-AI were close to 1.00 and greater than 0.79, respectively, regardless of different scan start times and durations. The cbOEF-AI obtained with a longer scan duration were closer to the qOEF-AI than those obtained with a shorter scan duration. Longer scan durations also provided better coefficients of correlation between cbOEF-AI and qOEF-AI regardless of scan start times. The coefficients of correlation between cbOEF-AI and qOEF-AI were greater than 0.90, except for cbOEF-AI obtained from (15)O(2) images at 2-3 min after (15)O(2) inhalation. CONCLUSION: The cbOEF obtained by (15)O(2) imaging from 4 min after (15)O(2) inhalation to 7 min or longer can correctly diagnose misery perfusion. The less invasive count-based PET method used in this study will be able to reduce examination time, exposure time, and stress for patients with ischemic cerebrovascular disease.     

Localisation of motor areas in brain tumour patients: a comparison of preoperative [18F]FDG-PET and intraoperative cortical electrostimulation

Assessment of the exact spatial relation between tumour and adjacent functionally relevant brain areas is a primary tool in the presurgical planning in brain tumour patients. The purpose of this study was to compare a preoperative fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) activation protocol in patients with tumours near the central area with the results of intraoperative direct cortical electrostimulation, and to determine whether non-invasive preoperative PET imaging can provide results equivalent to those achieved with the invasive neurosurgical "gold standard". In this prospective study, we examined 20 patients with various tumours of the central area, performing two PET scans (each 30 min after i.v. injection of 134-341 MBq [18F]FDG) in each patient: (1) a resting baseline scan and (2) an activation scan using a standardised motor task (finger tapping, foot stretching). Following PET/MRI realignment and normalisation to the whole brain counts, parametric images of the activation versus the rest study were calculated and pixels above categorical threshold values were projected to the individual MRI for bimodal assessment of morphology and function (PET/MRI overlay). Intraoperative direct cortical electrostimulation was performed using a Viking IV probe (5 pulses, each of 100 micros) and documented using a dedicated neuro navigation system. Results were compared with the preoperative PET findings. PET revealed significant activation of the contralateral primary motor cortex in 95% (19/20) of the brain tumour patients (hand activation 13/13, foot activation 6/7), showing a mean increase in normalised [18F]FDG uptake of 20.5% +/- 5.2% (hand activation task) and 17.2% +/- 2.5% (foot activation task). Additionally detected activation of the ipsilateral primary motor cortex was interpreted as a metabolic indication for interhemispheric compensational processes. Evaluation of the PET findings by cortical stimulation yielded a 94% sensitivity and a 95% specificity for identification of motor-associated brain areas. In conclusion, the findings indicate that a relatively simple and clinically available [18F]FDG PET activation protocol enables a sufficiently precise assessment of the local relation between the intracranial tumour and the adjacent motor cortex areas and may facilitate the presurgical planning of tumour resection.     

Localisation of motor areas in brain tumour patients: a comparison of preoperative [18F]FDG-PET and intraoperative cortical electrostimulation

Assessment of the exact spatial relation between tumour and adjacent functionally relevant brain areas is a primary tool in the presurgical planning in brain tumour patients. The purpose of this study was to compare a preoperative fluorine-18 fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET) activation protocol in patients with tumours near the central area with the results of intraoperative direct cortical electrostimulation, and to determine whether non-invasive preoperative PET imaging can provide results equivalent to those achieved with the invasive neurosurgical "gold standard". In this prospective study, we examined 20 patients with various tumours of the central area, performing two PET scans (each 30 min after i.v. injection of 134-341 MBq [¹⁸F]FDG) in each patient: (1) a resting baseline scan and (2) an activation scan using a standardised motor task (finger tapping, foot stretching). Following PET/MRI realignment and normalisation to the whole brain counts, parametric images of the activation versus the rest study were calculated and pixels above categorical threshold values were projected to the individual MRI for bimodal assessment of morphology and function (PET/MRI overlay). Intraoperative direct cortical electrostimulation was performed using a Viking IV probe (5 pulses, each of 100 µs) and documented using a dedicated neuro navigation system. Results were compared with the preoperative PET findings. PET revealed significant activation of the contralateral primary motor cortex in 95% (19/20) of the brain tumour patients (hand activation 13/13, foot activation 6/7), showing a mean increase in normalised [¹⁸F]FDG uptake of 20.5%LJ.2% (hand activation task) and 17.2%DŽ.5% (foot activation task). Additionally detected activation of the ipsilateral primary motor cortex was interpreted as a metabolic indication for interhemispheric compensational processes. Evaluation of the PET findings by cortical stimulation yielded a 94% sensitivity and a 95% specificity for identification of motor-associated brain areas. In conclusion, the findings indicate that a relatively simple and clinically available [¹⁸F]FDG PET activation protocol enables a sufficiently precise assessment of the local relation between the intracranial tumour and the adjacent motor cortex areas and may facilitate the presurgical planning of tumour resection.     

H(2)(15)O PET validation of steady-state arterial spin tagging cerebral blood flow measurements in humans.

Steady-state arterial spin tagging approaches can provide quantitative images of CBF, but have not been validated in humans. The work presented here compared CBF values measured using steady-state arterial spin tagging with CBF values measured in the same group of human subjects using the H(2)(15)O IV bolus PET method. Blood flow values determined by H(2)(15)O PET were corrected for the known effects of incomplete extraction of water across the blood brain barrier. For a cortical strip ROI, blood flow values determined using arterial spin tagging (64+/-12 cc/100 g/min) were not statistically different from corrected blood flow values determined using H(2)(15)O PET (67+/-13 cc/100 g/min). However, for a central white matter ROI, blood flow values determined using arterial spin tagging were significantly underestimated compared to corrected blood flow values determined using H(2)(15)O PET. This underestimation could be caused by an underestimation of the arterial transit time for white matter regions.     

Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [64Cu]-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and [64Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that [62Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.     

Development of method to estimate delay time for arterial imput function with [15O]CO2-PET study using sinogram data and attenuation map

The difference in tracer arrival times between the external radiation detector and the brain following administration of radioactivity (delay time) must be estimated correctly in order to quantitatively measure regional cerebral blood flow (rCBF) with positron emission tomography and [15O]H2O by autoradiographic method. Instead of intervenous injection of [15O]H2O, bolus inhalation of [15O]CO2 gas is sometimes used to simplify the measurement of rCBF. In the case of [15O]CO2, radioactive gas in mask and nasal cavity contributes large artifact on the sinogram data and it is difficult to estimate delay time from the sinogram data. In this paper, we proposed a new method to estimate the delay time using the sinogram data and the attenuation map (attenuation weighted sinogram method). In the present method, the attenuation map was used to eliminate the effect of the gas outside the brain region from the sinogram data. For the validation of the present method, PET data with [15O]CO2 (n = 10) were analyzed. Three methods, namely the image method, the sinogram method and the attenuation weighted sinogram method were used to estimate the delay time. The estimated delay times and calculated rCBF images by three methods were compared. Due to the radioactivity outside of the brain, the sinogram method significantly overestimated the delay time and thus underestimated the rCBF value compared with the image base method. On the other hand, there were good agreements between the delay times estimated by the attenuation weighted sinogram method and the image method. The present method can eliminate the effect of the radioactivity outside of the brain on the sinogram data and estimate the delay time accurately and fast enough for clinical use.     

Relationships between oxygen and glucose metabolism in human liver tumours: positron emission tomography using (15)O and (18)F-deoxyglucose

BACKGROUND: Recently, investigators have measured glucose utilization in liver tumours using F-deoxyglucose positron emission tomography (FDG PET) in order to characterize tumours and predict therapeutic effects. However, the detectability of liver tumours by this method remains unclear. In addition, no study has examined the association between oxygen and glucose metabolism in liver tumours using PET. AIM: To evaluate these associations in human liver tumours in vivo using O and FDG. METHODS: Thirteen patients with liver tumours were studied: six with hepatocellular carcinoma (HCC), one with cholangiocarcinoma (CCC) and six with metastatic colon cancer (MET). We measured regional tumour blood flow (Ft), regional oxygen extraction fraction (OEF) and regional metabolic rate of oxygen (MRO2) using O PET. Using FDG PET, we determined a standardized uptake value (SUV) for liver tumours as an index of glucose metabolism. RESULTS: The mean values (mean+/-SE) for Ft, OEF, MRO2 and SUV were 42.5+/-7.0 ml x (100 g) x min, 43.4+/-4.9%, 2.57+/-0.39 ml x (100g) x min and 4.01+/-0.36, respectively. SUV for MET (4.44+/-0.48) was higher than that for HCC (3.52+/-0.59), and the blood flow in MET [31.4+/-4.1 ml x (100 g) x min] was lower than that in HCC [57.1+/-12.4 ml x (100 g) x min]. Significant negative correlations were noted between MRO2 and SUV (r=-0.741, P=0.004), and between Ft and SUV (r=-0.713, P=0.006). No correlation was apparent between Ft and OEF (r=-0.348, P=0.24), or between OEF and SUV (r=-0.023, P=0.94). CONCLUSION: O and FDG PET showed a significant negative correlation between MRO2 and SUV in human liver tumours. In addition, MRO2 depends on Ft rather than on OEF.     

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Voxel- and ROI-based statistical analyses of PET parameters for guidance in the surgical treatment of intractable mesial temporal lobe epilepsy

OBJECTIVE: Positron emission tomography (PET) can be used to locate epileptic foci in patients with mesial temporal lobe epilepsy (MTLE) by measuring multiple parameters of the brain. We investigated a series of patients with MTLE using PET measurements of three parameters: the cerebral blood flow measured with [15 O] H2O, the uptake of [18F] fluorodeoxyglucose (FDG), an index of the cerebral metabolism rate of glucose, and the distribution volume (DV) of [11C] flumazenil (FMZ), an index of the binding potential of central benzodiazepine receptor. We compared predictive values obtained from two methods: a voxel-based statistical analysis using statistical parametric mapping (SPM) and an asymmetry index obtained by placing regions of interest (ROIs) on PET images. METHODS: Preoperative PET data of 11 patients with surgically confirmed MTLE were retrospectively examined. In the voxel-based analysis, the PET data were analyzed using SPM99 by statistically comparing the voxel values of PET parameters between individual patients and the mean values of 12 normal volunteers. Voxels with values significantly lower than the normal control values were mapped on a standard brain atlas. In the ROI-based analysis, the asymmetry index was calculated to depict ROIs with abnormally decreased values when compared with the contralateral side. RESULTS: (1) Statistical parametric mapping and ROI analyses of the FDG uptake correctly determined epileptic temporal lobe in 73% and 82%, respectively. (2) The decreased DV of FMZ depicted by SPM revealed the mesial temporal pathology in 91%. CONCLUSIONS: Positron emission tomography measurement of FDG uptake was most sensitive in detecting the side of the epileptic focus. On the other hand, SPM analysis of the DV of FMZ was the most sensitive method for delineating the actual epileptic focus.     

Quantification of cerebral blood flow and oxygen metabolism with 3-dimensional PET and 15O: validation by comparison with 2-dimensional PET.

Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET. METHODS: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET. RESULTS: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent. CONCLUSION: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.     

Brain perfusion CT compared with 15O-H2O PET in patients with primary brain tumours

Purpose

Perfusion CT (PCT) measurements of regional cerebral blood flow (rCBF) have been proposed as a fast and easy method for identifying angiogenically active tumours. In this study, quantitative PCT rCBF measurements in patients with brain tumours were compared to the gold standard PET rCBF with ¹⁵O-labelled water (¹⁵O-H₂O).

Methods

On the same day within a few hours, rCBF was measured in ten adult patients with treatment-na?ve primary brain tumours, twice using ¹⁵O-H₂O PET and once with PCT performed over the central part of the tumour. Matching rCBF values in tumour and contralateral healthy regions of interest were compared.

Results

PCT overestimated intratumoural blood flow in all patients with volume-weighted mean rCBF values of 28.2?±?18.8?ml min^?1 100?ml^?1 for PET and 78.9?±?41.8?ml min^?1 100?ml^?1 for PCT. There was a significant method by tumour grade interaction with a significant tumour grade rCBF difference for PCT of 32.9?±?15.8?ml?min^?1 100?ml^?1 for low-grade (WHO I + II) and 81.5?±?15.4?ml?min^?1 100?ml^?1 for high-grade (WHO III + IV) tumours, but not for PET. The rCBF PCT and PET correlation was only significant within tumours in two patients.

Conclusion

Although intratumoural blood flow measured by PCT may add valuable information on tumour grade, the method cannot substitute quantitative measurements of blood flow by PET and ¹⁵O-H₂O PET in brain tumours.     

Functional imaging of malignant paragangliomas and carcinoid tumours

Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared ¹²³I-MIBG, ¹¹¹In-[D-Phe¹]-DTPA-octreotide and ¹⁸F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of ¹¹¹In-[D-Phe¹]-DTPA-octreotide and ¹²³I-MIBG. Whole-body PET scans were performed 45 min after injection of ¹⁸F-FDG. ¹¹¹In-[D-Phe¹]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, ¹⁸F-FDG PET was positive in 11/15 patients and identified 107 lesions and ¹²³I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. ¹⁸F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.     

O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours

Purpose The aim of this study was to evaluate the differential uptake of O-(2-[¹⁸F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours.Methods Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FET_max).Results FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FET_max between the two categories was observed only in the first image frame (0–10 min p.i.), with FET_max=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30–40 min p.i.), with FET_max=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame).Conclusion These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.     

Quantification of regional cerebral blood flow in rats using an arteriovenous shunt and micro-PET

IntroductionMeasurement of regional cerebral blood flow (rCBF) in rodents can provide knowledge of pathophysiology of the cerebral circulation, but generally requires blood sampling for analysis during positron emission tomography (PET). We therefore tested the feasibility of using an arteriovenous (AV) shunt in rats for less invasive blood analysis.MethodsSix anesthetized rats received [¹⁵O]H₂O and [¹⁵O]CO PET scans with their femoral artery and vein connected by an AV shunt, the activity within which was measured with a germanium ortho-oxysilicate scintillation detector. The [¹⁵O]H₂O was intravenously injected either at a faster or slower injection rate, while animals were placed either with their head or heart centered in the gantry. The time–activity curve (TAC) from the AV shunt was compared with that from the cardiac ventricle in PET image. The rCBF values were calculated by a nonlinear least-square method using the dispersion-corrected AV-shunt TAC as an input.ResultsThe AV-shunt TAC had higher signal-to-noise ratio, but also had delay and dispersion compared with the image-derived TAC. The delay time between the AV-shunt TAC and image-based TAC ranged from 11 to 21 s, while the dispersion was estimated to be ～5 s as a time constant of the dispersion model of exponential function, and both were properly corrected. In a steady-state condition of [¹⁵O]CO PET, the blood activity concentration by AV-shunt TAC was also comparable in height with the image-based TAC corrected for partial volume. Whole-brain CBF values measured by [¹⁵O]H₂O were 0.37±0.04 (mean±S.D.) ml/g/min, partition coefficient was 0.73±0.04 ml/g, and the CBF varied in a linear relationship with partial pressure of carbon dioxide during each scan.ConclusionsThe AV-shunt technique allows less invasive, quantitative and reproducible measurement of rCBF in [¹⁵O]H₂O PET studies in rats than direct blood sampling and radioassay.     

Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and

Radiolabelled ganciclovir analogues have shown promise as imaging agents to detect herpes simplex virus thymidine kinase (HSVtk) expression. This study evaluated the use of positron emission tomography (PET) imaging with 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG) to assess gene transfer into tumours. HSVtk-positive and HSVtk-negative cell lines were first treated in vitro with [18F]FHPG. To assess the efficacy of PET in detecting HSVtk expression following in vivo gene transfer, mice were injected intravenously with an adenovirus encoding HSVtk (Ad.HSVtk), a control vector (Ad.Bgl2) or saline. Subcutaneous human glioma xenografts were grown in mice and treated by direct injection of Ad.HSVtk or Ad.Bgl2. Imaging was performed 48 h after transduction. Similar experiments were performed using Fischer rats implanted with syngeneic tumours. The presence of the HSVtk protein was confirmed by immunohistochemistry. Biodistribution studies were also obtained in 14 naive mice. In vitro studies showed high and specific uptake of [18F]FHPG in HSVtk-positive cell lines, with an uptake ratio of up to 27:1. PET imaging and direct counting of major organs demonstrated HSVtk-specific tracer retention. In mice, HSVtk-positive tumours retained 3.4% dose/gram as compared to 0.6% for control tumours (P=0.03). They were clearly seen on the PET images as early as 100 min post injection. Similar results were obtained with syngeneic rat tumours. Biodistribution studies demonstrated the rapid distribution and clearance of the tracer in all major organs. Our results demonstrate that PET imaging of HSVtk gene transfer to tumours is feasible and is highly specific for HSVtk expression.     

Feasibility of imaging photodynamic injury to tumours by high-resolution positron emission tomography

One early effect of the treatment of tumours by the new modality photodynamic therapy (PDT) is a reduction in tumour glucose levels. We have employed the widely used positron-emitting glucose analogue flurorine-18 fluoro-2-deoxy-d-glucose ([¹⁸F]-FDG), to determine whether, in principle, PDT-induced injury might be delineated non-invasively and quantitatively by positron emission tomography (PET). The scanner was of the high-density avalanche-chamber (HIDAC) type with a resolution of 2.6 mm. Subcutaneous T50/80 mouse mammary tumours, sensitised by haematoporphyrin ester, were illuminated by graded doses of interstitial 630 nm light. Thirty hours later, any remaining viable tumour was detected (a) by region-of-interest analysis of the PET images and (b) by gamma counting the excised tumour. PET measurements of % uptake of [¹⁸F]-FDG into tumour correlated closely with ex vivo gamma counting (slope=0.976, r²⁼0.995), validating the in situ method. Uptake into untreated, control tumours was 3.8%±1.1% of the injected activity. Uptake of [¹⁸F]-FDG into treated tumours decreased by 0.7% for every 100 mm³ reduction in remaining viable histological volume. Outcome was further compared with that measured by (a) T2-weighted proton imaging on a 4.7-T magnetic resonance imaging (MRI) system and (b) histological analysis of subsequently sectioned tumours. PET using [¹⁸F]-FDG described the absolute volume of surviving tumour histological mass to the same degree as high-resolution MRI. The conclusion of these initial studies is that PET with [¹⁸F]-FDG, although non-specific, quantitatively described at early times the extent of tumour destruction by PDT. Received 1 April and in revised form 9 May 1998     

A simple effective method for estimating the [18O] enrichment of water mixtures.

Isotopically enriched water, [18O] H(2)O, recovered from the synthesis of [18F] fluorine-labelled PET radiopharmaceuticals, is frequently diluted with natural water, [16O] H(2)O. The extent of isotope dilution limits the usefulness of the recovered water. A simple method for determining the [18O] enrichment of water mixtures could aid PET cyclotron facilities to calculate the [18F] yields to be expected when the recovered [18O] H(2)O is reused. A gravimetric method (repeatability for high enrichment +/-0.3% [18O], detection limit approximately 2% [18O] enrichment) is described.     

PET radiopharmaceuticals in Europe: Current use and data relevant for the formulation of summaries of product characteristics (SPCs)

The increasing use of radiopharmaceuticals for positron emission tomography (PET) has come to the attention of regulatory bodies. In order to help authorities in all aspects, the EANM has formed a task group for licensing PET radiopharmaceuticals; this group has surveyed the use of these compounds in Europe by a questionnaire. The number of PET centres that responded to the questionnaire was 26, which included more than 90% of the larger European PET centres. The survey showed that 2-[¹⁸F]fluoro-2-deoxyglucose is by far the most important PET radiopharmaceutical with more than 200 applications per week, followed by [¹⁵O]water, [¹⁵O]carbonmonoxide, [¹³N]ammonia, [¹¹C]-l-methionine, andl-6-[¹⁸F]fluoro-DOPA. More than 25 other PET radiopharmaceuticals are in regular use, however, at rather low application frequencies. The data were used by the European Pharmacopoeia Commission for its priority rating for requesting the formulation of monographs. Since it is likely that group registrations will be issued by authorities for the PET radiopharmaceuticals, relevant data on toxicity and dosimetry for the formulation of summaries of product characteristics have been collected by the task group as well.