Comparison of 99mTc-methoxyisobutyl isonitrile and 201Tl scintigraphy for detection of residual thyroid cancer after 131I ablative therapy.

UNLABELLED: In this study, we compared 99mTc-methoxyisobutyl isonitrile (MIBI) with 201Tl scintigraphy for the detection of residual thyroid cancer not found by 131I scans in patients with increased risk of recurrence after 131I therapy. METHODS: 201Tl and MIBI scans were obtained in 54 patients with negative 131I scans 3-25 y (median 7.9 y) after the first postsurgical 131I therapy. Serum thyroglobulin (Tg) levels were measured while patients were receiving thyroid hormone and again 6 wk after withdrawal of hormone therapy. RESULTS: The overall results were the same for both 201Tl and MIBI imaging, with a sensitivity of 19 of 36 (53%), specificity of 17 of 17 (100%) and accuracy of 36 of 54 (69%). Planar images missed residual cancer in high cervical lymph nodes adjacent to salivary gland activity, in small nodes (<1 cm) deep in the neck or chest and with diffuse pulmonary micrometastases. Serum Tg was elevated in 24 of 36 (67%) patients with residual cancer; 201Tl detected tumor sites in 13 of 24 (54%) of these patients, and MIBI detected tumor sites in 14 of 24 (58%) of these patients. Of the 12 patients who had residual cancer and false-negative serum Tg levels, 6 had true-positive 201Tl and 5 had true-positive MIBI scans. CONCLUSION: 201Tl and MIBI planar imaging yield the same high specificity and positive predictive value for residual thyroid cancer in patients with high-risk profiles and negative radioiodide scans. Both imaging agents detected residual cancer in more than half of the patients in whom conventional staging techniques did not reliably detect either the presence or the extent of residual thyroid cancer and changed the management in patients with surgically resectable cancer.

Prospective investigation of positron emission tomography in lung nodules.

PURPOSE: Solitary pulmonary nodules (SPNs) are commonly identified by chest radiographs and computed tomography (CT). Biopsies are often performed to evaluate the nodules further. An accurate, noninvasive diagnostic test could avoid the morbidity and costs of invasive tissue sampling. We evaluated the ability of fluorine-18 deoxyglucose positron emission tomography (FDG-PET) to discriminate between benign and malignant pulmonary nodules in a prospective, multicenter trial. METHODS: Eighty-nine patients who had newly identified indeterminate SPNs on chest radiographs and CT were evaluated with FDG-PET. PET data were analyzed semiquantitatively by calculating standardized uptake values (SUVs) as an index of FDG accumulation and also by a visual scoring method. PET results were compared with pathology results. RESULTS: Sixty SPNs were malignant and 29 were benign. Using SUV data, PET had an overall sensitivity and specificity for detection of malignant nodules of 92% and 90%. Visual analysis provided a slightly higher, but not statistically significant, sensitivity of 98% and lower specificity of 69%. For SPNs < or = 1.5 cm (34 of 89), the sensitivity and specificity of SUV and visual analysis were 80% and 95% and 100% and 74%, respectively. CONCLUSION: FDG-PET can accurately characterize indeterminate SPNs. PET imaging provides a noninvasive method to evaluate indeterminate SPNs, which can reduce the need for invasive tissue biopsy.

Emotional activation of limbic circuitry in elderly normal subjects in a PET study.

OBJECTIVE: This study was undertaken to identify brain structures associated with emotion in normal elderly subjects. METHOD: Eight normal subjects aged 55-78 years were shown film clips intended to provoke the emotions of happiness, fear, or disgust as well as a neutral state. During emotional activation, regional cerebral blood flow was measured with the use of [15O]H2O positron emission tomography imaging, and subjective emotional responses were recorded. Data were analyzed by subtracting the values during the neutral condition from the values in the various emotional activations. RESULTS: The stimuli produced a general activation in visual pathways that included the primary and secondary visual cortex, involving regions associated with object and spatial recognition. In addition, the specific emotions produced different regional limbic activations, which suggests that different pathways may be used for different types of emotional stimuli. CONCLUSIONS: Emotional activation in normal elderly subjects was associated with increases in blood flow in limbic and paralimbic brain structures. Brain activation may be specific to the emotion being elicited but probably involves complex sensory, association, and memory circuitry. Further studies are needed to identify activations that are specific for emotion.

Emission-based attenuation correction of myocardial perfusion studies.

BACKGROUND: Nonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement. METHODS AND RESULTS: The attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201Tl study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients. CONCLUSIONS: The results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.

Four- to twenty-four-hour uptake ratio: an index of rapid iodine-131 turnover in hyperthyroidism.

UNLABELLED: Rapid thyroidal iodine turnover may contribute to 131I therapy failure in patients with hyperthyroidism. The utility of a 4- to 24-hr 131I uptake ratio was evaluated as an index of thyroidal iodide retention in hyperthyroid patients. METHODS: In 433 hyperthyroid patients, the success of 131I therapy was correlated with the following factors: gender, pretreatment with antithyroid drugs, clinical diagnosis, magnitude of early and late thyroidal 131I uptake values, and the 4- to 24-hr 131I uptake ratio. RESULTS: Of the 433 patients, 362 patients (84%) had a successful outcome after a single therapeutic dose of 131I while 71 (16%) did not. Multiple linear regression analysis revealed that the highest statistically significant predictor of outcome was the 4- to 24-hr 131I uptake ratio (p-value < 0.001); all other factors showed a weaker association. An 131I uptake ratio of > 1 was found in 67 (15%) patients. Thirty-two of these 67 patients (48%) failed 131I therapy, whereas those patients with uptake ratios of < 1.0, only 39/366 (11%) failed 131I therapy. CONCLUSION: The 4- to 24-hr 131I thyroidal uptake ratio is a practical substitute for exact determination of the effective half-life. It identifies patients who are likely to have a rapid 131I turnover without the need for extended thyroid uptake measurements. An 131I uptake ratio of > or = 1 was found in 15% of hyperthyroid patients and was associated with a near 50% 131I therapy failure rate.

Auditory attentional deficits in patients with schizophrenia. A positron emission tomography study.

BACKGROUND: Patients with schizophrenia have frequently been found to perform poorly on tasks requiring selective attention, defined as the ability to focus attention on relevant information while simultaneously ignoring irrelevant stimuli. This study explores the brain mechanisms mediating attentional processing in patients with schizophrenia by measuring their regional cerebral blood flow (rCBF) with positron emission tomography using [15O] water as they performed tasks that differed systematically in attentional demand. METHODS: Ten schizophrenic patients (either neurolepticnaive or withdrawn from medication) (patient group) and 10 normal volunteers (control group) performed auditory target detection tasks. Different types of auditory stimuli (environmental sounds, meaningless speech sounds, and words) were presented either binaurally (ie, same sounds in both ears) or dichotically (simultaneous and different sounds in the 2 ears). In dichotic conditions, subjects were instructed to focus on either their left or right ear. RESULTS: Initial subtraction-based image analyses sought significant rCBF changes anywhere in the brain. Patients consistently had less significant activation than controls in right superotemporal gyrus (STG). Follow-up analyses used regions of interest traced on individual magnetic resonance images to precisely measure rCBF in STG. Unlike controls, patients had higher rCBF in the left STG during all activation conditions. CONCLUSIONS: The abnormal task-related rCBF asymmetry in STG of schizophrenic patients may indicate an isolated temporal lobe deficit, but it may also indicate abnormality in the thalamocortical circuitry mediating selective attention and/or in the brain systems that integrate auditory processing in the 2 hemispheres.

A positron emission tomography study of binaurally and dichotically presented stimuli: effects of level of language and directed attention.

Regional cerebral blood flow (rCBF) was measured using positron emission tomography with oxygen- 15 labeled water as 10 normal subjects listened to three types of auditory stimuli (environmental sounds, meaningless speech, and words) presented binaurally or dichotically. Binaurally presented environmental sounds and words caused similar bilateral rCBF increases in left and right superior temporal gyri. Dichotically presented stimuli (subjects attended to left or right ears) caused asymmetric activation in the temporal lobes, resulting from increased rCBF in temporal lobe regions contralateral to the attended ear and decreased rCBF in the opposite hemisphere. The results indicate that auditorily presented language and non-language stimuli activate similar temporal regions, that dichotic stimulation dramatically changes rCBF in temporal lobes, and that the change is due both to attentional mechanisms and to hemispheric specialization.

Detectability of simulated brain activation using dual radioisotope SPECT based on size and intensity of the focal hyperactivity.

RATIONALE AND OBJECTIVES: Simultaneous single-photon emission computed tomography (SPECT) neuroimaging with both technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and iodine-123 (123I) N-isopropyl-iodoamphetamine is a recently introduced method with potential for assessing activation phenomena in the brain. However, there is limited information on the accuracy of the technique for detecting focal cortical sites of neuroactivation. We determined, in vitro, what levels of activation could be detected as a function of the size of the activated region. METHODS: A Lucite brain phantom was filled with both 123I and 99mTc so as to simulate both a nonactivated state (123I) along with focal sites of activation (99mTc). Simulated activations ranged from 0 to 18% in volumes of 7, 14, 20, and 27 cm3. Imaging was performed with a triple-detector gamma camera using a 10% symmetric window at 140 keV and 10% asymmetric window around 159 keV. No correction was made for gamma cross-talk. To determine whether a simulated activation was "detected," the 99mTc: 123I count ratios in the activated regions were compared by t test with ratios in nonactivated regions of similar volume. Detection sensitivities also were calculated as the fraction of the activated 99mTc: 123I ratios that were greater than the mean + 2 standard deviations of the corresponding nonactivated ratios. RESULTS: All sites of simulated activations of 10% or greater were detected. The detection sensitivity was 100% (95% confidence interval, 90-100%) for the two largest chambers with simulated activations of 13-18%. Activations in the 3-6% range, in the same-sized chambers, were detected with a limited sensitivity (67% with a confidence interval of 45-84%). In the 14-cm3 chamber, simulated activations in the 13-18% range were detected with 90% sensitivity (confidence interval, 74-98%). In general, the detection sensitivity was greater for larger chambers and higher levels of simulated activation. CONCLUSION: We conclude that the dual-radioisotope technique using triple-detector SPECT systems and low-energy all-purpose (LEAP) collimators should be highly reliable for identifying focal brain activations above 13% that cover at least 14 cm3 of brain cortex. Smaller, less intense sites of activation will be detected with reduced frequency. These conclusions are based on our assessment of only the physical parameters involved in this methodology and other factors (e.g., the possibility that the relation between cerebral radiotracer concentration and regional cerebral blood flow) may affect the results obtained with patients.

Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET.

OBJECTIVE: This prospective study was designed to compare the sensitivity and specificity of a relatively simple examination, 201Tl chloride single-photon emission CT (SPECT), with a more complex examination, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), in patients thought to have recurrent brain tumor. Because both agents have been shown to be markers of viable tumor, we hypothesized that their sensitivity and specificity should be the same. SUBJECTS AND METHODS: Nineteen patients with evidence of recurrent tumor on CT or MR images were studied with both 201Tl SPECT and FDG PET imaging. Two patients were examined twice, so a total of 21 studies were evaluated. The 201Tl SPECT and FDG PET examinations were performed on the same day in 17 patients, and the remaining four examinations were done within 1 week of one another. Three reviewers independently interpreted each Tl SPECT and PET scan. Inappropriate regional increases in 201Tl or FDG activity were considered indicative of tumor recurrence. Sensitivity and specificity values were based on biopsy results and clinical follow-up. The final diagnosis was tumor recurrence in 16 cases and radiation necrosis in 5 cases. The relationship of scan results to survival was analyzed. RESULTS: The sensitivity and specificity of the 201Tl examination for detecting tumor recurrence were 11 (69%) of 16 and two (40%) of five, respectively; values for the FDG PET examination were 13 (81%) of 16 and 2 (40%) of 5, respectively. In patients with recurrent tumors less than 1.6 cm in size, results were false-negative in four 201Tl SPECT examinations and three FDG PET studies. All tumor lesions 1.6 cm or larger (n = 8) were detected. Agreement among the three nuclear medicine specialists was complete for each of the 201Tl SPECT scans. There was disagreement on the interpretation of five (24%) of the 21 FDG PET scans, which was resolved by consensus. Scintigraphic findings did not correlate with patients' survival times. CONCLUSION: We were unable to detect a statistically significant difference in sensitivity or specificity between the 201Tl SPECT and FDG PET scans. Both techniques were sensitive for tumor recurrence with lesions less than 1.6 cm or larger. However, given the greater availability, simplicity, and ease of interpretation and the lower cost of the 201Tl SPECT studies, this technique should be considered for detection of tumor recurrence with lesions that are demonstrated to be 1.6 cm or larger on CT or MR examinations.

Captopril-enhanced 99Tcm-MAG3 renal scintigraphy in subjects with suspected renovascular hypertension.

This pilot study was undertaken to generate preliminary data on the accuracy of captopril-enhanced renal scintigraphy with a relatively new radiopharmaceutical, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) for detecting significant renal artery stenosis. Truth data was based either on arteriographic or outcome criteria (blood pressure response to therapy). Twenty-seven subjects with suspected renovascular hypertension were studied with baseline and captopril-enhanced 99Tcm-MAG3 renal scintigraphy and renal arteriography. Scan interpretations were expressed as a probability of a significant renal artery stenosis. Scan interpretations were compared with renal arteriographic results, renal vein renin levels, blood pressure values after renal artery repair, and blood pressure control after 4-26 months of clinical follow-up. Using > or = 50% luminal obstruction on arteriography as the reference standard for renal artery stenosis and a high probability scan representing a positive test, the test sensitivity and specificity were 33 and 97%, respectively (using high or indeterminate probability to represent a positive scan, the test sensitivity and specificity were 67 and 83%, respectively). The negative predictive value of a low probability scan for renal artery stenosis was 80%. However, including a measure of renovascular hypertension (blood pressure response to renal artery repair) as the reference standard, the accuracy of the scan improves, with the negative predictive value of a low probability scan for renovascular hypertension increasing to 97%. Scintigraphic results were also positively correlated with renal vein renin values in a statistically significant fashion (two-tailed Fisher exact test statistic = 6.43, P = 0.0219). Captopril-enhanced 99Tcm-MAG3 renal scintigraphy is a moderately accurate technique for detecting renal artery stenosis. More importantly, our preliminary findings suggest that the scintigraphic technique using 99Tcm-MAG3 appears to predict the blood pressure response to renal artery repair in subjects with suspected renovascular hypertension, thereby separating subjects with haemodynamically insignificant renal artery stenosis from those with renovascular hypertension.

Crossed cerebellar diaschisis associated with balloon test occlusion of the carotid artery.

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomographic (SPECT) brain imaging performed in conjunction with balloon test occlusion of the carotid artery has been used to assess risk of neurologic sequelae that might follow permanent surgical ligation of the artery. The predictive value of cortical hypoperfusion during temporary carotid occlusion for adverse neurologic events has been debated in previous publications. We believe that the risk of an adverse event is greater when a reduction in cortical perfusion during balloon test occlusion is associated with crossed cerebellar diaschisis (CCD). To test our hypothesis we evaluated the results of 27 99Tcm-HMPAO SPECT brain studies obtained in association with balloon test occlusions of the carotid artery. In each case we correlated clinical outcome with the presence or absence of regional decreases in cerebral perfusion and CCD. All of the 27 patients were free of neurologic symptoms during the balloon test occlusion. Seventeen of the 27 scintigraphic studies were felt to be abnormal, showing cortical perfusion defects all on the side of the occlusion. Among these 17 patients, five demonstrated CCD. Four of these five CCD patients showed evidence for cerebral cortical ischaemia on the side of the temporary carotid occlusion either shortly after the procedure or following carotid artery sacrifice. Of the remaining 12 patients with regionally reduced cerebral perfusion and no CCD, none showed evidence for cortical ischaemia in association with balloon test occlusion, and five of these 12 patients had carotid ligation without subsequent neurologic sequelae.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of infection in ununited fractures. Combined imaging with indium-111-labeled leukocytes and technetium-99m methylene diphosphonate.

The results of combined scintigraphy in which indium-111-labeled leukocytes and technetium-99m methylene diphosphonate were used were compared with the results of cultures of open bone at 102 sites of delayed union or non-union, to determine the effectiveness of this combination as a preoperative indicator of osteomyelitis. There were twenty-five true-positive, fifty-nine true-negative, eleven false-positive, four false-negative, and three indeterminate interpretations, yielding, for the diagnosis of osteomyelitis, a sensitivity of 86 per cent, a specificity of 84 per cent, an accuracy of 82 per cent, a positive predictive value of 69 per cent, and a negative predictive value of 94 per cent. There were few false-negative scans; false-positive results were most likely at a metaphyseal site adjacent to a joint in which there was post-traumatic arthropathy, at the site of a failed arthrodesis, and at the site of an unstable delayed union or non-union.

A scintigraphic sign for detection of right-to-left shunts.

We evaluated the usefulness of a new scintigraphic sign, a quantum mottling pattern, in diagnosing right-to-left shunt using 99mTc-MAA particles. The quantum mottling pattern is characterized by random distribution of discrete clumps of radioactivity that are more intense than the general body background. Forty-nine 99mTc-MAA scintigrams were analyzed retrospectively for presence of a quantum mottling pattern in extrapulmonary soft tissues and brain. This distinctive pattern was observed in every patient (18/18) in whom a right-to-left shunt was confirmed by nonscintigraphic means and was noted only in one patient in whom independent proof of a right-to-left shunt was not available. In contrast, application of conventional criteria yielded a true-positive interpretation for 15/18 patients with right-to-left shunts and a false-positive interpretation for another four patients. Presence of a quantum mottling pattern on 99mTc-MAA images appears to be a reliable aid for detecting a right-to-left shunt. Use of this sign is likely to improve accuracy of the scintigraphic test in patients with small shunts.

Hepatobiliary excretion of MAG3. Simulation of a urinary leak.

A Tc-99m MAG3 renal scintigram was performed on a patient with severe renal insufficiency and bilateral ureteral stents. The Tc-99m MAG3 study displayed typical findings for renal insufficiency but also suggested the presence of lower tract obstruction. Moreover, the delayed posterior and posterior oblique views of the abdomen revealed an extrarenal collection of tracer suggestive of a urinary leak. With the help of additional views, this extrarenal activity was proven to be tracer in the bowel and biliary system. Biliary excretion of Tc-99m MAG3 can be prominent in patients with renal insufficiency and could lead to an erroneous diagnosis of urinary leak. Finally, scintigraphic diagnosis of lower tract obstruction may be difficult in patients with renal insufficiency, but some helpful signs may lead to the correct diagnosis.

An emission-based technique for obtaining attenuation correction data for myocardial SPECT studies.

In this paper, a technique is described for obtaining the information needed to perform attenuation correction in the thorax entirely from an emission study. This technique is based on the observation that the variation in soft tissue and lung attenuation coefficients is small among individuals. Thus only the outer contours of the body and lungs need be determined for obtaining the attenuation map. The contours are determined by using 99Tcm-macroaggregated albumin (MAA) to locate the lungs and an external source wrapped about the chest to locate the body boundary. Simulation studies were performed to investigate how errors in the presumed tissue attenuation coefficients affect the accuracy of the correction. Body and lung attenuation coefficients were varied from 20% less to 20% more than the coefficients used in the corrections. Over this range, there was less than a 15% alteration in the relative distribution of counts in the left ventricle. To test clinical feasibility, seven patients referred for clinical myocardial perfusion studies were scanned before and after the placement of the body source and the administration of 99Tcm-MAA. Reconstructed images from these studies showed clear demarcation of all body and lung boundaries. The presence of 99Tcm-MAA in the lungs had no significant effect on the clinical interpretation of the single photon emission computed tomographic (SPECT) studies. It is concluded that this technique is feasible for clinical application and that it offers important advantages over other current methods.

Dual isotope brain SPECT imaging for monitoring cognitive activation: physical considerations.

The physical considerations of using dual isotope brain SPECT imaging to monitor blood flow changes during cognitive activation studies were investigated. These factors included field uniformity, spatial resolution and crosstalk. Serial dual isotope single photon emission computed tomographic (SPECT) studies of a test tube phantom and an anthropomorphic brain phantom filled with 99Tcm and 123I were made over a 10 h period. The reconstructed counts in the 99Tcm and 123I windows were corrected for crosstalk and were plotted as a function of time. The plotted data from each window decreased over time with a half-life characteristic of each radionuclide. The relative difference between true 123I and 99Tcm region counts has to be of the order of 10% to be statistically significant at the P < 0.05 level.

Dual isotope brain SPECT imaging for monitoring cognitive activation: initial studies in humans.

A dual isotope, single photon emission tomography (SPECT) technique using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 123I-iodoamphetamine (IMP) was investigated to determine its suitability for assessing regional cerebral blood flow (rCBF) changes resulting from cognitive activation. The similarity of the 123I-IMP and 99Tcm-HMPAO distributions under the same physiological conditions was first investigated by administering the two agents to human subjects (n = 8) either simultaneously or at different times but during the performance of the same task. Normalized ratio images generated from the 99Tcm and 123I data showed that the two tracers distributed similarly in the left and right cerebral hemispheres when administered under similar physiological conditions. There was, however, a significant anterior/posterior gradient that appears to be the result of partial volume effects due to small differences in spatial resolution of the two agents. In two subjects, 99Tcm-HMPAO was administered during a resting period with eyes-closed and 123I-IMP was injected later during visual checkerboard stimulation. Ratio images showed a localized increase in the occipital lobes during the visual stimulation consistent with the expected increase in rCBF. The dual isotope strategy appears promising for study of changes in rCBF due to cognitive activation.

Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.

The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.

Immunological evaluation of pediatric cancer patients receiving recombinant interleukin-2 in a phase I trial.

Immunological evaluations were performed on 14 pediatric cancer patients who received human recombinant interleukin-2 (rIL-2) as a bolus intravenous infusion every 8 h for 5 consecutive days in a phase I trial. Three-to-four patients were treated at dose levels of 10, 30, 60, and 100 x 10(3) Cetus U/kg. Six of the patients had stage D neuroblastoma; the remainder had other solid tumors or leukemias. Infusion of rIL-2 was associated with a rapid margination of IL-2-responsive cells followed by demargination and heightened proliferative and cytotoxic activity after therapy was completed. The predominant phenotypic change in circulating peripheral blood mononuclear cells (PBMC) was an increase in CD2 expression by CD56+ natural killer (NK) cells. Appearance of CD2+ CD56+ cells in the circulation correlated with increased lymphokine-activated killer (LAK) cell activity as defined by the ability to kill NK-resistant Daudi tumor cells in vitro. Sustained LAK activity appeared to be dependent on the bioavailability of rIL-2 in vivo as well as in vitro. After rIL-2 therapy, PBMC that were highly responsive to rIL-2 (activated and "poised" LAK cells) persisted for at least 72 h. In the patients tested, increased lysis of autologous and/or allogeneic, histologically similar tumor cell lines was also observed after therapy. The immunoenhancing effects of rIL-2 occurred even at the lower doses used in this study. However, an objective tumor response was not observed in any of the patients.