Analysis of the early blood kinetics of 99mTc-GSA and its verification: new one-compartment model and regression equation.

Technetium-99m-galactosyl human serum albumin (99mTc-GSA) is a radiopharmaceutical that binds to asialoglycoprotein receptors in the hepatocyte membrane; the level of 99mTc-GSA accumulation in the liver correlates well with the parameters of hepatic function tests. We hypothesized that the early blood kinetics of 99mTc-GSA could be described by a simple one-compartment model expressed as an offset + a monoexponential function (y=y0 +Ae(-alpha)t). The aims of this study were to assess the validity of this hypothesis using sequentially measured blood levels of 99mTc-GSA, which were approximated by a regression expression, and to analyse the regression equation. 99mTc-GSA levels were measured in blood samples collected from 30 patients with liver disease. From sequential changes in radioactivity up to 30 min after injection, a regression equation expressed as an offset+ a monoexponential function was calculated and evaluated by multiple correlation coefficients and absolute deviations (% error). The liver uptake rate 15 min after injection of 99mTc-GSA (liver uptake rate 15, UTR 15) was calculated from the regression equation in each case. The respective relationships of this parameter to the coefficient [A] and gradient [alpha] were evaluated. In all cases, the measured values of radioactivity in blood samples could be fitted to an offset + a monoexponential function. The validity of our hypothesis was supported by examining regression equations calculated from blood 99mTc-GSA levels. Analysis of the regression equations suggested a potential for a new index of hepatic functional reserve.

[Regional cerebral blood flow of the basal ganglia and thalamus measured using Xe-CT].

Cerebral blood flow (CBF) images obtained using Xe-CT have a much higher spatial resolution than SPECT or PET images. The regional CBF (rCBF) of deep brain regions, the basal ganglia and thalamus, was able to be measured using Xe-CT in 6 subjects. Average rCBF was 87.1 +/- 20.7 ml/100 g/min in the caudate nucleus, 83.5 +/- 15.8 ml/100 g/min in the putamen, 50.0 +/- 8.7 ml/100 g/min in the globus pallidus and 88.9 +/- 12.4 ml/100 g/min in the thalamus. The average rCBF value of the globus pallidus was lower than the values of the caudate nucleus, putamen and thalamus. These observations may be explained by reduced cellularity of the globus pallidus in comparison to the other regions. SPECT and PET are not able to clearly demonstrate the globus pallidus on CBF images. However, precise rCBF values can be measured in the globus pallidus using Xe-CT.

Response to percutaneous transhepatic portal embolization: new proposed parameters by 99mTc-GSA SPECT and their usefulness in prognostic estimation after hepatectomy.

UNLABELLED: Accumulation of 99mTc-galactosyl human serum albumin (GSA) in the liver correlates well with the parameters of hepatic function tests. We performed 99mTC-GSA SPECT before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe before extensive hepatic resection and analyzed the responses of new proposed parameters in the future remnant lobe that showed hypertrophy. The aim of this study was to evaluate the usefulness of these parameters in prognostic estimation after hepatectomy. METHODS: We studied 10 patients with cholangiocarcinoma and 1 patient with metastatic liver tumor from sigmoid colon cancer. 99mTc-GSA SPECT was performed immediately before and 2 wk after PTPE. We analyzed the responses of the liver uptake ratio (LUR), functional volume (FV), and liver uptake density (LUD) in the future remnant lobe and evaluated their relationship with the prognosis after subsequent hepatic resection. RESULTS: LUR and FV increased slightly but were not associated with the prognosis after hepatic resection. LUD increased significantly after PTPE in the group showing a good outcome after hepatic resection but decreased after PTPE in the group showing a poor outcome (post-PTPE LUD, 0.064+/-0.017%/cm3 versus 0.035+/-0.006%/ cm3, P<0.05; response rate, 22.2%+/-11.9% versus -8.9%+/-17.6%, P<0.01). CONCLUSION: Responses of LUD to PTPE before hepatic resection in the future remnant lobe represent changes in asialoglycoprotein receptor activity per hepatocyte and predict responses to subsequent hepatic resection. LUD may be an important parameter for determining the outcome after hepatic resection.

[The calculated reference value of the tubular extraction rate in infants and children: an attempt to use a new regression equation].

This study was designed to investigate the empirical tubular extraction rate (TER) of the normal renal function in childhood and then propose a new equation to obtain TER theoretically. The empirical TER was calculated using Russell's method for determination of single-sample plasma clearance and 99mTc-MAG3 in 40 patients with renal disease younger than 10 years of age who were classified as having normal renal function using diagnostic criteria defined by the Paediatric Task Group of EANM. First, we investigated the relationships of the empirical value of absolute TER to age, body weight, body surface area (BSA) and distribution volume. Next we investigated the relationships of the empirical value of BSA corrected TER to age, body weight, BSA and distribution volume. Linear relationship was indicated between the absolute TER and each body dimensional factors, especially regarding to BSA, its correlation coefficient was 0.90 (p value). The BSA-corrected TER showed a logarithmic relationship with BSA, but linear regression did not show any significant correlation. Therefore, it was thought that the normal value of TER could be calculated theoretically using the body surface area, and here we proposed the following linear regression equation: Theoretical TER (ml/min/1.73 m2) = (-39.8 + 257.2 x BSA)/BSA/1.73 The theoretical TER could be one of the reference values of the renal function in the period of the renal maturation.

Possible association between delusional disorder, somatic type and reduced regional cerebral blood flow.

1. A 78-year-old female with DDST and pain disorder was treated by clomipramine 20-100 mg/day. The hypochondriacal delusion was completely resolved, while the pains were partially resolved. 2. The SPECT using Xe-133 taken at the early stage of clomipramine treatment, when she still had hypochondriacal delusions, showed markedly reduced rCBF in the temporal and parietal lobes, with predominance on the left hemisphere. Meanwhile, the SPECT taken after resolution of the hypochondriacal delusions showed a marked improvement in the reduced rCBF. 3. This report suggests that DDST has some association with reduced rCBF in the temporal and parietal lobes.

[Evaluation of the liver uptake rate measured by 99mTc-GSA SPECT to assess liver function].

Whether the global liver uptake rate of 99mTc-GSA directly measured by SPECT is useful as a new index of liver function was evaluated in comparison with biochemical test results (PT%, ChE, Alb, ICG R15, KICG) and Child classification. 99mTc-GSA SPECT was performed in 157 patients with diffuse hepatic disease or hepatobiliary tumor, and two indices, namely the global liver uptake rate measured by SPECT 15 minutes after intravenous injection of 99mTc-GSA (LUS 15) and liver uptake per volume (liver uptake density) were examined. Both LUS 15 and liver uptake density were significantly correlated with biochemical test results and Child classification. In particular, close relationships between LUS 15 and ICGR15 (r = -0.720, p < 0.0001), LUS 15 and KICG (r = -0.750, p < 0.0001), and between LUS 15 and ChE (r = 0.720, p < 0.0001), indicate that LUS 15 is a useful index to evaluate liver function. Moreover, the local liver uptake rate measured by SPECT represented regional liver function and was considered a useful index to predict the function of the remnant liver after invasive treatment such as surgery.

[Discrepancy between 99mTc-HMPAO and 99mTc-ECD in Alzheimer's disease: does the retention mechanism depend on the disease?].

The discrepancy between 99mTc-hexamethyl-propyleneamine oxime (HMPAO) and 99mTc-ethyl cysteinate dimer (ECD) in Alzheimer's disease (AD) was investigated and compared with in cerebral ischemic disease (CID). The subjects were fourteen AD and thirty-one CID patients with clinically reasonable rCBF reduced lesion on 133Xe SPECT. The subjects did not include the cases of acute and subacute CID. These SPECT were performed within two weeks by ring-type dynamic SPECT (HEADTOME, Shimadzu, Japan). In the CID group, both of HMPAO and ECD SPECT could hardly detect the mildly reduced rCBF lesion on 133Xe SPECT but normal on X-CT. In the case of AD group, the rCBF-reduced lesion on 133Xe SPECT could be detected well by ECD SPECT, but the HMPAO hardly detected the reduced lesion. This discrepancy between HMPAO and ECD may be due to the difference of the retention mechanism. In the case of AD, the injury of esterase activity that participates with the ECD retention may be more notable than that of glutathione activity for the HMPAO retention. These results suggest suggest that the reduction of ECD or HMPAO density depends directly on the insufficiency of retention mechanism rather the than rCBF reduction. And the insufficiency of this retention mechanism depends on also type of the disease i.e. AD or CID.

[Improved the accuracy of 99mTc-MAG3 plasma clearance method: the problem of the calculated plasma volume and its modification].

The 99mTc-MAG3 plasma clearance method (MPC method), reported by Oriuchi et al., is a simple and useful count-based gamma camera method for calculating the 99mTc-MAG3 plasma clearance (CLMAG). However, a discrepancy of CLMAG calculated by MPC method (MPC-CLMAG) from the tubular extraction rate (TER) calculated by Russell's single-sample clearance determination (Russell-TER) was noted. The calculated plasma volume is assumed to be the cause. Since the plasma volume is reported to have a linear correlation with body surface area, Dissmann's formula was applied to calculate the plasma volume. Then Dissmann's formula was replaced by Ogawa's formula in the MPC method, and the procedure was then called the modified MPC method. The CLMAG were obtained using MPC method, modified MPC method and the TER was obtained Russell's method in 95 patients with urological disorders. Then the MPC-CLMAG and modified MPC-CLMAG were compared with Russell-TER. Comparison of the MPC-CLMAG with the Russell-TER demonstrated a coefficient of correlation of 0.82, but dissociation of the slope of regression lines was found between males and females. The modified MPC-CLMAG improved the coefficient of correlation to 0.92, and diminished the dissociation of the slope of regression lines between males and females. We verified that the dissociation was due to the plasma volume calculated by Ogawa's formula. Ogawa's formula included hematocrit, body weight, body height and different coefficients for gender. The plasma volume calculated by Ogawa's formula were lower in males and higher in females than that calculated by Dissmann's formula. And marked discrepancy in the plasma volume in patients with a body surface area below 0.5 m2 was observed. So the MPC method might become more accurate by substituting Dissmann's formula for Ogawa's formula resolting in a method that is applicable to both males and females, children and adults in clinical use.

Modification of measurement of effective renal plasma flow from blood pool clearance curve of I-123-orthoiodohippurate using single blood sampling.

The methods of measuring effective renal plasma flow (ERPF) based on the two-compartment analysis of plasma clearance of I-123-orthoiodohippurate (OIH) disregard the distribution of I-123-OIH to erythrocytes, resulting in over-estimation of ERPF. In this study, a new simple modification was established to obtain accurate ERPF. Intercompartmental clearance rates among plasma, erythrocytes, and extracellular fluid were determined through in vitro and in vivo experiments to enable the three-compartment analysis of plasma clearance curves of I-123-OIH using multiple blood samplings in comparison with the two-compartment analysis. Multiplying renal blood flow derived from two-compartment analysis of the whole blood clearance curve by (1-hematocrit/100) was a new modification for measuring ERPF to reduce the complexity of three-compartment analysis and to supplement the distribution of I-123-OIH to erythrocytes. Comparing ERPF derived from the modified two-compartment analysis with that from three-compartment analysis demonstrated good agreement (r = 0.883, p = 0.001) between the two methods. ERPF derived by this new method was also compared with the clearance of paraaminohippurate (PAH), resulting in a regression line which was much closer to unity and a better correlation between them (r = 0.926) than that between PAH clearance and ERPF (r = 0.909) derived from conventional two-compartment analysis.

Changes in regional brain activity in major depression after successful treatment with antidepressant drugs.

Relative regional cerebral blood flow was measured with single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) in 16 patients with major depression while they were in the depressed state as well as in remission. All patients were closely matched with regard to medication status. In the depressed state, significant reductions in tracer uptake were found in the left superior frontal, bilateral parietal and right lateral temporal cortex. During remission, significant increases in uptake were found in the left superior frontal, right parietal and right lateral temporal cortex. There were no significant differences in tracer uptake between patients in remission and controls. These findings suggest that the regional decreases in tracer uptake observed in the depressed state might be a state-related abnormality.

[Improvement of a filter and the effect on the TECHNEGAS leakage].

We previously reported about the room air contamination during ventilation study using the TECHNEGAS system. Main cause of the contamination with radioactive gas were leakage through the filter and expiration of the patient after the inhalation. Then, a new type filter was developed to reduce the radioactive leakage. The efficacy and usefulness of the new type filter was examined. The radioactive leakage through the new filter was markedly reduced to 1/6 compared with the old type. But the air resistance of passage was increased over two times of the old type. This resistance is not able to disregard on respiratory physiology. Improvement to reduce the resistance is desirable.

[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

[Correlation of regional cerebral blood flow between Xe-CT and 133Xe-SPECT: validity of Xe-CT in evaluating rCBF].

Stable xenon-enhanced computed tomography (Xe-CT), a relatively inexpensive addition of an inhalation system to the CT, has been a common method for the measurement of rCBF in recent years. Although the 133Xe clearance method has been accepted as a standard method since the 1970s, a comparative study of rCBF between Xe-CT and 133Xe-SPECT has not been reported. We studied the validity of Xe-CT for evaluating rCBF in comparison with 133Xe-SPECT. From May 1993 to December 1994, rCBF studies in 31 cases were performed using both methods within one month of each other. We evaluated rCBF of the unilateral cerebral hemisphere at a slice of OM + 80 mm level. Finally, Eleven cases were excluded from the analysis because of the existence of ventricle in the image and/or discrepancy in the clinical state between the two examinations. In the remaining 20 cases, there was a significant correlation of rCBF between Xe-CT (Y) and 133Xe-SPECT(X)(Y = 0.95X-1.7, r = 0.86, p < 0.001, n = 40). The results supported the usefulness of Xe-CT for the quantitative assessment of rCBF. As compared with SPECT, Xe-CT offers the advantages of much higher spatial resolution, allowing more precise reference of flow and anatomy, and providing quantitative information on rCBF in deeper regions of the brain.

A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

[Quantitative assessment of an increase of myocardial 99mTc-MIBI accumulation during exercise--usefulness of response rate].

The increase of myocardial 99mTc-MIBI accumulation during exercise was evaluated quantitatively, and the feasibility of response rate as a noninvasive marker of coronary stenosis was tested. Myocardial perfusion imaging with 99mTc-MIBI during exercise and at rest was performed in patients with suspected coronary artery disease. A dose of 296 MBq of 99mTc-MIBI was injected intravenously at maximal treadmill exercise, and myocardial image was obtained 90 min later (1st image). Then, 740 MBq of 99mTc-MIBI was administered at rest, and myocardial image was repeated (2nd image). These images were corrected for a decay and injected dose, and the 1st image was subtracted from the 2nd image to obtain the rest image. An increase of myocardial accumulation of 99mTc-MIBI during exercise was defined as (exercise image-rest image) x 100/rest image (response rate). A response rate of a patient with normal coronary artery was 102%, whereas a response rate in the area of severe coronary stenosis was 21% in a patients with angina pectoris. After successful PTCA to a stenosed coronary artery, a response rate increased to 75% in this patient. Coronary perfusion reserve during exercise can be assessed noninvasively by 99mTc-MIBI. Response rate of 99mTc-MIBI provides additional information to conventional perfusion imaging and may be a new marker of severity of coronary artery disease.

[Contamination levels to room air arising from the use of 99mTc-gas and prevention from the contamination].

99mTc-gas (TECHNEGAS) is a 99mTc-labeled micro-aerosol which is considered to have different behavior from 133Xe or 81mKr gas. In order to estimate contamination levels to room air arising from the use of 99mTc-gas, filtered expired air during administration and 1, 2, 3, 5, 10 min after the administration were collected in each polyethylene bag. Radioactivities of the polyethylene bags, used filter and the lung were measured with 3-head scintillation camera. The activity of the expired air diminished within 6-10 min and about 5% of whole discharged 99mTc-gas was released to room air. The activity of the used filter was two times of the lung. According to these results, it is recommended that the 99mTc-gas may be administrated in a exclusive room. The administrated patient and used filter must be remain in the exclusive room.

[Immunochemiluminometric assay (Automated Chemiluminescence System ACS: 180) for CEA].

We examined Automated Chemiluminescence System ACS: 180 for CEA assay, especially about confidence of the functional sensitivity. Serum CEA levels of normal subjects and patients were measured not only with ACS: 180 but also with immunoradiometric assay (CEA kit [Daiichi] II). Using ACS: 180 assay for CEA, intra-assay coefficients of variation (C.V.s) were 4.06% at 1.97 ng/ml, 1.62% at 17.3 ng/ml, and 2.28% at 81.3 ng/ml. Interassay C.V.s were 4.02% at 1.99 ng/ml, 1.21% at 16.5 ng/ml, and 3.44% at 79.4 ng/ml. The detection limit (functional sensitivity) of ACS: 180 assay for CEA was 0.4 ng/ml by the precision profile. The coefficient of correlation of 164 sera, which CEA values were among 0.4-100 ng/ml (working range of ACS: 180), between with ACS: 180 and with CEA kit [Daiichi] II was R = 0.942, y = 1.07 x +0.09 (p < 0.05). Seven (13.2%) normal subjects (n = 53) and 45 (34.1%) patients with malignant diseases (n = 132) had higher serum CEA levels than the cut off value (2.5 ng/ml). The sera of 82 malignant patients who had both pre- and post-operation sample were determined. Sixty-five patients of them were decrease after operation. These results of ACS: 180 resembled to that of CEA kit [Daiichi] II. We conclude that ACS: 180 for CEA assay was precise enough to measure below the cut off value, and had good performance of its speed (short incubation) and convenience.

[Investigation of discrepancy between 99mTc-HMPAO and 133Xe rCBF SPECT; a comparative study with X-ray CT findings].

To investigate the discrepancy between 99mTc-hexamethylpropyleneamine oxime (HMPAO) and 133Xe rCBF SPECT, the findings of thirty patients with reasonable rCBF reduction on 133Xe SPECT were compared with HMPAO SPECT and X-ray CT. The subjects did not include the cases of acute and subacute CVD. Both SPECT were performed within two weeks by ring-type dynamic SPECT (HEADTOME, Simadzu, Japan). In comparison between the SPECT findings by 133Xe and 99mTc-HMPAO, the subjects were classified into three groups as follow. Group A: Similar findings in the both SPECT were noted in 6 cases (20%). Group B: Smaller findings on HMPAO SPECT than that by 133Xe were in 11 cases (37%). Group C: No findings of rCBF reduction on HMPAO SPECT were in 13 cases (43%). The rCBF of the lesion measured by 133Xe SPECT in the group C was 24-35 ml/100 g/min. The density of HMPAO in the lesion did not correlate with the rCBF value. Only the severity of CT findings tend to correlate with the density of HMPAO. These results suggest that the reduction of HMPAO density depends directly on some kind of neural injury rather than the rCBF value. The injury may be caused by the flow reduction under the threshold of each neural cell. So the correlation between HMPAO density and actual rCBF might show like sigmoid curve. Then the HMPAO SPECT might directly reflect the regional extraction and fixation ratio, and the reduction of blood flow cause the minute neural-injury in the lesion of moderately reduced rCBF.

[Xenon-133 rCBF SPECT by newly designed bolus inhalation method].

Single photon emission computed tomography (SPECT) with 133Xe gas inhalation method enables measurement of regional cerebral blood flow (rCBF) quantitatively. But this method is inferior to the method with 99mTc-HMPAO or 123I-IMP in the quality of images. Efficient administration of 133Xe gas more than usual is supposed to improve quality of SPECT images. In this study we designed bolus inhalation method, a new method to efficiently administer 133Xe gas of usual dose (1,850 MBq), and examined its fundamental aspects and clinical feasibility. The method was initiated by bolus administration of 133Xe gas synchronously in inspiration phase via a small tube connected to a mouthpiece and was followed by steady breathing of the gas in a closed circuit with a spiro-bag. Introduction of this method provided almost twofold increase in count ratio at the head in comparison with a conventional inhalation method. Consequently, considerable improvement in the quality of rCBF images was achieved by optimization of a reconstruction filter of SPECT.

[Xe-133 inhalation single photon emission computerized tomography in manic-depressive illness].

We measured regional cerebral blood flow (rCBF) in depressed patients using Xe-133 inhalation single photon emission computerized tomography (SPECT; HEADTOME). Thirty-two medicated mildly depressed patients, six bipolar (BP) and 26 unipolar (UP), and 20 control subjects participated in the study. Compared to the controls, UP patients showed a significant decrease of rCBF in the bilateral frontal and the parietal regions, which were dominant in the left hemisphere, while BP patients showed no decrease of rCBF and mean CBF. Comparison of rCBF between before and after treatment with antidepressants in 8 depressed patients revealed an increased rCBF after the improvement in the left superior frontal, the left parietal and the right temporal regions which are critical areas for the development of depression.