Computerized tomography versus perfusion lung scanning in canine radiation lung injury.

Computerized tomographic (CT) measurements of lung density were obtained before and serially after thoracic irradiation in dogs to detect the alterations caused by radiation therapy. Fourteen mongrel dogs were given either 2000 cGy (Group A, 10 dogs, right lower zone irradiation), 1000 cGy (Group B, 2 dogs, right lower zone irradiation), or 500 cGy (Group C, 2 dogs, right lung irradiation) in one fraction. Once before and bi-weekly after irradiation, the anesthetized dogs had thoracic CT scans. CT numbers for the irradiated area were compared to their preirradiation control values. Macro-aggregated albumin (MAA) perfusion lung scans were also obtained before and at weekly intervals after irradiation and were evaluated visually and quantitatively for abnormalities. When both these tests were abnormal, or at the end of the scheduled study, the dogs were sacrificed to confirm radiation lung injury histologically. Our results showed that CT numbers (as a measure of tissue density) were higher with higher doses of radiation. Among all the techniques used, only the quantitative assessment of macro-aggregated albumin perfusion scan detected abnormalities in all the dogs given 2000 cGy. Their abnormalities correlated well with the presence of radiation lung damage histologically, however, the applicability of these methods in the detection of early injury has to be further evaluated.

High-frequency oscillatory ventilation increases canine pulmonary epithelial permeability.

To investigate the effect of high-frequency oscillatory ventilation (HFOV) on the pulmonary epithelial permeability, we measured the clearance rate of nebulized sodium pertechnetate (99mTcO4-) and diethylenetriaminepentaacetate (99mTc-DTPA) before and after a 4-h period of mechanical ventilation in anesthetized mongrel dogs. The animals also underwent experiments with 4 h of spontaneous breathing (SB) and intermittent positive-pressure ventilation (IPPV) with and without addition of positive end-expiratory pressure (PEEP) for comparison. After IPPV and SB there was no change in the clearance rate of either 99mTcO4- or 99mTc-DTPA. After IPPV + PEEP and HPOV (8 and 16 Hz), there was an increase in the clearance rate of 99mTc-DTPA, but an increase in clearance rate of 99mTcO4- was seen after IPPV + PEEP only. In a separate group of dogs an increase in end-tidal lung volume was demonstrated after 4 h of ventilation with IPPV + PEEP (but not after HFOV), and this may account for the measured increase in 99mTcO4- clearance. We conclude that an increase in 99mTc-DTPA clearance rate after HFOV signifies an increase in pulmonary epithelial permeability, possibly through the mechanism of damage to the intercellular junctions during HFOV.

Altered pulmonary epithelial permeability in canine radiation lung injury.

A radioaerosol scanning technique measuring regional clearance of sodium pertechnetate (99mTcO-4) and 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) was used to assess changes in canine pulmonary epithelial permeability following lung irradiation. Doses of 2,000 cGy (11 dogs), 1,000 cGy (2 dogs), and 500 cGy (2 dogs) were given in one fraction to either the entire right hemithorax (500 cGy) or the right lower lung (1,000 and 2,000 cGy). Radioaerosol scans, chest roentgenograms, and computerized tomograms (CT) were obtained before and serially after irradiation. A dose of 2,000 cGy resulted in a decrease in regional pulmonary epithelial permeability to both 99mTcO4- and 99mTc-DTPA; both showed significant decreases from the 2nd wk postirradiation onward. In comparison, CT and chest roentgenogram did not become abnormal until 7.1 +/- 2.8 (SD) and 8.2 +/- 2.6 wk, respectively. Doses of 1,000 and 500 cGy produced reversible decreases in 99mTcO4- clearance. Lung morphology showed definite changes of radiation pneumonitis after 2,000 and 1,000 cGy but not after 500 cGy at approximately 9, 17, and 12 wk postirradiation, respectively. These results suggest that dose-dependent changes in pulmonary physiology may precede obvious structural alterations in radiation lung injury.

Canine tracheal mucus transport of particulate pollutants: comparison of radiolabeled corn pollen, ragweed pollen, asbestos, silica, and talc to Dowex anion exchange particles.

Canine tracheal mucous transport rates of each of two organic (corn and ragweed pollen), and three inorganic (chrysotile asbestos fibers, silica, and talc), 99mTc labeled pollutants were simultaneously measured against those of 125I labeled Dowex anion exchange resin particles in healthy animals. The method of labeling of the pollutants with 99mTc is described. With the exception of ragweed pollen, which moved 15% faster than the reference marker (P <.02), we found no difference in the transport rates of these particulate pollutants and the reference marker. We conclude that the particulate pollutants studied are handled by the mucociliary system in a similar fashion, and that the transport rates of Dowex particles represent valid measurements of the transport rates of these pollutants.

Single photon emission tomography of lungs imaged with 99mTc-labeled aerosol.

The use of single photon emission computed tomography (SPECT) and radiolabeled aerosols for lung scanning offers theoretical advantages over conventional gamma camera imaging. We verified the feasibility of using such a system to define particle deposition. First, in two dogs, we detected segments of the lung which had received fewer radiolabeled particles because of obstruction to the airway by a balloon or a lead shot. Second, by comparing axial computed tomography (CT) images to their SPECT counterparts, we were able to demonstrate the effectiveness of SPECT in delineating large thoracic structures such as major vessels and central airways. We feel that SPECT also provides excellent images for qualitative work. We then used SPECT to study aerosol deposition in 13 normal subjects and eight patients. We found that the normal subjects had uniform peripheral deposition, but the eight with abnormal lung function had patchy deposition. Furthermore, we found that regions of abnormal deposition not seen on conventional views could be delineated by tomography. We conclude that this technique will improve our understanding of aerosol deposition in humans by providing a three-dimensional visualization of the lungs and airways.

Relationship between regional ventilation and aerosol deposition in tidal breathing.

The regional distribution of the deposition of 1.2 micron particles of 99mTc sulfur colloid inhaled by tidal breathing was compared with the distribution of ventilation as measured by a 133Xe washout technique. Twelve subjects were studied, 6 with normal pulmonary function tests, 5 with air-flow limitation, and 1 with unilateral phrenic nerve paralysis. Both xenon and aerosol were inhaled at tidal volume by the subjects while seated upright. A large field gamma camera acquired posterior scans. Thirteen experiments were also done on 7 dogs: 1 with extrathoracic obstruction of the airway to 1 lung, and 12 with bronchoconstriction from the instillation of methacholine chloride into the airways of a lower lobe. Two of these dogs were studied with a gamma camera system, and the others were studied with a Picker multi-probe system. Both in humans and in dogs, an increase in time constant, which indicated a decrease in ventilation, was associated with an increase in peripheral aerosol deposition when normalized for ventilation. It is suggested that the increased residence time is responsible for the increased deposition in regions that received lesser ventilation.

Radioiodinated N-[3-(4-morpholino)propyl]-N-methyl-2-hydroxy-5-iodo-3-methylbenzylamine (ERC9): a new potential melanoma imaging agent.

The role of nuclear medicine in the management of patients with malignant melanoma has expanded in recent years with the introduction of lymphoscintigraphy and sentinel lymph node biopsy, intense interest in positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxyglucose (18F-FDG) as a tracer, and encouraging reports of several new single-photon-emitting radiopharmaceuticals. While PET imaging with FDG exhibits a high sensitivity for imaging patients with melanoma, specificity may not be as high and access to the technology remains limited. Single-photon emission tomography (SPET) imaging remains standard technology for most nuclear medicine departments. We report a novel radiopharmaceutical--radioiodinated N-[3-(4-morpholino)-propyl]-N-methyl-2-hydroxy-5-iodo-3-methylbenzylamine (ERC9)--which appears to show a sensitivity and specificity that are commensurate with expectations of a radiopharmaceutical for routine clinical imaging. In this phase II trial, 110 patients at risk for recurrence, with suspected recurrence or being restaged have been imaged with this novel tracer, demonstrating an overall sensitivity of 91% and specificity of 89%. The results of our study support a phase III trial to establish the clinical role of ERC9 in staging melanoma patients at presentation who are at high risk for metastasis, or restaging patients with known relapse to assess the extent of their disease, particularly if therapy or enrollment into a clinical trial is being considered.

Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate.

We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and 99m technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function.