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Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-99m-sestamibi (Tc-99m-MIBI) and metabolism using F-18-fluorodeoxyglucose (F-18-FDG) in a single study. The prerequisite is that the Tc-99m-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered 99mTc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-99m-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-99m-MIBI and 185 MBq of F-18-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-99m-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-18-FDG and Tc-99m-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r = 0.93, P

Positron Emission Tomography (PET) is a method for determining biochemical and physiological processes in vivo in a quantitative manner. The most commonly used radionuclides are C-11, N-13, O-15 and F-18, with respective half-lives of approximately 20 min, 10 min, 2 min, and 110 min. F-18 labeled FDG (fluoro-2-deoxy-D-glucose) is now the most frequently used radiopharmaceutical and finds its application prominently in the field of oncology. Originally, the production of these radionuclides was performed with the existing accelerators, designed for nuclear physics, but with increasing interest in the PET methodology specially designed PET-production cyclotrons became available. The nuclear reactions involved are (p,n), (d,n), (p,alpha) and (d,alpha) and the thresholds for the nuclear reactions involved are 5 to 6 MeV. Based on these values and on other parameters, a proton 15 to 20 MeV cyclotron is often chosen. Since the half-life of a radionuclide limits the production time, the maximum beam current is an important parameter, together with the target construction, for the ultimate yield obtainable. In the development of special PET production cyclotrons, attention has also been paid to improve the extraction efficiency and the possibility of multiple extractions by designing negative ion cyclotrons. Commercial cyclotrons can often be acquired as an easy to operate integrated radionuclide production unit including targetry and some units. Regional FDG factories are nowadays being created to fulfil the demand for PET radiopharmaceutics. The possible choices in commercially available cyclotrons for the production of PET radionuclides will be discussed.

Regional cerebral blood flow was assessed during reaching movements with either target or finger selection. Measurements were performed with positron emission tomography in normal subjects. We thus identified two patterns of cerebral activation representing parietal command functions based on either external space or body scheme information. Directing the right-hand index finger toward one target dot in an array of five was related to activations distributed over dorsal extrastriate visual cortex (putative area V3A), along the parieto-occipital sulcus (putative V6/V6A) and the posterior intraparietal sulcus (IPS). Right-hemisphere dominance was present at the occipital extension of posterior IPS. Positioning one right-hand finger of five on the middle target dot was related with anterior IPS activation, extending over the marginal gyrus of the left inferior parietal lobe. The latter indicated a parietal role in prehension, independent of the shape of the target reached for. In both conditions of the reaching task, instructions for movement were auditorily given by random numbers 1 to 5, thus excluding visual cueing. The observed lateralization of movement-related parietal functions helps to explain neurological symptoms such as ideomotor apraxia and spatial hemineglect. (C) 2001 Academic Press.

In previous EEG experiments we have presented a time estimation task to our subjects, who bad to press a button with either the left or right index finger 3 s after an auditory warning stimulus (WS). Two seconds later a visual Knowledge of Results (KR) stimulus was presented on a screen in front, informing them about whether the movement had been made in the correct time window (a vertical line), whether it was too early (a minus sign) or too late (a plus sign). The potential distribution underlying the anticipatory attention for the KR stimulus suggested a right hemisphere network in which the prefrontal cortex, the insula Reili and the parietal cortex were involved. In the present positron emission tomography (PET) activation study we aimed to further localize the exact positions of these regions, using the same paradigm. Two conditions were compared in which the WS had to be followed by a button press with the left index finger. In experimental condition A, subjects received true information about their performance, while in condition B false information was given, utilizing the same stimuli, but randomly, thus without any relation to the actual performance. In both conditions identical stimuli were presented and identical movements were made. Therefore we applied statistical parameter mapping (SPM) for comparison of condition A with B in order to identify regional increases in perfusion related to the anticipation and use of the KR. We found in line with our predictions a right hemisphere activation of (1) BA45, (2) the junction of the posterior insula with the temporal transverse gyrus and (3) the posterior part of the parietal cortex. This activation pattern was accompanied by a better performance due to KR. A second, though not predicted, effect was the increase in correct responses during the last two sessions compared to the first two sessions, independent of KR. This learning effect was accompanied by an activation of BA46 and the supplementary motor area (SMA), again in the right hemisphere. Summarizing, two different prefrontal areas in the right hemisphere were activated: a more ventral area, related to the use of external stimuli providing feedback about a past performance, in order to produce movements in time, and another mid-dorsal one, related to temporal programming on the basis of internal cues.

The distribution of increased regional cerebral blood flow (rCBF) related to visuomotor coordination was studied by means of positron emission tomography (PET) in normal subjects. An experimental condition, in which a vertically presented zigzag figure had to be copied in a horizontal orientation, was compared with a control condition in which the same horizontal drawing was made, guided by a horizontally presented example. Cognitive components dealing with the mismatch in visual orientation resulted in activation of (i) right dorsal premotor cortex, (ii) right posterior parietal cortex, (iii) visual cortex (area V1) and (iv) left fusiform gyrus. In a second experiment, conditions were compared in which the same horizontal zigzag figure was copied in either a vertical or a horizontal orientation. Now, the motor components of the transformation of orientation appeared to be associated only with left premotor cortex activation. The differential distribution of activations is regarded to reflect the selective effort to cope with either the visual or the motor component of spatial incongruity, and indicates specialization for perceptual and executive components in visuomotor control. We propose that the perceptual component of visuomotor transformation in our experiment relates to a realignment of the coordinates of a percept to an internally defined coordinate system. The executive component relates to guidance of movement within an internal representation of space. In a preceding behavioural experiment, a majority of patients with Parkinson's disease (PD) failed on the task in which they had to make a horizontal copy of a vertically presented picture. This finding may suggest a deficit in the maintenance of an internal spatial representation to guide movement. (C) 1999 Elsevier Science B.V. All rights reserved.

By using positron emission tomography, we aimed to identify cerebral foci of neuronal activation associated with the initiation of a specific motor program. To that end, a state of repeatedly alternating in- and antiphase of bimanual flexion and extension movements was compared with similar movement responses except phase changing. This comparison provided the opportunity to eliminate confounding effects of attention and simple movements. Change between the two bimanual motor programs was related with activation at the posterior border of the left angular gyrus, the right precuneus, and the right premotor and right medial prefrontal cortex. In a subsequent experiment, with attention and random movements as additional variables, activation at the posterior border of the left angular gyrus was found at the same significance level. This posterior parietal activation may indicate an equivalence with the coding of intention in monkey posterior parietal cortex. Lesion of the left posterior parietal cortex in human gives rise to left-right disorientation and ideomotor apraxia. Our results may support the view that these symptoms reflect the inability to transpose a motor plan to the representation of a personal body scheme. Activation of the right premotor and right medial prefrontal cortex was related both to the change between motor programs and to the condition with strictly regular movement in which no additional responses were made to randomly presented signals. This is consistent with the concept that motor preparation is associated with both the selection of internally instructed movements and the suppression of irrelevant environmental stimuli. (C) 1999 Academic Press.

Background, The aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography(PET)scans. Methods. We retrospectively analyzed the data of 20 patients who under,vent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA), Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard. Results. Both QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y = 0.90 x x-5.9, r = 0.86, P

Positron Emission Tomography (PET) is a method for determining biochemical and physiological processes in vivo in a quantitative way. This includes the measurement of the pharmacokinetics of labeled drugs and the measurement of the effects of drugs and/or therapy on metabolism. Also deviations of normal metabolism can be measured and insight in biological processes responsible for diseases can be obtained. To accomplish these measurements a multi-disciplinary team is necessary for the expertise in the fields of radionuclide production, radiochemistry, pharmacy, medicine, nuclear imaging and data analysis.

A story told by his mother was presented on tape to a trauma patient in persistent vegetative state (PVS). During auditory presentation, measurements of regional cerebral blood flow (rCBF) were performed by means of positron emission tomography (PET). Changes in rCBF related to this stimulus condition, as compared to presenting non-word sound, were evaluated by means of statistical parametric mapping (SPM). This analysis indicated activation of rostral anterior cingulate, right middle temporal and right premotor cortices, which may reflect appropriate cortical involvement in processing emotional attributes of sound or speech. (C) 1997 Elsevier Science B.V.

The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG, Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). Conclusion: in this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease, SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.

After acute cerebral stroke, the (peri-) infarct tissue is characterized by calcium (Ca)-mediated neuronal damage and inflammatory processes. Monitoring Ca-mediated damage using the isotope cobalt-55 (Go) as a Ga-tracer may enable PET-imaging of this tissue. Since the fate of (peri-) infarct tissue determines clinical outcome, Go-PET may have prognostic value in stroke. Six stroke patients were examined with Go-PET, MRI and a middle cerebral artery (mca) stroke scale (Orgogozo). In every patient? specific Go-accumulation in the appropriate brain region was seen, irrespective of the integrity of the blood-brain barrier. This pilot study suggests Go-PET as a diagnostic tool in stroke, which may provide additional information on the clinical outcome. Validation of method in larger patient series is necessary. (C) 1997 Elsevier Science B.V.

Background: It is often difficult to detect a local recurrence of soft-tissue sarcomas due to disturbance of the normal anatomy by previous surgery and radiotherapy. The aim of this study was to assess the value of positron emission tomography (PET) with [F-18]fluoro3-deoxy-D-glucose (FDG) for detecting local recurrences. Methods: In the period 1992-1995, 17 patients with proven or suspected local recurrence of soft-tissue sarcoma were examined using FDG-PET. Fifteen of these patients were ultimately proven to have a recurrence. Results: Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter 0.5 cm) were as easily visible as large lesions (maximum diameter 20 cm). In one patient the PET scan was positive, but the recurrence could not be proven histologically. Recurrence was proven 1 year later. A recurrent low-grade liposarcoma was not visualized. The two patients with benign lesions had a negative PET scan. The mean glucose metabolic rate was calculated to be 13.2 mu mol/100 g/min (range 1.9-28.4). A correlation was found between the histological malignancy grade and the metabolic rate (p

System parameters as spatial resolution, sensitivity, singles and coincidence count rates, signal to noise (S/N) ratio have been measured with positron emitting radiopharmaceuticals in a Siemens MultiSpect2 system with 511 keV collimators, a Siemens ZLC dual-headed uncollimated rotating gamma camera system operated in coincidence mode and a Siemens Ecat 951/31 PET ring system. From these measurements it is evident that the sensitivity and spatial resolution of PET systems are superior to those achieved by SPECT systems. The performance of PET ring systems is superior compared to dual-headed coincidence systems especially if count rate capability and accidental coincidences are considered. The better energy resolution of NaI in comparison with EGO results in a lower scatter fraction at the same energy window. An absolute quantitation is only possible with PET ring systems with an individual attenuation correction.

The isotopes Co-55 and Co-57 have been evaluated for PET and SPECT imaging in several clinical brain studies. For clinical application of cobalt, it is important to know the delivered radiation dose. The biodistribution of Co-55 in both rat and humans after intravenous (bolus)-administration was studied. Based on pharmacokinetic data, radiation dose calculations according to the MIRD system are presented, By combining present measurements with literature data on (CoCl2)-Co-60, the radiation dose delivered by (CoCl2)-Co-56 (T-1/2 78.8 days) and (CoCl2)-Co-57 (T-1/2 = 270 days) could be assessed. Methods: Whole-body Co-PET was performed in two healthy volunteers and one rat after intravenous injection of 37 and 3.7 MBq (1 resp, 0.1 mCl) Co-55, respectively. Blood samples were withdrawn during 300 min in humans. In seven rats the Co-55-biodistribution was determined by postmortem analysis. The residence time of the liver (critical organ) was determined in rats and humans. Blood partition-data of Co-55 were assessed resulting in basic pharmacokinetic data in humans. Based on these kinetic data, radiation dose was calculated using the MIRD protocol. Results: In both the humans and the rat, the liver and bladder retained the highest fractions of Co-55 (about 50% resp. 40% of the administered dose), The liver residence time in humans was 8.6 hr. The free fraction Co-55 in the human plasma was at maximum 12%. The total-body mean transit time was 152 min. The volume of the central compartment = 2.8 liter and the steady-state distribution volume = 48 liter. Conclusion: From these results, according to the WHO recommendations for class II studies, 22.2 MBq (0.6 mCi) Co-55 and 14.8 MBq (0.4 mCi) Co-57 (excluding any radionuclide contamination) can be used.

We investigated FDG-PET in patients undergoing hyperthermic isolated limb perfusion (HILP) with rTNF-alpha, rIFN-gamma and melphalan for locally advanced soft-tissue sarcoma of the extremities. Methods: Twenty patients (11 women, 9 men; aged 18-80 yr, mean age 49 yr) were studied, FDG-PET studies were performed before, 2 and 8 wk after HILP. After the final PET study, the tumor was resected and pathologically graded, Patients with pathologically complete response (pCR) showed no viable tumor after treatment, Those with pathologically partial response (pPR) showed various amounts of viable tumor in the resected specimens. Results Seven patients showed a pCR (35%) and 12 patients showed a pPR (60%). In one patient, pathological examination was not performed (5%). The pre-perfusion glucose consumption in the pCR group was significantly higher than in the pPR group (p

Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2-propanol (S-1'-[F-18]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C-18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.

We studied the potential of L-[1-C-11]tyrosine ([1-C-11]Tyr) and L-[methyl-C-11]methionine ([Me-C-11]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models. Methods: In the liver and plasma of control and cycloheximide-treated mice injected with [1-C-14]Tyr and [Me-H-3]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with C-11-labeled analogs and PET. Results: In mice, liver uptake of [Me-H-3]Met was over twice as large as that of [1-C-14]Tyr. Similar uptake patterns of the C-11-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, similar to 69%-73% of the C-14 was detected in the protein fraction, whereas similar to 65%-70% of the H-3 was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were similar to 73%-76% for C-14 and similar to 36%-46% for H-3. Gel-filtration analysis suggested that 80% of the C-14-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide the liver uptake of the [1-C-14]Tyr and the protein-incorporation of C-14 in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-H-3]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction. Conclusion: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-C-11]Met mainly reflects phospholipid synthesis through the transmethylation process.

PET with F-18-fluoro-2-deoxy-D-glucose (FDG) was used to study soft-tissue lesions, The goals of the study were to establish FDG uptake in soft-tissue sarcoma, to determine the sensitivity of this technique, to investigate the correlation between histologic grade and glucose consumption and to determine whether FDG-PET can discriminate between benign and malignant lesions, Methods: PET imaging was performed in 18 patients with soft-tissue sarcoma and 4 patients with a benign soft-tissue lesion. Glucose consumption in the tumors was calculated using Patlak's graphical analysis with an assumption made for the lumped constant. Standardized uptake values also were calculated. Results: All soft-tissue sarcomas were clearly depicted, The median glucose consumption was 13.0 mu mole/100 g/min (range 2.9-41.8 mu mole/100 g/min). A correlation was found between glucose metabolism and the histopathologic malignancy grade, Such a correlation was not demonstrated for the standardized uptake values, One benign lesion was also visualized. Benign lesions were not visualized in two patients and in the remaining patient an equivocal scan was obtained, Benign lesions could be distinguished from high-grade malignant lesions but not consistently from lesions with low or intermediate malignancy grades, Conclusion: PET with FDG is an effective technique to visualize soft-tissue sarcomas. We found a sensitivity of 100%, There is a correlation between glucose metabolic rate and tumor malignancy grade. FDG appears to be unsuitable for discriminating benign lesions from soft-tissue sarcomas with low or intermediate malignancy grades.

Multiple sclerosis (MS) is an immune-mediated disease of the white matter in the brain that can have a progressive course. However, the progression of relapsing-remitting (RR) MS into relapsing-progressive (RP) MS might represent a more fundamental change in disease activity, i.e. decay of vulnerable neurons and oligodendrocytes. In RP-MS, this may imply that the major loss of brain tissue structure is caused by a combination of demyelination and cellular loss, both of which are likely to cause disability in MS. We used the PET isotope cobalt-55 (Go) as a calcium (Ca) tracer to visualize brain tissue damage, based on the fact that Ca influx is essential in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine whether Co-PET detects any RP-MS lesions and, if so, to assess any correlation with the progression rate (PR) of the disease and with MS lesions as detected by MRI. Seven RP-MS patients (Poser) with EDSS > 4.0 (Kurtzke) and 7 healthy controls underwent MRI (Miller, Barkhof) and Co-PET. Comparison of both image modalities was made by merging. Co-PET lesion frequency was assessed and correlated with the PR of the disease. Co-PET demonstrated significantly more lesions in the MS brain than in the healthy brain, both periventricular and cortical. Every single MRI lesion could be retrieved as a Co-PET lesion. The Co-PET lesion frequency correlated significantly with PR. Our pilot study possibly suggests Co-PET as a tool in estimating disease activity in RP-MS. Validation of method in a larger patient group (RP-MS vs PR-MS vs healthy controls) will be necessary.

In the last decades increasing information has become available on changes in cardiac receptors during pathophysiological circumstances. With the advent of positron emission tomography (PET) imaging it is now theoretically possible to measure receptor density noninvasively in vivo. In the field of sympathetic innervation and postsynaptic cardiac s-adrenoceptors in the heart, the first data using the PET technique have been published. Beta-adrenoceptors have been quantified by in vitro binding assays and changes in s-adrenoceptor density have been associated with congestive heart failure,1, 2 myocardial ischemia,3, 4 cardiomyopathy,5, 6 valvular diseases,7 hypertension,8 diabetes,9, 10 hyperthyroidism11 and chronic drug administration.12, 13 Cardiac s1adrenoceptors exert positive inotropic, lusitropic, and chronotropic effects, whereas cardiac s2-adrenoceptors mainly have positive chronotropic and vasodilatory effects. Alteration in number of these receptors will affect cardiac function, especially since the human heart has a small receptor reserve for s-agonists.2

Changes in receptor populations may be early markers of disease, or indicators of the therapeutic success. A large research effort is therefore directed towards tomographic imaging of receptors and quantitative interpretation of these images in terms of receptor densities. Before human studies are possible, putative receptor-binding radiotracers should be thoroughly tested. The testing of a radioligand for imaging purposes includes two distinct areas of research: 1. It should be demonstrated that the compound binds preferentially to the chosen receptor in intact animals or humans; 2. An experimental protocol should be designed that allows changes in receptor density (e.g. due to disease) to be determined with sufficient accuracy and sensitivity. This chapter discusses the use of labeled beta-adrenoceptor ligands for cardiac imaging, as an example of receptor imaging in general.

Methods: The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. Results: PET with F-18-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. Conclusion: FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.

To evaluate the possibility of combining proton therapy with Positron Emission Tomography (PET) as a therapy monitor and as a tool for in situ dosimetry during therapy, proton activiation experiments have been performed using a 55 MeV proton beam on two different materials. The 3-D measurements of the induced activity with PET are compared with the calculated dose distribution and with model calculations.

The potential use of PET to monitor radiotherapeutic effects on tumors has been evaluated with L-[1-C-11]tyrosine and 18FDG. Single x-ray doses of 10, 30, or 50 Gy have been applied to rhabdomyosarcoma tumors growing in the flank of rats. Dose-dependent reductions of tracer uptake were registered by PET 4 and 12 days after treatment. These later effects on tracer uptake appeared to correlate with changes in tumor volume. Therefore, PET using L-[1-C-11]tyrosine and 18FDG is suitable to monitor kinetics of tumor growth and tumor regression after radiotherapy. Direct effect on tracer uptake was not observed within 8 hr after irradiation. This indicates that, using PET, early predictions on the outcome of radiotherapy are not possible. When combining a radiation treatment with hyperthermia, radiation-induced inhibition of tumor growth was clearly enhanced. Tracer uptake remained at the pretreatment value, possibly due to invasion of host cells. From these experiments, it can be concluded that it is difficult to monitor a combined treatment of radiation and hyperthermia by PET.

HyPerthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-C-11]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47-degrees-C. Tumor blood flow, as measured by PET with (NH3)-N-13, appeared to be unchanged. The L-[1-C-11]tyrosine uptake data were compared to uptake data of L-[1-C-14]tyrosine and with data on the incorporation of L-[1-C-14]tyrosine into tumor proteins. After intravenous injection, the C-14 data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-C-14]tyrosine into tumor proteins tallied with the L-[1-C-11]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-C-11]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth.

We investigated whether the lack of therapeutic response to long-term and adequate neuroleptic treatment was due to a failure to achieve a blockade of cerebral dopamine receptors. Six chronic schizophrenic and medicated patients (DSM-III-R diagnosis, paranoid or disorganized type) were assessed with the Present State Examination and the Brief Psychiatric Rating Scale. According to the Chouinard Rating Scale there were little extrapyramidal symptoms, although no anticholinergic drugs were given. Plasma levels of the neuroleptics were determined and found in the therapeutic range or higher. Dopamine D2-receptor occupancy was determined with positron emission tomography using C-11-methylspiperone as ligand. There was a more than 95% blockade of the D2 receptors in the striatum. These results indicate that the lack of therapeutic response and extrapyramidal side effects cannot be attributed to an incomplete blockade of cerebral D2 receptors and that the pathogenetic role of these receptors can be questioned in therapy-resistant schizophrenic patients.

Aspects of metabolism in prolactinomas were investigated by positron emission tomography using L-[1-C-11]tyrosine, L-[methyl-C-11]methionine and F-18-fluorodeoxyglucose (18FDG). Using L-[1-C-11]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocryptine. At 18 h after bromocryptine intervention, L-[1-C-11]tyrosine uptake into tumour was reduced with 28% (P

The applicability of five different rodent tumors for experimental PET has been investigated. L-[1-C-11]Tyrosine was a better indicator for the growth activity of the tumors than [F-18]FDG. For experimental PET, the three mice models studied appeared inappropriate; the Lewis lung tumor and the fibrosarcomateous FIO 26 had too low a tyrosine utilization, while the lymphosarcomateous LY showed insufficient tumor-to-background ratios. Of the two rat models, the necrotic Walker 256 carcinosarcoma was less suitable. By using L-[1-C-11]tyrosine, the solid, rhabdomyosarcoma tumor offers good possibilities of monitoring therapeutic interventions with PET.

Based on a double-headed rotating uncollimated scintillation camera system, a positron imaging device was developed. After a rotating data acquisition in coincidence mode, 16 transverse section images are reconstructed by back projection. To obtain a uniform response, a limited angle reconstruction option is incorporated in this process. After correction for the system response by a three-dimensional deconvolution technique, the 16 transverse section images are stored on disk as a standard patient study for further analysis. The system can also be operated in a stationary mode. In this mode longitudinal tomographic images are obtained. Return to single photon scintigraphy is possible by remounting the collimators and by switching off the coincidence electronics.

We monitored 10 patients with unresected (9) or partially resected (1) supratentorial gliomas with C-11-tyrosine position emission tomography (TYR-PET) before and after radiotherapy. TYR-PET tumour volumes were measured using a threshold technique, In seven patients the tumour volume decreased after radiotherapy, although all gliomas persisted on TYR-PET images. In eight patients the tumour protein synthesis rate (PSR) was calculated using a dynamic study protocol in combination with a PATLAK analysis. There were no changes in PSR after radiotherapy, but the PSR was calculated on the remaining tumour volume using the same threshold technique as before therapy, i.e. the decrease in tumour volume was not taken into account. In eight patients the PET data were compared with magnetic resonance spectroscopic imaging (H-1-MRSI) performed simultaneously. Although there was no statistically significant correlation between TYR-PET volume changes and H-1-MRSI choline level we observed a simultaneous decrease in volume and choline in four patients.