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.

A robust edge detection method for gated radionuclide ventriculograms.

UNLABELLED: We present a myocardial edge detection technique that was developed for fast, reproducible measurements of left ventricular ejection fraction in the clinical setting. METHODS: This myocardial edge detection method compares three edge parameters--count amplitude and first and second count derivatives--in three consecutive locations along a radius to a predetermined template of these values. Each of the radii, defined at 10-degree intervals, has different template values that permit accurate edge detection even though adjacent structures, such as the left atrium and the right ventricle, alter edge parameters. The template for edge detection is based on either the average edge parameters determined from manually defined edges in 15 patients (automatic method) or an operator-defined edge in the first frame (semiautomatic method). RESULTS: The edge detection methods were tested in 100 patients, and intraobserver variabilities as well as comparison with clinically obtained ejection fractions were calculated. The standard error of the estimate was less than 3.1% for all observer comparisons. In 15 patients with both high-count (400,000 counts per image) and low count (50,000 counts per image) studies, the mean absolute difference in ejection fraction was 2.6% for intraobserver comparisons. CONCLUSION: A robust myocardial edge detection technique was developed that is applicable for routine clinical use.

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.

Alterations in left ventricular diastolic function with doxorubicin therapy.

To determine whether impaired diastolic function may be an early sign of doxorubicin cardiotoxicity, a retrospective study was performed in 12 patients who had undergone serial radionuclide angiography and were found to have a left ventricular ejection fraction of 55% or more before doxorubicin (Adriamycin) treatment and during follow-up. Average rapid filling velocity and slow filling velocity were both significantly reduced after doxorubicin treatment. Rapid filling velocity decreased from 5.17 +/- 1.52 to 4.18 +/- 0.96 units/s (p less than 0.01), and slow filling velocity decreased from 2.20 +/- 1.32 to 1.42 +/- 0.62 units/s (p less than 0.05). There were no significant changes in filling volume ratio, total diastolic time or diastolic time ratio. Because a change in left ventricular diastolic function can occur before ejection fraction falls to subnormal levels, diastolic function as well as systolic function should be examined for the early detection of doxorubicin cardiotoxicity. The clinical implications of our observations can only be established by a longer-term prospective analysis of left ventricular function in patients receiving doxorubicin therapy.