Exercise increases the lung clearance of inhaled technetium-99m DTPA

The regional lung clearance of a deposited aerosol of [99mTc] diethylenetriaminepentaacetic acid was successively computed at rest and at exercise in seven nonsmoking volunteers in upright posture. The subjects were seated on a bicycle with their backs against a gamma camera. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise this regional gradient was enhanced by a large and significant increase of the apical clearances (3.40 +/- 0.63% min-1 s.d. compared with 1.82 +/- 0.75% min-1 s.d. at rest, n = 7, p less than 0.01). By contrast the changes of the basal clearances were slight and unsignificant (1.46 +/- 0.71% min-1 s.d. compared with 1.40 +/- 0.82% min-1 s.d.). This increase of the apical lung clearance could be attributed primarily to the increase of apical blood flow induced by exercise and to the subsequent increase of the permeability surface area product.     

The rapid reversibility of effects of changing lung volume on the clearance rate of inhaled 99Tcm-DTPA in man

Five normal non-smoking subjects inhaled an aerosol of 99Tcm-DTPA in saline with a mass median aerodynamic diameter of 0.6 micron. The rate of clearance (k) of the inhaled 99Tcm-DTPA from lung to blood was measured using a gamma scintillation camera with computer data acquisition. During a single clearance study the subjects voluntarily breathed close to total lung capacity (TLC) and close to residual volume (RV). They breathed at one volume for 5 min, then at the opposite volume for 5 min and finally reverted to the original volume for 5 min with a 1 min pause between each manoeuvre. The order in which each subject performed these breathing patterns was randomized. Tidal volume, respiratory frequency and end expired volume were measured with a water spirometer. When they breathed close to TLC the rate of clearance increased (k = 4.62 +/- 1.03%/min) compared with breathing close to RV (k = 1.96 +/- 0.5%/min). This effect of changing volume was immediately reversible after adopting each new lung volume. There were no significant changes in tidal volume or respiratory frequency between each 5 min period. There was no significant difference between the clearance increased (k = 4.62 +/- 1.03%/min) compared with breathing close to RV (k = 1.96 +/- 0.5%/min). This effect of changing volume was immediately reversible after adopting immediate and reversible.     

123I-IMP clearance of the lung with diffuse lung disease

N-isopropyl-I-123-p-iodoamphetamine (123I-IMP) is taken up by the capillary endothelial cells during the first pulmonary pass and is released from the lung. To evaluate the effect of the 123I-IMP retention on diffuse lung disease, we studied prolonged 123I-IMP clearance from lung in 5 non-smoking control volunteers and 15 patients with various diffuse lung diseases. The time-activity curve for 60 min after the injection of 111 MBq of 123I-IMP was described as follows: C(t) = A1e-k1t + A2e-k1t (A1, A2: intercepts; K1, K2: slopes of the exponential components). 123I-IMP clearance was delayed in the patient group and K2 was significantly lower. There was a significant correlation between K2 and Ga-computer activity index on the 67Ga scintigraphy in the patient group. K2 was also correlated with %Dlco on the pulmonary function test. Our study suggests that the delayed clearance and retention of 123I-IMP in the diseased lung are influenced by the pathological activity in the lung lesion.     

Recirculation of inhaled xenon does not alter lung CT density

RATIONALE AND OBJECTIVES: Xenon-enhanced computed tomography (Xe-CT) measures regional ventilation from changes in lung parenchymal CT density during the multibreath washin/washout of inhaled Xe gas. Because Xe is moderately soluble, vascular uptake and redistribution has been proposed as a confounding phenomenon. We propose that the redistribution of Xe via the circulation is negligible, and correction is unwarranted. MATERIALS AND METHODS: Unilateral ventilation with 60% Xe was performed in intubated canines. Whole-lung CT images were obtained at baseline and after 1 and 5 minutes of unilateral Xe ventilation. Comparisons between blocked (B) and Xe ventilated (V) whole lung densities were made. Density of paraspinous muscle and blood (aorta, inferior vena cava) were also compared. RESULTS: The density of lung tissue in the V lungs increased significantly compared to B lungs after 1 minute (B -688.5 +/- 54.3 Hounsfield units [HU] vs. V -535.4 +/- 55.6 HU, P < .05) and 5 minutes (B -689.1 +/- 52.2 HU vs. V -492.9 +/- 89.1 HU, P < .05) of Xe ventilation. The density in the blocked lungs did not significantly change after either 1 or 5 minutes of ventilation with Xe. Although density tended to increase with time in the blood and muscle, the change only reached significance in muscle at 5 minutes. CONCLUSIONS: Five minutes of ventilation with a high concentration of Xe does not cause measurable density changes in the contralateral, unventilated lung. Xe accumulation in muscle tissue limits redistribution. Correction of Xe-CT time series density data may be unnecessary.     

吸入氡致大鼠肺蛋白质组表达变化的分析

目的 从蛋白质组学角度分析氡染毒后大鼠肺组织蛋白质表达谱的变化。方法 雄性Wistar大鼠氡吸入染毒累积剂量分别达100、200、400工作水平月(WLM)后,取大鼠肺组织,裂解提取其总蛋白;双向电泳(2-DE)分离总蛋白,ImageMaster 2D Platinum软件分析差异表达蛋白,切取差异蛋白点,胶内酶解并进行质谱(MALDI-TOF-MS)鉴定。结果 正常对照组和氡染毒组大鼠肺组织的2-DE图谱有明显差异,差异表达点中与氡染毒呈剂量变化关系的点有14个表达上调,9个表达下调,质谱鉴定出其中的15个差异蛋白点。结论 氡染毒组大鼠肺组织的蛋白表达谱发生了一定的差异性,氡吸入致靶器官肺损伤可能与多种蛋白相关。     

Visualizing water clearance in the lung with MRI

Current indirect measurements of alveolar fluid clearance (AFC) suggest that the rate of fluid clearance correlates with morbidity and mortality in patients with pulmonary edema. In a traditional AFC-measurement, fluid laced with a tracer macromolecule is instilled into the lung and thereafter repeated samples of the instilled fluid are extracted from the lung's fluid-filled airspaces. The change in concentration of the tracer molecule indicates the AFC-rate. In this work, a new MRI technique was developed to image lung water clearance by adding Gadolinium-DTPA to the instilled fluid. As fluid is absorbed by the animal, the concentration of gadolinium will increase, reducing the T(1) relaxation time. By repeatedly measuring the T(1) relaxation time, the AFC can be tracked over time with high spatial resolution. The new technique was tested both in phantoms and 10 Yorkshire piglets.     

Methodologic considerations in mucociliary clearance and lung epithelial absorption measurements

Measurements of mucociliary clearance and lung epithelial permeability are relatively simple to perform, with minimum discomfort to the subjects. Awareness of the factors influencing the outcome of these procedures will help to avoid errors and yield useful information about these two clearance mechanisms from both a physiological and a pathological point of view.

     

Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung

Iodine 123 N-isopropyl p-iodoamphetamine (¹²³I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied ¹²³I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of ¹²³I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 × 64 matrix were obtained. The ¹²³I-IMP clearance curve was described as follows: C (t) = A ₁e^–k ₁ t+ A ₂e^–k ₂ t (A1, A ₂: intercepts, and k ₁, k ₂: slopes of the exponential components). ¹²³I-IMP clearance was delayed in smokers, and k ₂ was smaller in smokers. Also, a correlation between k ₁, k ₂, and the number of cigarettes smoked per day was found (r = –0.65, r = –0.74, respectively, P<0.01). In conclusion, this study suggests that the delayed clearance and retention of ¹²³I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.Offprint requests to: K. Kato     

Evaluation of lung epithelial permeability

During the last few years a number of factors affecting the measurement of the rate of absorption of ^99mTc-DTPA across the alveolar-capillary membrane have been identified. These have helped to provide insights into the significance of lung epithelial permeability (LEP) measurements and their potential limitations. Pulmonary absorption of ^99mTc-DTPA has been studied in a variety of clinical conditions and the results are discussed.

     

Effects of cigarette smoking on I-123 IMP clearance from the lung

N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the cigarette smoking on the uptake of IMP by the lung, we studied I-123 IMP clearance from the lung of 14 volunteers; 5 non-smokers and 9 smokers. After the injection of 111 MBq (3 mCi) of I-123 IMP into the medial cubital vein, the time-activity curve for 60 minutes and the regional activity using 1 frame per minute and a 64 x 64 matrix was obtained. I-123 IMP clearance curve was described as follows: C(t) = A1e-k1t + A2e-k2t (A1, A2: intercepts, and k1, k2: slopes of the exponential components). I-123 IMP clearance was delayed in smokers, and k2 was smaller in smokers. Also a significant correlations between k1, k2, and the number of cigarettes smoked per day were found. In conclusion, this study suggests that the delayed clearance and retention of I-123 IMP in the lung indicate the lung metabolic disorders due to cigarette smoking.     

Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung.

Iodine 123 N-isopropyl-p-iodoamphetamine (123I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied 123I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of 123I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 x 64 matrix were obtained. The 123I-IMP clearance curve was described as follows: C(t) = A1e-k1t + A2e-k2t (A1, A2: intercepts, and k1, k2: slopes of the exponential components). 123I-IMP clearance was delayed in smokers, and k2 was smaller in smokers. Also, a correlation between k1, k2, and the number of cigarettes smoked per day was found (r = -0.65, r = -0.74, respectively, P less than 0.01). In conclusion, this study suggests that the delayed clearance and retention of 123I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.     

Early retardation of 99mTc-DTPA radioaerosol transalveolar clearance in irradiated canine lung.

The alteration of 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) transalveolar clearance in an initial phase of radiation lung injury was experimentally investigated. METHODS: Fourteen dogs were irradiated to the hemithorax with a single dose of 20 Gy. A DTPA radioaerosol study was performed before irradiation and on day 12 after irradiation. On day 14, the DTPA study was repeated again, with seven animals undergoing the study after inhalation of an aerosolized synthetic surfactant. The penetration index (P.I.) and clearance half-time (T(1/2)) of DTPA were measured in each lung. To evaluate the changes in lung surfactant after irradiation, alveolar lipids were stained in the resected lungs (n = 14), and the amounts of alveolar surfactant phospholipid and protein were measured by a bronchoalveolar lavage study in another six irradiated dogs. RESULTS: In all of the 14 irradiated animals, DTPA radioaerosol distributed uniformly throughout the lungs without significant changes in P.I. The T(1/2) values in irradiated lungs were significantly prolonged compared with the matched baseline values and those in nonirradiated lungs (P < 0.05 and 0.001, respectively). The aerosolized synthetic surfactant retarded the DTPA clearance both in the irradiated and in the nonirradiated lungs (P < 0.001) without significant changes in P.I. The histologic and bronchoalveolar lavage studies revealed an increase of alveolar surfactant materials in the irradiated lungs without substantial histologic changes in the alveolar structures. CONCLUSION: DTPA transalveolar clearance was retarded soon after irradiation. Increased alveolar surfactant may be partly responsible for this retarded DTPA clearance because the aerosolized synthetic surfactant also prolonged the clearance in nonirradiated lungs. A DTPA clearance test is sensitive for the early detection of radiation lung injury and seems helpful for clarifying the association of epithelial integrity changes and lung surfactant in radiation lung injury.     

Tagging of iron oxide particles with 99mTc for use in the study of deposition and clearance of inhaled particles.

This paper describes a method of tagging iron oxide aerosol particles with 99mTc. The tagging is achieved by reducing the heptavalent pertechnetate form to its reduced state using stannous chloride in a nitrogen atmosphere. Tests by ultracentrifugation and paper chromatography shown that the tagging is virtually complete. Separation of the tag from the particles in sputum is shown to be minimal. Monodisperse aerosols of the tagged particles are produced with a spinning-disk atomizer. (Deposition and clearance of the particles in the airways and lungs is easily followed by scintigraphy.) Factors affecting attachment and separation of the tag are discussed.     

The influence of changing dose rate patterns from inhaled beta-gamma emitting radionuclide on lung cancer

Purpose: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (⁹⁰Sr), cerium-144 (¹⁴⁴Ce), yttrium-91 (⁹¹Y), or yttrium-90 (⁹⁰Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed.

Materials and methods: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DR_ef).

Results: Dogs exposed to DRef (1–100?Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1–10?Gy/day) died of lung cancer. As DR_ef decreased further (<0.1?Gy/day ⁹⁰Sr, <0.5?Gy/day ¹⁴⁴Ce, <0.9?Gy/day ⁹¹Y, <8?Gy/day ⁹⁰Y), survival and lung cancer frequency were not significantly different from control dogs.

Conclusion: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.     

Evaluation of the renal clearance of technetium-99m PAHIDA in dogs

The renal clearance of the technetium-99m complex of para[(biscarboxylmethyl)-aminomethylcarboxyamino]hippuric acid ([99mTc]PAHIDA), has been previously studied in rodents and falls between that of [99mTc]DTPA (diethylenetriaminepentaacetic acid) and iodine-131 (131I) orthoiodohippuran (OIH). To investigate the effect of species variation, the plasma clearance of [99mTc]PAHIDA was investigated in dogs. The plasma disappearance of the renal agent approached that of [99mTc]DTPA and was significantly less than that of OIH. Despite the structural similarities of the PAHIDA ligand and aminohippurate, the [99mTc]PAHIDA complex undergoes little, if any, tubular secretion in the canine kidney.     

Temporal changes in accumulation of N-isopropyl-p-iodoamphetamine in human brain: relation to lung clearance

Temporal changes in brain uptake of 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) were studied by means of a multi-detector single photon emission computed tomography (SPECT) scanner. Serial dynamic SPECT scan was performed for 50 min following an i.v. bolus injection of IMP in 30 patients with various neurologic diseases. In 18 of them the radioactivity in the lung was also recorded by a single probe detector during the serial dynamic SPECT scan. Brain activity showed a gradual increase after the injection of IMP, reaching 63 +/- 7% of the maximum activity at 5 min and 90 +/- 5% at 20 min. The lung clearance showed a large variation among the individual cases; 29 to 72% (52 +/- 11%) of the initial peak activity at 20 min and 22 to 57% (41 +/- 9%) at 50 min after the injection. A significant positive correlation was observed between the clearance half-time in the lung and the time to reach 90% of the maximum activity in the brain (r = 0.86, p less than 0.001). These results suggested that brain uptake of IMP is influenced by the lung clearance and the optimum time to start SPECT data acquisition using a conventional rotating gamma camera system is 20 min after the injection.     

Production of 99mTc-labeled iron oxide aerosols for human lung deposition and clearance studies

Radiolabeled aerosols used in human lung deposition and clearance studies require nontoxic particles firmly tagged with low dose isotopes. An iron oxide sol was prepared by deionizing a ferric nitrate solution. A rapid and efficient method of labeling with ^99mTc was developed. Initial binding approached 100% and product yields exceeded 90% for iron oxide concentrations greater than 1 mg ml⁻¹. ^99mTc leakage from both iron oxide aqueous colloids and monodisperse particles was assayed by pressure dialysis. Over 24 h, aqueous colloidal leaching in saline and simulated lung fluid was less than 2%, whereas particle leaching was 15.4% and 6.4%, respectively.     

Urine excretion of inhaled technetium-99m-DTPA: an alternative method to assess lung epithelial transport

Technetium-99m DTPA clearance (99mTc-DTPA) clearance measured by a gamma camera or a scintillation probe not only reflects epithelial transport, but is also influenced by an unknown amount of mucociliary clearance depending on particle size and aerosol deposition. This is confirmed by factor analysis of dynamic inhalation studies. Assessment of epithelial absorption by urinary excretion of inhaled 99mTc-DTPA is largely independent of aerosol lung deposition. Twenty-four-hour excretion reflects the amount of aerosol cleared by absorption, while two-hour excretion is a quantitative measure of the aerosol absorption rate from the epithelium into blood. Urinary 99mTc-DTPA excretion of two aerosols with different particle size correlated significantly (p less than 0.001) with analysis of lung clearance curves. A very similar regression in the form of a cumulative exponential function was found with both aerosols. Two-hour urine values of nonsmokers differed significantly from those of smokers or patients with active interstitial or infectious lung disease. This alternative procedure is suited as a bedside test and holds promise for patient monitoring and follow-up.     

Evaluation of plasma clearance by synthesis of continuous infusion: principles and use

There is a technique of engineering analysis which can be described as "impulse synthesis" which uses the observational data of a system's response to a single sharp blow in order to predict its response to a steady force. This same technique has been applied to the calculation of in situ drug levels and for calculating plasma clearance values. The purpose of this paper is to elucidate the principles of this calculation technique and to critically assess its application to plasma clearance studies. We begin by tracing the history of the measurement of renal clearance of plasma. We then proceed to exposit the relevant principles of the synthesis technique. Finally, we report the results of our application of this technique to the analysis of simulated data in a manner intended to be of use to clinicians who might wish to consider employing the technique.