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In order to perform a less invasive determination of regional cerebral blood flow (rCBF) using I-123-IMP, we used the lung clearance curve as a substitute for the arterial blood activity curve as an input function. We assumed that a major portion of the intravenously injected I-123-IMP initially accumulates in the lung and then is gradually cleared from the lung pool to enter the systemic circulation. In this case lung clearance could be considered nearly equal to the integral of arterial blood activity shown during the examination. We used a single probe detector to obtain the lung clearance curve as the difference between sequential lung activity and peak lung activity. The absolute value of the sequential change in arterial blood activity was estimated from the differentiated lung clearance curve compared with the arterial blood activity that was estimated by actual blood sampling once during the examination. The rCBF was calculated by the thus estimated arterial blood activity curve and brain activity by SPECT image using the microsphere model. The values of rCBF obtained by this method were similar to those obtained by the continuous arterial sampling method, and this lung monitoring method was thought to be applicable to clinical use.

Radiation-induced alteration of intra-pulmonary kinetics of 123I-IMP was investigated in 11 rabbits received a 50 Gy dose of radiation to the hemithorax. In all of these rabbits examined during 3-17 weeks following the irradiation, an abnormal accumulation was seen in the irradiated lung on the delayed image obtained 60 minutes after the injection of 123I-IMP. The time-activity curves in the irradiated lung following the injection had shallower downslopes of both the initial fast phase and the following slow phase than those of non-irradiated lung, and finally 123I-IMP uptake of the irradiated lung exceeded that of the normal lung. Chest radiographies all of 11 rabbits showed no abnormal shadow and histological studies in 6 of them revealed a relatively slight change or injury of the irradiated lung during 3-17 weeks. These results indicate that this agent may be useful for detecting and assessing relatively early and slight lung injury induced by irradiation.

Radiation-induced alteration of intrapulmonary kinetics of 123I-IMP was investigated in 11 rabbits receiving a 50 Gy dose of radiation to one lung. In all 13 examinations of these rabbits, 3-17 weeks following radiation, the delayed images of 123I-IMP lung scintigrams showed abnormal accumulation in the irradiated lungs. The time-activity curves of the irradiated lung following injection of 123I-IMP had shallower downslopes of both the initial fast phase and the following slow phase than those of the non-irradiated lung. Finally the radioactivity of the irradiated lung exceeded that of the normal lung. The altered intrapulmonary kinetics of 123I-IMP in the irradiated lung was clearly confirmed. 99Tcm-MAA lung perfusion scintigrams showed reduced uptake in the irradiated lungs; the uptake decreased with time following radiation. Pulmonary arterial perfusion was considered to influence the distribution and kinetics of 123I-IMP, however, those of 123I-IMP did not reflect only the pulmonary arterial perfusion observed by 99Tcm-MAA scintigrams. Chest radiography and histological studies revealed a relatively slight change or injury of the irradiated lung in these rabbits. These results indicate that this agent could be useful in detecting and assessing early lung injury induced by radiation, and will give us pathological information in addition to lung perfusion in the peripheral area where the large 99Tcm-MAA molecule cannot reach.

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.

The uptake and binding mechanism of biogenic amines in the lungs has been studied extensively with no conclusive results. The competition between N-isopropyl-123I-p-iodo amphetamines (123I-IMP) and propranolol and 123I-IMP and ketamine, in the lungs suggest that the pKa value of the biogenic amines has a significant role to play in the mechanism of uptake and retention of biogenic amines in the lungs.

To investigate the mechanism of intrapulmonary kinetics of N-isopropyl-p-123I-iodoamphetamine (123I-IMP), we performed lung scanning with 123I-IMP in 13 rabbits in which a unilateral bronchus was occluded by a balloon catheter. In 9 rabbits, on the delayed distribution images, an abnormal accumulation of 123I-IMP was detected in the hypoperfusion area of the peripheral lung field of the occluded bronchus, which was detected on lung perfusion images with 99mTc-MAA. Comparison of early (a summation image during 20 seconds immediately after injection) and delayed (a summation image from 70 to 90 minutes after injection) distribution images confirmed that during this period, 123I-IMP accumulated in the area of reduced distribution of 123I-IMP. Moreover, at the site of abnormal accumulation, washout of 123I-IMP from the lung was delayed compared with that in the normal lung field. We find this experimental study is similar to the results in 63 clinical cases, which we have reported previously, and confirm that pulmonary arterial perfusion, especially hypoperfusion, influences the intrapulmonary kinetics of 123I-IMP.

In the experiment using guinea pigs, the accumulated portions of IMP after 125I-IMP microautoradiography were compared in a normal control group and a group exposed to cigarette smoke. In the smoke-exposed lung, the accumulation of silver grains were observed in the alveolar spaces and alveolar macrophages, as well as in the pulmonary capillaries and the alveolar epithelia. After the broncho-alveolar lavage (BAL), increases in alveolar macrophages, total counts of BAL fluid and counts of cell components were seen in the smoke-exposed lung. These results suggested that abnormal function of the pulmonary capillary or alveolar epithelium was wide spread in the smoke-exposed lung.

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.

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.

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.

123I-IMP is taken up by the pulmonary capillary endothelial cells during the first pass through the lung, and is slowly released from them. To look up the factors which influence on the prolonged 123I-IMP retention in the diseased lung, we examined the correlation between the 123I-IMP uptake during the first pass and the 123I-IMP retention. Patients with bronchial asthma had no abnormal finding in the chest X-ray photograph. However 123I-IMP release from their lungs was delayed. Some patients show a tendency that 123I-IMP uptake during the first pass was uneven, which suggested the change in amine uptake function of endothelial cells. However their correlation coefficients between the uptake during the first pass and the prolonged retention were very small. It was considered that the prolonged 123I-IMP retention in the diseased lung was not explained only by the change in uptake function of pulmonary capillary endothelial cell.

Experimental study on N-isopropyl-p-iodoamphetamine lung uptake was performed by means of analyzing microautoradiography obtained by administering 125I-IMP to Wistar male rats. In the normal rat lung at one minute after the intravenous injection of 125I-IMP, there is increased grain density in the interstitial space including the capillary lumen and interalveolar septum, but not in the alveolar space. On the other hand, at 24 hours after the intravenous injection, increased grain density was noted in the alveolar space of the rat lungs which had received a dose of 10 Gy to the unilateral one. But, definite difference was not found in grain density between the irradiated and non-irradiated lung. The results indicate that part of IMP which was taken up by the endothelial cell is capable of passing through capillary-alveolar barrier.

The movement of N-isopropyl-p[123I] iodoamphetamine (I-123 IMP) in the lungs was studied. The half time of I-123 IMP release (T 1/2) was delayed in the fibrosis and the sarcoidosis. There was a relation between the prolongation of T 1/2 and the radiographic finding. It was considered that T 1/2 was useful for the objective estimation of the change in the lungs. The adsorption of I-123 IMP to the alveolar cells was much higher than to the circulating leukocytes. It was considered that the accumulation and retention of I-123 IMP in the lungs had relation to the alveolar cells.

Aiming at clinical application of N-isopropyl-p-[I-123]-iodoamphetamine (I-123 IMP) to lung diseases intrapulmonary kinetics of I-123 IMP was studied. Dynamic lung scintigraphy was performed after intravenous injection of 3 MBq I-123 IMP in six normal volunteers and twenty patients with interstitial lung diseases. Simultaneously data were acquired in a data processor with 60-sec intervals over the period of 60 min. Time-activity curves of two areas of each lung field were obtained to calculate k values by monoexponential fitting method. In patients with interstitial lung diseases k values were significantly decreased (p less than 0.001) (0.995 X 10(-2) +/- 0.26 X 10(-2) as compared with those (1.602 X 10(-2) +/- 0.24 X 10(-2) in normal volunteers. For the assessment of capillary blood volume in the lung Tc-99m Sn colloids (SN) were given i.v. before I-123 IMP in 16 patients. There was a high correlation between regional uptake ratio of I-123 IMP and Tc-99m Sn colloids (SN) both at 1 min (n = 64; r = 0.91) and 25 min (n = 64; r = 0.93) after injection. The k values of IMP clearance curves were correlative to diffusing capacity at rest for CO (DLCO) (r = 0.71, p less than 0.01), vital capacity (r = 0.53, p less than 0.05) and forced expiratory volume in 1 sec (r = 0.58, p less than 0.05). These results suggest that the lung clearance of I-123 IMP reflect the severity of the endothelial cell injury which cause decrease in the capillary blood volume in interstitial lung diseases. Dynamic lung scintigraphy with I-123 IMP should prove useful for monitoring disease activity of interstitial lung diseases providing a new parameters to assess a non-respiratory lung function.

A 67-year-old female with radiation pneumonitis in the right upper lobe underwent lung scanning and bronchoalveolar lavage 4 hours after the intravenous injection of 123I-IMP. The lung scanning showed increased accumulation of 123I-IMP, corresponding with the area of radiation pneumonitis. The ratios of radioactivities of the cellular and noncellular components in the bronchoalveolar lavage fluid to that of the serum, were 27.0 and 0.39, respectively. Our results suggest that 123I-IMP or its metabolites are transported through alveolo-capillary barrier and taken up by free cells in the alveolar space after 123I-IMP has been bound to nonspecific receptor sites in the endothelial cell in the capillary lumen.

N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) was examined for its relevancy as a labeling medium of lung scintigraphy in 30 patients with lung diseases and 20 healthy subjects. Lung diseases were classified into carcinoma and diffuse lung disease, and the all subjects with normal lung were classified into smokers and nonsmokers. To assess the reduction curve of 123I-IMP, mean transit time was calculated. Forced spirography was performed and spirographic values were analyzed. Spirographic parameters examined were vital capacity percent (%VC), forced expiratory volume in 1 sec divided by forced vital capacity (%) (FEV1.0%), and blood gas data. In the correlation matrix, the mean transit time was correlated with blood gas data, and not with %VC or FEV1.0%. In patients with lung diseases, the mean transit time was significantly prolonged; however, the difference was not significant between groups of carcinoma and benign disease, and between groups of smokers and nonsmokers. Wash-out images were obtained by the subtraction technique using the first frame image and 100-min delayed image. In patients with lung carcinoma, 87.5% of the tumors were depicted on wash-out images. The lesions were also depicted well in benign lung diseases. But among findings of wash-out image by 123I-IMP, air trapping image by 133Xe study and XCT study, there are some discordances to be clarified.

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.

The first-pass pulmonary extraction values of N-Isopropyl-123I-p-Iodoamphetamine (123I-IMP) in pretreated dogs decreases from 90 to 62% as the amount of propranolol increases from 0 to 20 mg. The first-pass pulmonary extraction values of 123I-IMP in dogs with a simultaneous bolus injection of propranolol decreases from 90 to 62% as the amount of propranolol increases from 0 to 10 mg. The pulmonary extraction of 123I-IMP with a simultaneous bolus injection of ketamine and 123I-IMP decreases from 90 to 64% as the ketamine dose increases from 0 to 100 mg. These results suggest that the pulmonary uptake of 123I-IMP may be at least partially mediated by receptors. They also indicate that endothelial metabolic cell function may be a useful index of early lung pathology. Furthermore, studies of the degree of lung uptake may be a sensitive index of pathologic states in which alterations of amine binding sites have occurred.

We studied the accumulated portion and the movement of I-123 IMP in the lung. Ten subjects were studied. They were four patients with fibrosing lung disease, two with lung cancer, and four with other lung disease. They underwent the broncho-alveolar lavage (BAL) for the diagnosis of their disease. 1.5 mCi of I-123 IMP was injected into the ante-cubital vein. The BAL examination was carried out about 40 minutes after the injection of I-123 IMP. The subjects' blood was sampled at the same time. The total BAL liquid (BAL-T) was divided into the fluid component (BAL-F) and the cell component (BAL-C) by centrifugation. The radioactivities in BAL-T, BAL-F, BAL-C, and serum (B-S) were measured by the well-counter. The average of BAL-T/B-S, BAL-F/B-S and BAL-C/B-S were 6.86, 4.26 and 2.71 respectively. It was confirmed that I-123 IMP was transported from the pulmonary capillary to the alveolar space and was taken up by the alveolar cells. It was considered that the analysis of the I-123 IMP release from the lung showed not only the endothelial cell uptake function but also the interstitial and material cells' amine transport and uptake function.

Radioiodinated metaiodobenzylguanidine (MIBG) has been shown to be extracted in the lung by an active, sodium-dependent, saturable transport system similar to that which extracts norepinephrine. Accordingly, first transit uptake of MIBG has been investigated as a method for in vivo evaluation of pulmonary biogenic amine metabolism. Issues that still must be resolved include the degree to which MIBG extraction is affected by simple loss of available vascular surface (in distinction to changes in amine metabolism). If MIBG lung extraction is altered by loss of pulmonary vascular surface alone, then a tracer must be found that can serve as a simultaneous monitor of vascular surface loss in order to allow normalization of the MIBG data. One tracer with such potential is radioiodinated iodoamphetamine (IMP). Accordingly, an experimental model of pulmonary vascular surface loss (lobar ligatures) was applied in an isolated-perfused lung model with simultaneous administration of MIBG and IMP. A linear relationship was found between MIBG extraction and percent lung surface loss by weight (n = 21, r = 0.75, P less than 0.05). Addition of IMP (1 or 10 microM) to media containing MIBG (1 microM) (n = 28) inhibited overall MIBG extraction, but decreases in MIBG uptake with vascular surface loss were otherwise parallel to those in experiments without IMP. IMP, however, did not adequately reflect vascular surface loss at the concentrations used in this study (extraction of IMP 1 microM = 31.2% +/- 12.9% in control vs 32.7% +/- 7.7% with greater than 50% lung surface loss, n = 18, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The accumulation of venously injected 123I-IMP in the lung was studied. Between 30 and 50 min after the injection of the 1.5 mCi 123I-IMP, the concentration of 123I-IMP in the broncho-alveolar lavage fluid were much higher than in the blood. It was considered that 123I-IMP was transported into the alveolar spaces and was absorbed by the alveolar cells. The half time (T1/2) of the 123I-IMP release from the lung between 10 and 25 min immediately after the injection was calculated. In normal subjects the T1/2 ranged between 25 and 44 min and was prolonged in subjects with pulmonary fibrosis, sarcoidosis, and allergic alveolitis. It was considered that the retention of 123I-IMP was related not only to the endothelial cells, but also to the alveolar cells. It was considered that the analysis of the lung release of 123I-IMP forms a new lung dysfunction index.