Noninvasive arterial monitor for quantitative oxygen-15-water blood flow studies.

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.

Specific beta-adrenergic receptor binding of carazolol measured with PET.

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.

Biodistribution and kinetics of nasal carbon-11-triamcinolone acetonide.

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.

Assessment of the effects of ciprofloxacin and nalidixic acid on cerebral blood flow and metabolism in healthy subjects by positron emission tomography.

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.

Comparative assessment of the effect of lomefloxacin, ciprofloxacin, and placebo on cerebral blood flow, and glucose and oxygen metabolism in healthy subjects by positron emission tomography.

The mechanism by which the fluorinated quinolones produce central nervous system (CNS) effects is currently unknown. We measured the effect of lomefloxacin on cerebral blood flow and metabolism using positron emission tomography. Eighteen healthy, nonsmoking volunteers were randomized to receive lomefloxacin 400 mg, ciprofloxacin 750 mg, or placebo given in a single-blind fashion every 12 hours for 72 hours, the time window for maximum lomefloxacin CNS effects. Subjects receiving lomefloxacin had a mean (+/- SEM) cerebral blood flow (CBF) of 46 (2.9) ml/min/100 g, glucose metabolism (FDG) 4.7 (0.4) mg/min/100 g, oxygen metabolism (OM) 3.3 (0.3) ml/min/100 g, and oxygen extraction (%OM) 0.4 (0.04). Posttreatment values were 43 (3.6) ml/min/100 g, 4.2 (0.4) mg/min/100 g, 2.6 (0.3) ml/min/100 g, and 0.4 (0.03), respectively. Values for subjects receiving ciprofloxacin were CBF 44.8 (1.6) ml/min/100 g, FDG 4.9 (0.7) mg/min/100 g, OM 4.1 (0.4) ml/min/100 g, and %OM 0.6 (0.03) at baseline, and 40.3 (3.5), 4.5 (0.6), 3.4 (0.4), and 0.5 (0.09), respectively, after treatment. For placebo-treated subjects, baseline values were CBF 41.4 (1.9) ml/min/100 g, FDG 4.9 (0.5) mg/min/100 g, OM 3.3 (0.4) ml/min/100 g, and %OM 0.5 (0.07), and respective posttreatment values were 42.1 (2.3), 5.0 (0.6), 3.5 (0.3), and 0.5 (0.02). No effect was observed on visual (qualitative), blinded reading of the scans. No significant effect on cerebral blood flow or metabolism was detected. We conclude that short-term administration of lomefloxacin or ciprofloxacin to healthy volunteers does not have a significant effect on cerebral blood flow, or on oxygen or glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Technical improvements in fluorine-18-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.

Elimination of artifactual accumulation of FDG in PET imaging of colorectal cancer.

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.

Continuous arterial positron monitor for quantitation in PET imaging.

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.

Hyperventilation-induced reduction in cerebral blood flow: assessment by positron emission tomography.

The use of positron emission tomography (PET) has been well documented as a relatively noninvasive method of measuring cerebral blood flow (CBF), both globally and regionally. The utility of readily detecting alterations in CBF is apparent, particularly when applied to the evaluation of therapeutic interventions thought to influence CBF. We report the effects of hypocapnia, an experimental condition of known cerebral vasoconstriction, in ten normal volunteers. Subjects had brain blood flow evaluated utilizing H215O as the positron emitter before and after approximately five minutes of hyperventilation. Baseline CBF was measured as a mean +/- SD of 61.2 +/- 16.3 mL/min/100 g of tissue. Mean baseline arterial blood gas values were PaO2 107.4 +/- 14 mm Hg, PaCO2 37.7 +/- 0.89 mm Hg, and pH 7.39 (calculated from mean [H+]). Post hyperventilation, global CBF was measured as 31.1 +/- 10.8 mL/min/100 g. Mean arterial blood gas values were PaO2 141.7 +/- 21 mm Hg, PaCO2 19.7 +/- 5 mm Hg, and pH 7.63 (calculated from mean [H+]). CBF decreased by a mean of 49.5 +/- 11 percent. Data analysis using the Student's t-test showed a significant change over baseline in PaCO2 (p less than 0.001) and CBF (p less than 0.001), in the hyperventilated state. Correlations were noted between the decrease in CBF and change in PaCO2 (r = 0.81) as well as between hyperventilation PaCO2 and the change in CBF (r = 0.97). We conclude that, as measured by PET, CBF decreases significantly during a state of artificial hyperventilation to a degree consistent with results seen using other methods. PET appears to be a valuable tool in the assessment of interventions that could influence CBF.