Search

Purpose: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy., Materials and Methods: After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection., Results: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans., Conclusion: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.

Unlabelled: PET is a technique with a strong potential for use in drug evaluation and development. In particular, the distribution and pharmacokinetics of locally administered drugs may be advantageously explored noninvasively using labeled compounds. This pilot study was performed to demonstrate the effectiveness of PET for drug development and to determine the human biodistribution and kinetics of triamcinolone acetonide, labeled with 11C, formulated and nasally administered as Nasacort AQ nasal inhalant., Methods: Carbon-11-labeled triamcinolone acetonide was formulated as the commercial product, and PET scans of the heads of four volunteers were performed in a vertical orientation. Region-of-interest analysis with MRI coregistration was used to analyze the distribution and kinetics in nasal tissues., Results: Deposition of the majority of the dose on target tissues was immediate. Penetration into sinuses was observed. There was moderate redistribution and slow migration of the drug through nasal passages to the throat. Significant amounts of the drug remained in target regions for several hours., Conclusion: PET is an effective means to determine local drug distribution and kinetics.

Background: The difficulties involved in the timely and accurate diagnosis of pancreatic disease are well known. The usual imaging modalities usually identify abnormalities but may not always differentiate malignancy from other condition such as scar tissue or chronic inflammation. The purpose of our study was to determine if fluorodeoxyglucose positron emission tomography (FDG PET) can accurately diagnose pancreatic disease., Methods: The records of 15 patients presenting with pancreatic disease were retrospectively reviewed. The diagnosis suspected by imaging modalities was compared with the final tissue diagnosis. Two patients were excluded because no tissue was obtained., Results: Adenocarcinoma was diagnosed in 9 patients. A mass consistent with this diagnosis was seen in 8 of 9, 6 of 9, 6 of 8, and 5 of 5 patients by PET, computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS), respectively. Chronic pancreatitis (CP) was diagnosed in 2 patients. The unique appearance on FDG PET made the diagnosis in both these patients. Both patients with CP were thought to have a malignancy by CT and EUS and 1 of 2 by ERCP. Neuroendocrine tumors were diagnosed in 2 other patients. One of 2 was seen by FDG PET and both by CT., Conclusions: FDG PET can accurately differentiate a pancreatic adenocarcinoma from chronic pancreatitis in a patient with a suspicious pancreatic mass. Thus, FDG PET may help in establishing a diagnosis and subsequently managing a patient with pancreatic disease.

Evaluation of the retroperitoneum is important to assess the extent of retroperitoneal malignancies and because the retroperitoneum is a route of nodal spread for other malignancies. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) allows detection of small malignant nodes not identified or not meeting size criteria for malignancy with computed tomography (CT) and tumor recurrences in surgical beds that are otherwise difficult to assess. However, evaluation of retroperitoneal malignancies or adenopathy with FDG PET can be complicated by urinary and colonic activity or anatomic variants. Urinary artifacts are avoided with intravenous hydration, administration of furosemide, and catheterization and retrograde filling of the bladder with saline solution. Colonic artifacts are avoided by cleansing the bowel with an isosmotic solution. FDG PET is useful in assessing the retroperitoneum for adenopathy in malignancies such as testicular cancer; lymphoma; and rectal ovarian, or cervical cancer that spread along retroperitoneal lymphatics. FDG PET is especially useful for detection of malignant nodes that do not meet size criteria at CT or when lack of retroperitoneal fat makes it difficult to identify retroperitoneal nodes with CT. FDG PET has an important role in evaluation of postoperative beds, where CT has limited useful because of altered anatomy, surgical clip artifacts, and scar issue.

Background: Positron emission tomography (PET) with fluorine-18 labeled deoxyglucose (FDG) can detect tumor recurrences in surgical patients that are otherwise difficult to assess by CT, as well as distant metastases and small malignant nodes that are not identified by other imaging modalities. However, the evaluation of such malignancy is complicated by urinary and colonic concentrations of FDG. Methods and examples of the elimination of artifactual accumulation of FDG in PET imaging of the abdomen and pelvis are presented., Methods: Elimination of artifactual accumulation requires patient preparation that begins with cleansing of the colon using an isosmotic solution taken the evening prior to examination. Approximately 500 MBq of F-18 FDG is intravenously administered upon arrival at the PET facility and then the patient is hydrated. After administration of furosemide, a Foley catheter with a drainage bag is placed and the patient is then scanned. Just prior to scanning over the pelvis, normal saline is delivered retrogradely into the urinary bladder. At the end of scanning, the patient voids and repeated pelvic images are obtained., Results: These routines yield a clean scanning field. Lesions that will generally be missed because they are obscured by FDG accumulations along the colon or in the kidneys, ureters, or bladder are better visualized and identified with greater confidence. Artifacts that lead to misinterpretation also are reduced., Conclusion: Elimination of artifactual accumulation of FDG in the colon and urinary system is essential if primary cancer, associated adenopathy, or subtle recurrences are to be evaluated in FDG PET imaging of the abdomen and pelvis.

Unlabelled: PET tumor imaging of the abdomen and pelvis is prone to artifacts due to urinary tract activity. A new technique has been developed to reduce such artifacts and enhance study interpretation., Methods: Thirty minutes after the injection of 18F-FDG, 500 cc 0.45% NaCl were administered intravenously over 30 min and a Foley catheter was placed in the bladder. At the start of imaging (60 min post-injection), furosemide was given (0.3 mg/kg). Prior to imaging the pelvis, the urinary catheter was clamped and saline was introduced retrograde into the bladder until full., Results: This technique has been used successfully in more than 130 patients, resulting in a marked improvement in study quality and tumor detection., Conclusion: Hydration and administration of furosemide, along with placement of a Foley catheter in the bladder, have proven effective in eliminating image artifacts originating from the kidneys, ureters and bladder. Backfilling the bladder also provides a well-defined anatomic landmark for study interpretation.

Unlabelled: The goal of this study was to use PET and 11C-N-methylspiperone (11C-NMSP) to measure the difference in relative occupancy of serotonin (5-hydroxytryptamine-2 or 5-HT2A) and dopamine-2 (D2) neuroreceptors in subjects being treated with typical or atypical antipsychotic drugs., Methods: We used PET and single-dose 11C-NMSP to measure receptor indices and relative receptor occupancy of 5-HT2A receptors in frontal cortex and D2 receptors in basal ganglia in five subjects who were neuroleptic free, five subjects who were being treated with typical antipsychotic drugs and five subjects who were being treated with clozapine, an atypical antipsychotic drug., Results: Among the three groups, there were significant differences in 5-HT2A indices, D2 indices and the ratio of 5-HT2A to D2 indices. With no overlap, the 5-HT2A index separated all subjects who received clozapine and the D2 index separated the remaining two groups., Conclusion: Typical antipsychotic and atypical antipsychotic subjects do have differing patterns of 5-HT2A and D2 relative receptor occupancy when measured with a single PET scan, single 11C-NMSP radiotracer dose and no separately injected "cold" pharmaceutical.

Unlabelled: Carazolol is a promising high-affinity beta-adrenergic receptor ligand for the noninvasive determination of beta receptor status using PET. Earlier investigations demonstrated specific receptor binding of carazolol in mice. These PET studies with S(-)-[2"-11C]carazolol in pigs were performed to explore the utility of the tracer for PET receptor studies., Methods: Tracer uptake in the heart and lung was measured by PET as a function of time. Receptors were blocked with propranolol and different doses of ICI 118,551 to estimate specific binding. Fluorine-18-1"-Fluorocarazolol and the less active R-enantiomer of [11C]-carazolol were also studied., Results: Specific receptor binding was 75% of the total uptake in the heart, preventable and displaceable by propranolol. Dose-dependent competition showed that carazolol binds in vivo to beta 1 and to beta 2 subtypes. Uptake of the labeled R(+) enantiomer of carazolol was not receptor-specific., Conclusions: Carazolol labeled with 11C or 18F is a strong candidate for use in receptor estimation with PET. The in vivo observations were consistent with its known high affinity and slow receptor dissociation rate. Its high specific receptor uptake and low metabolism allow existing kinetic models to be applied for receptor measurements. The 11C label is convenient for repeated administrations, though 18F allowed the long observation periods necessary for measurement of the receptor dissociation rate. If needed, nonspecific uptake can be estimated without pharmacologic intervention by using the labeled R enantiomer.

Study Objectives: The mechanism by which the fluorinated quinolones produce central nervous system effects is unknown. Using positron emission tomography (PET), we evaluated the effects of two quinolones on brain blood flow as well as on oxygen and glucose metabolism. These determinations were done in conjunction with ophthalmologic and neuro-ophthalmologic testing., Design: Randomized, double-blind, placebo-controlled, 7-day course of ciprofloxacin 750 mg (C750) or 500 mg (C500) every 12 hours, or nalidixic acid (NA) 1 g every 6 hours., Population: Twenty-four healthy male volunteers, six in each treatment arm., Results: [table: see text], Conclusions: Compared with baseline values, NA significantly reduced brain glucose uptake, whereas C500, C750, and placebo produced no detectable effect. No compound significantly altered brain blood flow or oxygen metabolism compared with baseline or other treatments. No significant effect on electroretinographic, electro-oculographic, or other neuro-ophthalmologic tests was observed.

Despite its potential to cause myocardial damage, high-dose CY in doses up to 200 mg/kg is an integral part of preparative regimens for BMT. Conventional tests, such as an electrocardiogram or echocardiogram, have lacked sensitivity in prediction of cardiotoxicity in this patient population. We prospectively compared serial electrocardiograms and positron emission tomography scans before and after CY administration to investigate the possible changes in 13N-ammonia perfusion and 18F-2-deoxyglucose metabolism after CY administration in 12 consecutive patients undergoing BMT. Neither global nor regional changes in myocardial N-13 ammonia and 18-fluorodeoxyglucose were significant when compared with baseline studies and control studies (p < 0.05). In a single patient, however, a substantial increase in 13N-ammonia perfusion was seen in the inferior region simultaneously with electrocardiographic T wave inversions in the inferior leads. These changes may be due to alterations in myocardial blood flow or membrane permeability. PET scanning may be a useful adjunct in evaluating CY cardiotoxicity, although further investigations are needed to elucidate its role in clinical practice.

A noninvasive monitor has been developed for monitoring arterial radioactivity in quantitative PET studies of blood flow. The significance of this probe is that quantitative blood flow studies can be performed without the use of arterial catheterization. The method employed is based on the flux of photons emanating from the superior lobe of the right lung following an intravenous bolus of H2(15)O. Calibration of the monitor is obtained by measuring the relationship between lung monitor counts and arterial radioactivity after arterial and venous radioactivity levels have equilibrated following inhalation of C15O. To determine the accuracy of the lung probe as a measure of arterial radioactivity, 44 brain blood flow determinations were made in 11 volunteers using arterial radioactivity measures based both on the lung probe and continuous sampling from a radial artery. Repeated measures analysis of variance found no differences between invasive and noninvasive estimates of blood flow. These results suggest that the lung monitor enables quantitation of cerebral blood flow yet avoids the trauma of an arterial puncture.

The basics of positron emission tomography (PET) are presented, including the physics, instrumentation, and radiopharmaceuticals involved; the clinical and research applications; and the cost. In PET, organic molecules labeled with positron-emitting radionuclides are injected or inhaled, and the high-energy photons produced by annihilation events are detected by paired, integrated crystal detectors. A computer uses the lines of origin of these photons to reconstruct a three-dimensional map of a functioning organ system. The positron-emitting radionuclides most often used are carbon 11, oxygen 15, nitrogen 13, fluorine 18, and rubidium 82. PET imaging centers usually consist of a cyclotron facility, a radiochemistry facility, a PET scanner, and computers for image reconstruction. Radiopharmaceuticals used in PET may be divided into blood flow-imaging agents, metabolic imaging agents, and drug receptor-imaging agents. Although PET is still primarily a research tool, it has shown diagnostic potential in neurology, cardiology, and oncology. It has also shown promise as a tool for pharmacologic assessment, as in studies of the effects of the fluorinated quinolones on cerebral blood flow and glucose metabolism. PET may become important in drug development because it yields specific information relatively noninvasively. A single study carries an average break-even price tag of $1500-$2000; rigorous cost-benefit analyses should be conducted before society is asked to subsidize such costs. Positron emission tomography is a frontier technology for which valuable clinical applications are being discovered. Pharmacists can contribute enormously to PET applications and at the same time establish a unique subspecialty for the profession.

Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

Twenty-five patients with mass lesions involving the musculoskeletal system were studied with positron emission tomography (PET) in order to determine if a relationship exists between histologic grade and tumor uptake of [fluorine-18]2-deoxy-2-fluoro-D-glucose (FDG). There were 6 benign lesions and 19 malignant lesions of various grades. A high correlation (Rho = 0.83) was found between the normalized uptake of tracer and the NCl grade. The high-grade malignancies had significantly greater (p = 0.0091) uptake of FDG than the combination of benign lesions and low-grade malignancies. All lesions with a normalized uptake value of 1.6 or greater were high-grade, while all lesions less than 1.6 represented either benign tumors or low grade malignancies. This strong relationship between FDG uptake and grade among neoplasms from a wide variety of cell types within a single organ system suggests that the technique may be useful in predicting grade even when the cell type is unknown.

Study Objective: To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography., Design: This was a prospective, randomized, double-blind, placebo-controlled study., Patients: The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years., Results: We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours. Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans., Conclusions: We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism. Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects.

Five patients with liposarcomas of the thigh were studied using positron emission tomography (PET) with [18F]2-deoxy-2-fluoroglucose (FDG). There were three low-grade tumors (all National Cancer Institute Grade 1 myxoid liposarcomas) and two high-grade tumors (both pleomorphic liposarcomas, Grades 2 and 3). The low-grade liposarcomas were easily identified with an average dose uptake ratio (DUR) of 1.38 +/- 0.045 (mean +/- SD). The high-grade lesions were more avid for FDG with a mean DUR of 2.45 +/- 0.24. There was a significant difference (p = 0.004) in the DUR for the two groups and the histological grade of malignancy was highly correlated with the DUR for FDG (Rho = 0.89). These findings suggest that FDG-PET may be useful for distinguishing between low-grade and high-grade liposarcomas.

Quantitative measures of physiologic function with PET require continuous monitoring of arterial positron isotope concentration. A device has been developed that automates this process. This device has advantages over manual sampling techniques with syringes since fewer personnel are required, measurements are less error prone, and more continuous measures of arterial positron concentration are available. A constant flow infusion/withdrawal pump withdraws blood from the radial artery through a catheter connected to 0.5 mm inner diameter teflon tubing. This tubing is wrapped around a 50 mm thick by 50 mm diameter NaI(T1) crystal that is interfaced to a photomultiplier tube (PMT) and encased in a cylindrical lead shield. This crystal detects 511 Kev photons that result from positron annihilation. The device sensitivity is greater than 240 (cts/sec)/(microCi/ml) corresponding to a peak activity of approximately 10,000 cts/sec for a 50 mCi bolus injection in an adult. The system dynamic response has been measured and the true arterial input function is recovered by deconvolution. The system has been used clinically for more than 400 human PET studies and has been a reliable continuous monitor of arterial positron concentration.

The basic principles underlying nuclear magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) are explained. Examples of work relating to tumor metabolism are given and some of the important findings of clinical interest are presented. The future prospects of both systems are explored.