Pulmonary inhalation scintigraphy using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) aerosol

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) is lipophilic substance and permeates through the alveolar epithelium via intracellular transport, whereas 99mTc-DTPA is water-soluble substance and permeates through the alveolar epithelium via paracellular transport. We performed inhalation lung imaging using 123I-IMP and 99mTc-DTPA in order to assess alveolar epithelial permeability in 4 patients with restrictive ventilatory impairment, and 5 volunteers including one smoker. The time-activity (T/A) curves of 123I-IMP were well fitted into two compartments, first and slow, by least-squares fit technique, in contrast to 99mTc-DTPA fitted well with one compartment. In 4 normal volunteers, the T/A curves of the lower pulmonary fields declined faster than those of other pulmonary fields. In 99mTc-DTPA studies, the Kep values of patients with restrictive ventilatory impairment (n = 4) were higher than those of normal volunteers (n = 4) (2.14 +/- 0.30 x 10(-4) vs 1.48 +/- 0.41 x 10(-4), p less than 0.005). On the other hand, in 123I-IMP studies, the Kep values of the patients were much lower than those of normal volunteers (6.79 +/- 0.55 x 10(-5) vs 1.52 +/- 0.45 x 10(-3), p less than 0.005).     

SPECT images after intravenous injection of 99mTc-DTPA in lung tumors--comparison with delayed 123I-IMP lung scintigraphy

The aim of this study was to assess the efficacy of SPECT imaging of the thorax with 99mTc-DTPA, which accumulates at sites of increased capillary permeability and expanded extracellular space, by comparing it with delayed 123I-IMP lung scintigraphy. We have previously reported that increased uptake on delayed 123I-IMP lung scintigraphy was associated with atelectasis and inflammation. Thirteen patients with lung cancer (4 with atelectasis and 3 with pleurisy), one patient with malignant lymphoma complicated by pneumonia and pleurisy, and one patient with pneumonia were studied. 99mTc-DTPA scintigraphy was performed twice, 20-160 minutes and 2-4 hours after the intravenous administration of 370 MBq of 99mTc-DTPA. 123I-IMP scintigraphy was performed 24 hours after the intravenous injection of 111 MBq of 123I-IMP. SPECT images were obtained with both types of scintigraphy. 99mTc-DTPA scintigraphy was compared with 123I-IMP scintigraphy for its ability to detect atelectasis and pneumonia. All patients showed increased accumulation corresponding to the lesions on both 123I-IMP and 99mTc-DTPA scintigraphy. 123I-IMP scintigraphy showed a defect corresponding to the tumor with increased accumulation around the tumor, whereas 99mTc-DTPA scintigraphy showed accumulation corresponding to the tumor. Ten of 11 tumors showed accumulation of an intensity equal to that of the soft tissue of the chest wall on 20-60 min 99mTc-DTPA images. The 2-4 hr images showed that 99mTc-DTPA leaked from the periphery of the tumor toward its center. All the patients with pleurisy showed increased accumulation in effusion on 2-4 hr 99mTc-DTPA scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)     

"Luxury perfusion" with 99mTc-HMPAO and 123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.     

Evaluation of the alveolar-capillary membrane permeability using 99mTc-HMPAO aerosols in severe diffuse interstitial fibrosis

Local information on permeability of the alveolar-capillary barrier (PACB) can be ascertained by parametric images, after inhalation of radioarosols and computer processing. Our aim is to compare the results of 99mTc-HMPAO aerosols on PACB studies with those of 99mTc-DTPA aerosols, a standard technique. We compared the two techniques in separate samples: normal controls and patients with severe lung interstitial pathologies. Perfusion studies using 99mTc-MAA have also been performed in all patients. The aerosols were produced using ultrasound and lowered surface tension solution of 99mTc-HMPAO and 99mTc-DTPA. The time-activity curves (TACs) for every pixel on the lung area were used to calculate the half-disappearance times (T1/2). Parametric images were then generated with those times. The comparison of the results obtained with 99mTc-HMPAO and 99mTc-DTPA aerosols suggests that the first ones are more specific for local alterations of the lung epithelial transport in the pathologies studied. This method distinguishes between permeability deficiency due to local perfusion decrease and ACB deterioration.     

Pulmonary clearance of 99mTc-DTPA aerosol in patients with progressive systemic scleroderma]

Alveolar epithelial permeability was assessed in 32 patients with progressive systemic scleroderma (PSS), using 99mTc-DTPA aerosol. Immediately after the inhalation of 99mTc-DTPA aerosol for 3 to 6 minutes under normal tidal breathing, lung was imaged sequentially for 30 minutes from the posterior by a gamma camera and exponential fitting was processed on the time activity curve. T1/2 (min) was used as a parameter for the evaluation of permeability of alveolar epithelium. Patients with collagen disease showed shorter T1/2 (T1/2 = 43.7 +/- 23.8 min) than the normal volunteers (T1/2 = 76.8 +/- 8.7 min). No significant difference was observed between patients with or without interstitial changes on the chest CT. Significant correlation was not observed between T1/2 and %VC or %DLco. In 8 cases, studies were repeated in the interval of 3 to 19 months. Improvement of T1/2 was seen in 4 cases, independent of CT findings. These results suggest that 99mTc-DTPA aerosol clearance study provides information independent from other lung examinations, and may be useful for the assessment of lung interstitial changes in patients with PSS.     

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.     

Uptake of SPECT radiopharmaceuticals in neocortical brain cultures

The uptake, retention and uptake antagonism of 201Tl-DDC, 201Tl-Cl, 123I-IMP, 99mTc-HMPAO and 99mTc-O4- were compared in rat neocortex cultures. 201Tl-DDC and 123I-IMP revealed the highest uptake of radioactivity in the cultures. 99mTc-HMPAO and 123I-IMP showed the highest retention of radioactivity within the tissue in washout experiments. Blocking of bioelectric activity by tetrodotoxin did not significantly affect the uptake of the radiopharmaceuticals (RPHA). Inhibition of Na-K-ATPase by ouabain inhibited the uptake of 201Tl-Cl (77%) and 201Tl-DDC (27%). Imipramine showed a significantly stronger inhibitory effect on 123I-IMP uptake in comparison with the effect on other RPHA. 99mTc-O4- was not concentrated within the cultured tissue. Under the in vitro conditions used in this study, the various RPHA were characterised by distinct differences in their interaction with cortical brain tissue.     

Detection of alveolar epithelial injury by<Superscript>99m</Superscript>Tc-DTPA radioaerosol inhalation lung scan following blunt chest trauma

DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99mTc-DTPA aerosol inhalation scintigraphy was used to assesss the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53+/-13 yrs) who were referred to the emergency department in our hospital participated in this tsudy. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T1/2 value of the whole lung was 63+/-19 minutes (min), and thirtieth day mean T1/2 value was 67+/-21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60+/-0.05, and 0.63+/-0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99mTc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase.     

Favorable biodistribution of99mTc-ECD for brain SPECT comparing with123I-IMP using alternative body scan

In order to evaluate the lung and brain uptake of 99mTc ethyl cysteinate dimer (99mTc-ECD) and N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP), alternative body scans were carried out in 15 cases of cerebrovascular disease. The biodistribution of 99mTc-ECD was 5.5 +/- 0.7%, 3.8 +/- 0.7% in the brain; 13.1 +/- 3.7%, 2.2 +/- 1.2%, in the lung at 15 min and at 4 hours, respectively, whereas that of 123I-IMP was 3.9 +/- 1.4%, 5.0 +/- 1.0% in the brain; 32.2 +/- 7.6%, 12.7 +/- 3.3%, in the lung at 15 min and at 4 hours, respectively. 99mTc-ECD accumulated in comparatively high amounts in the brain but remained low in the lung in the early image compared to 123I-IMP. However there was a high inverse correlation between brain and lung uptake of 123I-IMP (r = -0.82), but not of 99mTc-ECD (r = -0.18). We concluded that 99mTc-ECD had a better biodistribution in terms of low lung accumulation than 123I-IMP in brain SPECT.     

Cerebral perfusion scintigraphy in patients with cerebrovascular disease by using 99mTc-ECD: comparative study with 123I-IMP SPECT

99mTc-ECD SPECT was performed in 19 patients with cerebrovascular disease, and location, extent, and severity of the lesions on 99mTc-ECD SPECT were compared with those on 123I-IMP SPECT. The initial brain uptake was 5.5 +/- 0.7% of the injected dose at 10 minutes after injection, 5.3 +/- 1.3% at 90 minutes, and clearance from the brain is slow. The distribution in the brain was changed, especially washout from the thalamus was slower than that from other regions. The count ratio of perfusion defect to normal area (D/N) on 99mTc-ECD SPECT was unchanged over the time, and had no significant differences from that on 123I-IMP SPECT. 99mTc-ECD SPECT was superior in detection of the lesion in the basal ganglia, and showed the images with superior spatial resolution due to physical characteristics of 99mTc. However, mild ischemic lesion and peri-infarct area was not clearly visualized, while 123I-IMP SPECT could demonstrate these lesions with better contrast.     

Use of iodine-123 metaiodobenzylguanidine scintigraphy for the detection of amiodarone induced pulmonary toxicity in a rabbit model: A comparative study with technetium-99m diethyltriaminepenta acetic acid radioaerosol scintigraphy

The purpose of the study was; (i) to determine whether 123I-MIBG scintigraphy is sensitive for detection of amiodarone induced pulmonary toxicity (AIPT) and (ii) to compare it with 99mTc-DTPA radioaerosol. Twelve white New Zealand rabbit with initial mean body weight 4.24 +/- 0.47 g were divided into two groups. AIPT group (n = 7) was administered amiodarone (20 mg/kg BW). The control group (n = 5) received the same amount of 0.9% saline. All animals underwent 123I-MIBG and 99mTc-DTPA radioaerosol scintigraphy at the end of the treatment period. 123I-MIBG static thorax images were obtained during 10 minutes at 15 minutes and 3-hours after intravenous injection of the radiopharmaceutical. Lung to heart ratios (LHR) and lung to mediastinum ratios (LMR), and retention index (LRI) of 123I-MIBG were determined. Two days after 123I-MIBG scintigraphy, 99mTc-DTPA radioaerosol scintigraphy was performed, and clearance from the lungs was measured for 10 min (1 min/frame) following termination of inhalation. 123I-MIBG lung retention index (LRI) was significantly higher in the AIPT group than the control (61 +/- 4.6 vs. 40 +/- 4.5, p = 0.01). Early LHR and LMR were significantly lower in the AIPT group than in the control group (p = 0.04, p = 0.01, respectively), whereas those of late LHR and LMR were not significantly different. T1/2 values of DTPA clearance were significantly increased in AIPT group according to the control group (55 +/- 7.2 vs. 86.6 +/- 18.5, p = 0.02). 123I-MIBG scintigraphy is a valuable tool for detecting AIPT in a rabbit model. Additionally, 99mTc-DTPA radioaerosol scintigraphy is an excellent comprehensive investigational tool for detecting AIPT with the added advantage of lower cost.     

Single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propyleneamine oxime in patients with ischemic cerebral diseases: comparative study of N-isopropyl-p-[123I]-iodoamphetamine and 99mTc-DTPA SPECT

In order to confirm the diagnosis and clarify the pathophysiology in the ischemic lesions in brain, 99mTc-PAO SPECT was performed in 42 patients with ischemic cerebral diseases, and the findings on 99mTc-PAO SPECT were compared with those on 123I-IMP or 99mTc-DTPA SPECT, and on X-CT. Furthermore, count ratio of ischemic lesion to normal contralateral region (I/N) was used for the evaluation of the detectability in the lesions on 99mTc-PAO or 123I-IMP SPECT, and less than 0.95 of I/N ratio was defined as the decreased accumulation. The detectability of ischemic lesion in brain with 99mTc-PAO SPECT was 80%, which was superior to that (60%) of LDA on X-CT. Especially, 99mTc-PAO SPECT was useful in cases which were examined early after the onset of the attack. On the other hand, 123I-IMP SPECT showed the best result (88%) in the detectability, and furthermore I/N ratio on 123I-IMP SPECT was lower than that on 99mTc-PAO SPECT. In the delayed phase on 123I-IMP SPECT the redistribution was observed in 30%, while on 99mTc-PAO SPECT it was done in none of them. The accumulation of 99mTc-DTPA in brain was found in 6 of 14 cases (43%), and 2 cases among them also showed the accumulation of 99mTc-PAO in the ischemic lesion. In such cases the destruction of BBB might be considered as the cause of the accumulation of 99mTc-PAO. Thus, 99mTc-PAO SPECT was thought to be useful method in clinical studies of the ischemic cerebral diseases.     

New insights on flow-independent mechanisms of 99mTc-HMPAO retention in nervous tissue: in vitro study.

SPECT using 99mTc-hexamethyl propyleneamine oxime (HMPAO) mainly reflects regional cerebral blood flow, however metabolic abnormalities also affect the retention of 99mTc-HMPAO. METHODS: To rule out any flow factor, a test-tube model was used to evaluate the effects of metabolic alterations both on intracellular trapping of 99mTc-HMPAO and on extracellular glutamate and lactate dehydrogenase (LDH) outflow from rat brain slices. RESULTS: Under control conditions, slices took up 7.0%+/-1.4% of 99mTc-HMPAO contained in the medium, whereas prelabeled slices released 10.8%+/-2.6% of their radioactive content; glutamate and LDH outflow were 49.1+/-21.6 pmol/mg protein/ min and 4.8+/-0.9 U/L/mg protein/min, respectively. The control medium was altered by adding a metabolic poison (5 mmol/L azide), removing glucose and replacing O2 with N2 to mimic ischemia (in vitro ischemia) and replacing Krebs solution with hypotonic medium to evoke cell lysis. Both azide and in vitro ischemia induced a significant increase in 99mTc-HMPAO release (15.8%+/-3.3% and 18.3%+/-6.2%, respectively), without any modification in LDH efflux. However, only azide reduced the uptake of the tracer. Conversely, glutamate outflow was massive during in vitro ischemia and was far lower during azide treatment. Under hypotonic medium conditions, the release of 99mTc-HMPAO, glutamate and LDH were dramatically increased. Surprisingly, a two-fold increase of 99mTc-HMPAO uptake was also found. When 1 mmol/L glutathione was added to the medium, to convert native lipophilic 99mTc-HMPAO into hydrophilic derivatives, tracer uptake was inhibited both under control and hypotonic medium conditions. CONCLUSION: This study provides evidence that not only poisoning of the tissue but also in vitro ischemia induced a reduction of 99mTc-HMPAO retention. Moreover, we demonstrated that injuries causing cell membrane disruption led to hyperfixation of 99mTc-HMPAO.     

Altered kinetics of 123I-IMP in irradiated rabbit lungs.

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.     

Pulmonary clearance of technetium 99m diethylene triamine penta-acetic acid aerosol in patients with amiodarone pneumonitis

Amiodarone pneumonitis is a serious complication that may lead to fatal lung fibrosis. In an attempt to diagnose this condition as early as possible, the technetium-99m-labelled diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol washout rates of 10 non-smoking normal volunteers (group 1), 10 non-smoking patients on a long-term amiodarone regimen with dilated cardiomyopathy but no congestive heart failure (group II) and 10 patients with amiodarone pneumonitis (group III) were compared. Spirometric measurements, as percentage predicted, were higher in group I than in group III (P less than 0.05). The global mean effective half-lives of 99mTc-DTPA aerosol for both lungs together in minutes were 65 +/- 14, 55 +/- 16 and 27 +/- 4 for groups I, II and III, respectively. Group III values were significantly lower than those of groups I and II (P less than 0.05). Our results demonstrated that amiodarone pneumonitis alters the alveolar-capillary membrane permeability to hydrophilic molecules. The pulmonary clearance of 99mTc-DTPA aerosol is a useful test in the differentiation of patients on a long-term amiodarone regimen without side effects from patients with amiodarone pneumonitis. The test is rapid, easy to perform and has the potential for playing an important role in deciding which patients should discontinue therapy.     

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.     

The behavior of 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain

99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how 99mTc-HMPAO changed in the blood and brain. The 99mTc-HMPAO, which was prepared by adding of 99mTcO4- to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed 99mTc, and 99mTc-pertechnetate. The percentage of the primary complex in 99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When 99mTc-HMPAO was injected into patients, 99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma, 99mTc was found to be associated with proteins such as albumin and globulin. 99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of 99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific 99mTc binding protein was present in the brain. Considering the instability of 99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing 99mTc-HMPAO to pass through the BBB and to be fixed in the brain.     

Clinical and experimental studies on the mechanism of abnormal accumulation in lung scanning with 123I-IMP.

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.     

Impaired lung epithelial permeability in hepatitis C virus antibody positive patients detected by 99mTc-DTPA aerosol scintigraphy

Chronic hepatitis C virus (HCV) infection has been recently identified as an aetiological agent in idiopathic pulmonary fibrosis. The present study was designed to determine the pulmonary clearance rate of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) in asymptomatic HCV antibody positive (HCV Ab+) patients and the role of 99mTc-DTPA aerosol scintigraphy in the early detection of lung involvement. Twenty-six non-smoker HCV Ab+ and HCV-RNA (+) patients (20 female, six male; aged 43+/-11 years), with no clinical pulmonary symptoms, and normal radiological findings, were studied. Thirty-one healthy non-smoker volunteers (24 female, seven male; aged 40+/-10 years) were taken as a control group. 99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests were performed in all patients and in controls. On the basis of the scintigrams the percentage decline in activity per minute (Kep) was evaluated, which represented an accurate parameter of lung membrane permeability. The mean Kep values of healthy controls (0.78+/-0.13 for left lung, 0.79+/-0.14 for right lung) were significantly lower than HCV Ab+ patients (1.10+/-0.31 for left lung, 1.11+/-0.34 for right lung, P<0.001). But no significant change was observed in PFT (P>0.05). We conclude that subclinical alveolitis and/or interstitial lung disease may be present in patients with HCV Ab+, since it is known that an increase in the epithelial permeability of the lung is an early manifestation of interstitial disease.     

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.