Biomedical subjects
H Saji
Publications and source records attributed to H Saji.
[Current and future radiopharmaceuticals for brain functional studies with PET and SPECT].
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A strategy for the study of cerebral amino acid transport using iodine-123-labeled amino acid radiopharmaceutical: 3-iodo-alpha-methyl-L-tyrosine.
We examined the brain accumulation of iodine-123-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) in mice and rats. I-L-AMT showed high brain accumulation in mice, and in rats; rat brain uptake index exceeded that of 14C-L-tyrosine. The brain uptake index and the brain slice studies indicated the affinity of I-L-AMT for carrier-mediated and stereoselective active transport systems, respectively; both operating across the blood-brain barrier and cell membranes of the brain. The tissue homogenate analysis revealed that most of the accumulated radioactivity belonged to intact I-L-AMT, an indication of its stability. Thus, 123I-L-AMT appears to be a useful radiopharmaceutical for the selective measurement of cerebral amino acid transport.
Ligandin binding phthalein complexone complex of technetium for hepatic function studies.
In our pursuit for liver functional diagnosis, development of bifunctional radiopharmaceutical containing iminodiacetic acid (IDA), as the technetium chelating site along with phthalein or fluorescein structure, the skeleton of BSP and Rose Bengal, long used for the assessment of liver function is considered. Among the various PC, PPC, TPC and calcein IDA derivatives commercially available, 99mTc-PC (PC: 3,3'-bis(N, N-dicarboxymethylaminomethyl)o-cresolphthalein) showed the highest hepatobiliary excretion. The functionality of the various technetium labeled phthalein and fluorescein IDA derivatives was evaluated by competitive BSP binding studies and by comparative binding with the hepatocyte specific protein, ligandin.
Monoiodo-D-tyrosine, an artificial amino acid radiopharmaceutical for selective measurement of membrane amino acid transport in the pancreas.
Using 11C-labeled natural amino acids, the functional diagnosis of tissue metabolism has been actively studied. Our interest has been focused on developing a clinically available 123I-labeled artificial amino acid with a single metabolic function. For this study, [123I]3-iodo-D-tyrosine ([123I]D-MIT) was selected. In vitro and in vivo studies using 125I-labeled D-MIT indicated that it showed a high pancreatic accumulation, selective affinity for membrane active transport systems, and was stable against enzymatic deiodination. A canine scintigraphic study using 123I-labeled D-MIT and kinetic analysis showed that it behaved as an "artificial amino acid" radiopharmaceutical with selective membrane amino acid transport affinity in the pancreas.
Human pancreas scintigraphy using iodine-123-labeled HIPDM and SPECT.
The pancreatic affinity of iodine-123-labeled HIPDM (N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propane diamine) ([123I]HIPDM) was studied in 18 cases (5 normal volunteers, 7 cases with pancreas cancer, and 6 with chronic pancreatitis). In the normal cases, the pancreas was visualized in the planar images as early as 3 hr, and again at 20 hr postinjection. Single-photon emission computed tomography (SPECT) performed following 3-hr planar scintigraphy, provided excellent pancreas images without an overlap of activity in the liver or spleen. The mean pancreas-to-liver (P/L) ratio was 1.26 +/- 0.22 in normal controls. With the exception of one case of massive calcification in the pancreas, the entire pancreas could be observed in the cases with chronic pancreatitis, but the P/L ratio was 0.74 +/- 0.15, significantly lower than that of normal cases. Defective areas of the distal portion of the pancreas were clearly seen in those with cancer of the pancreas. The results of our study indicate that [123I] HIPDM may have clinical potential as a human pancreas imaging agent.
[Fatty acid metabolism using C-11 palmitate: (1). Resting study].
Serial dynamic images were obtained at rest following intravenous injection of 185-370 MBq (5-10 mCi) of 11C-palmitate for 40-50 minutes in 3 normal subjects and 6 patients with coronary artery disease. Due to the rapid clearance of activity from the blood, myocardial images were observed within 5 minutes after the injection in each case. The time activity curve of each myocardial region indicates biexponential clearance. The early clearance half time (Te 1/2) was similar in normal myocardium (18.8 +/- 6.0 min), ischemic myocardium (19.3 +/- 5.8 min) and infarcted myocardium (15.5 +/- 6.0 min). The late clearance half time (Tl 1/2) was also similar among these groups (81.4 +/- 36.0, 66.9 +/- 25.7 and 57.8 +/- 37.4, respectively). However, the residual fraction (%E) was slightly lower in the ischemic myocardium (19.6 +/- 11.0%) (p less than 0.05), indicating decreased beta oxidation in the former. Although positron emission tomography using 11C-palmitate may permit assessment of fatty acid metabolism, the parameters in this study were greatly fluctuated at rest among the normal, ischemic and infarcted myocardium. Further investigations under various interventions may be warranted.
Positron emission tomography using fluorine-18 deoxyglucose in evaluation of coronary artery bypass grafting.
To assess the clinical value of positron emission tomography (PET) in the evaluation of coronary artery bypass grafting (CABG), PET perfusion and metabolic imaging using nitrogen-13 ammonia and fluorine-18 deoxyglucose (FDG) was performed before and 5 to 7 weeks after CABG in 22 patients with coronary artery disease. Postoperative improvement in hypoperfusion was observed more often in the metabolically active segments (62%) than in the inactive segments (27%) on the preoperative PET study (p less than 0.05). Similarly, the postoperative lessening of wall motion abnormality was observed more often in the metabolically active segments (78%) than in the inactive segments (22%) (p less than 0.001). Of 19 asynergic segments showing increased FDG uptake before operation, the postoperative PET revealed a decrease in FDG uptake in 13 (68%) and persistent uptake in 6 (32%). The improvement in asynergy was observed in all the segments that showed a postoperative decrease in FDG uptake, but in only 50% of those with persistent uptake (p less than 0.01). On the other hand, 4 of 5 segments showing a new FDG uptake after operation revealed further wall motion abnormality. Furthermore, the segments metabolically active before operation were more likely to have patent grafts (95%) than the metabolically inactive segments (70%) (p less than 0.05). Thus, preoperative metabolic imaging using PET appears to be useful for predicting the response to CABG. Improvement in metabolic derangement was associated with improvement in regional function after CABG.
Design, synthesis and 64Cu labeling of fatty acid analogs containing dithiosemicarbazone chelate.
For the development of 62Cu labeled fatty acid analogs, two fatty acid analogs, containing dithiosemicarbazone (DTS) molecule as the 62Cu coordinating site, were designed and synthesized: a fatty acid analog containing DTS molecule at the omega-position, (a) the 12,13-dioxotetradecanoic acid di(N-methyl-thiosemicarbazone) (FA-DTS), and an omega-phenyl fatty acid analog containing DTS molecule at the para-position, (b) the p-carboxyundecylphenylglyoxal-di (N-methylthiosemicarbazone] (PFA-DTS). FA-DTS was synthesized by the reaction of ethyl diethoxyacetate with ethyl 11-bromonundecanate by successive decarboxylation and hydrolysis and final condensation with N-methylthiosemicarbazide. PFA-DTS was synthesized by the Friedel-Craft acylation of ethyl 11-phenylundecanate, selenium oxidation of the acetophenone derivative, followed by the condensation with N-methylthiosemicarbazide. Radiolabeling of FA-DTS and PFA-DTS with [64Cu]copper acetate was simple, rapid and quantitative. When injected into mice, both compounds were distributed and retained in the myocardium. These results offer a good basis for further development of 62Cu labeled fatty acid analogs.
The detection of an antibody against IgA allotype A2M 2 and a study of the Am genetic marker among the Han Chinese population.
The serum of a woman was found by the Ouchterlony double-diffusion and the hemagglutination inhibition (HAI) methods to have immunoglobulin A (IgA) deficiency. Further investigation using the hemagglutination (HA) test with red cells coated with IgA myeloma proteins of different specificities showed that the serum agglutinated only IgA2-, A2M-1, and A2M 2-coated cells. The patterns of the HAI test with a reference panel confirmed the presence of two specificities. One was anti-IgA2 and the other was a rare antibody against the allotype A2M 2. The anti-A2M 2 was used for population studies. Testing of the Han Chinese population, including family studies, confirms that A2M.1 and A2M.2 have an autosomal dominant mode of inheritance and are controlled by a codominant allele. The distribution of the two Am genetic markers among the Han Chinese population demonstrated A2M.1 with a gene frequency of 0.553 and A2M.2 with a gene frequency of 0.447 (chi 2 = 0.145, 0.80 greater than p greater than 0.70).
New platelet antigen, Siba, involved in platelet transfusion refractoriness in a Japanese man.
Siba, a new platelet-specific alloantigen involved in a case of platelet transfusion refractoriness is reported. The IgG platelet alloantibody was detected in a multiply transfused patient of Japanese extraction (Sib), by the presence of HLA antibodies. After transfusion of HLA-compatible platelets, the patient suffered from refractoriness. Adsorption studies with pooled lymphocytes showed that the serum contained anti-platelet activity. Family studies indicate that Siba is inherited as an autosomal codominant trait and separate from HLA and Baka. As of this report, segregation from Zw(PlA) and Yuk (Pen) antigen systems have not yet been determined. The gene frequency of Siba in the Japanese population is estimated to be 0.136.
[Assessment of myocardial viability by quantitative analysis of stress Tl-SPECT--comparison with FDG-PET].
Stress Tl-201 tomography (SPECT) is widely used for evaluating myocardial viability. To assess its value, redistribution (RD) on SPECT was compared with metabolic imaging using FDG. Thirty patients with coronary artery disease underwent stress-3 hour Tl-201 SPECT and PET using N-13 ammonia and FDG. RD was classified into 4 grading, including complete RD (CR), incomplete RD (IR), persistent defect (PD) and additional minimal RD (MR) defined as no definite RD on visual analysis but faint RD with Bull's eye quantitative analysis (QNT). All but one segment with CR or IR were viable regions (normal or ischemic regions) by PET. Of 74 segments without RD on visual analysis, 31 segments (42%) had RD by QNT (MR). All of them were viable regions by PET. Thus, QNT identified 31 segments (63%) of the metabolically viable segments which the visual Tl-201 analysis did not show RD and classified as myocardial scar. However, even such QNT cannot detect ischemic myocardium in 18 segments (42%) containing metabolic activity on PET. These data indicate that QNT of RD on Tl-201 SPECT is considered as a valuable means for assessing myocardial ischemia.
Regional dynamics of N-isopropyl-(123I)p-iodoamphetamine in human brain.
Regional cerebral dynamics of N-isopropyl-(123I)p-iodoamphetamine (IMP) in the human brain were studied using a multi-detector single photon emission computed tomography (SPECT) scanner in 35 subjects both normal and with a variety of neurological conditions. Distribution of IMP in the brain was also compared with regional cerebral blood flow (CBF) measured by positron emission tomography (PET) in 15 of these 35 cases. A significant regional difference in temporal changes of radioactivity was observed among normal brain structures. A rapid increase with early washout of the tracer was shown in the cerebellum and the occipital cortex, while the basal ganglia revealed a relatively slow increase and prolonged retention, indicating the regional difference in extraction and/or retention of IMP among the cerebral tissues. In cases with unilateral hypoperfusion, the percentage of the activity in the lesion to that in the contralateral normal cortex on the early SPECT was correlated well with that on CBF measured by PET (r = 0.870, p less than 0.001). However, the contrast on the SPECT image decreased with time after injection; 84.0 +/- 7.4% on the SPECT at 5-20 min scan, 87.6 +/- 7.6% at 35-50 min scan and 96.2 +/- 6.3% at 5 hr scan. In a case with a brain tumor having high blood flow documented by PET, increased accumulation of IMP was observed in the tumor on the early images obtained within 20 min followed by a rapid washout. These findings suggested altered extraction and/or retention of IMP in normal and diseased tissues, and these factors should be considered for the assessment of distribution and redistribution of IMP.
Value of rest-stress myocardial positron tomography using nitrogen-13 ammonia for the preoperative prediction of reversible asynergy.
To determine the predictive value of stress [13N]ammonia positron emission tomography (PET) for reversible ischemia, 31 patients with coronary artery disease underwent rest-stress [13N]ammonia PET before and after coronary artery bypass surgery. The circumferential profile analysis was applied to determine the presence of transient defect (TD) and persistent defect (PD) preoperatively, and the fate of perfusion abnormality and asynergy after the surgery was assessed. Preoperative PET demonstrated 100 segments with perfusion abnormalities, including 69 TD and 31 PD. Fifty-six of the 69 TD (81%) improved in regional perfusion, while only four of 31 PD (13%) improved in perfusion postoperatively (p less than 0.001). Of 75 segments showing regional asynergy on contrast or radionuclide ventriculography preoperatively, 34 of 48 segments with TD (71%) improved in asynergy, while only five of 27 segments with PD (19%) improved in asynergy postoperatively (p less than 0.001). Stress-delayed 201TI tomography was performed in 22 of them. The predictive values for improvement in perfusion (77%) and asynergy (65%) were similar as those by [13N]ammonia PET (81% and 71%, respectively). However, the predictive values for no improvement in perfusion and asynergy by 201TI tended to be low (66% and 58%, respectively), as compared to those in 13N ammonia PET (87%; p less than 0.05 and 81%; p = 0.09, respectively). We conclude that an accurate prediction of reversible ischemia and asynergy can be achieved with rest-stress [13N]ammonia PET. Particularly, it can identify irreversible areas more accurately than the commonly performed stress-delayed 201TI imaging.
Quantitative analysis of regional wall motion by gated myocardial positron emission tomography: validation and comparison with left ventriculography.
Electrocardiographically gated positron emission tomography (ECG-gated PET) with [13N] ammonia was used to assess regional myocardial wall motion of left ventricle (LV) based on a nongeometric method in nine healthy volunteers and 16 patients with coronary artery disease (CAD). Three transverse sections (upper, middle, and lower) with 16-mm intervals at end-diastole (ED) and end-systole (ES) were analyzed. The LV wall was divided into eight segments with every 30 degrees from septal wall to lateral wall. Based on circumferential profile analysis, the percent count increase [( ES count - ED count) divided ED count x 100) in each segment was analyzed as an index of regional wall motion. In the study of normal controls, the percent count increase was the lowest (32.9 +/- 7.2%) at septal wall of the lower slice and the highest (72.8 +/- 26.5%) at lateral wall of the upper slice (p less than 0.01). In five normal controls, the percent count increase was compared with the percent systolic wall thickening analyzed by magnetic resonance imaging, and a good correlation was observed (r = 0.84). In the study of patients with CAD, the percent count increase was compared with wall motion assessed by left ventriculography (LVG). The percent count increase significantly decreased as wall motion on LVG worsened. In addition, the value in normal controls tended to be higher than that in the segments with normal wall motion in patients with CAD. Thus, quantitative analysis of regional wall thickening was feasible by ECG-gated PET, which should be useful for combined analysis of regional function, perfusion and metabolism in patients with CAD.
Relation of left ventricular perfusion and wall motion with metabolic activity in persistent defects on thallium-201 tomography in healed myocardial infarction.
Myocardial viability in persistent thallium (TI)-201 defect is a controversial subject. To assess metabolic activity in segments with persistent defect, stress TI-201 tomography and positron emission tomography using nitrogen-13 ammonia and fluorine-18 2-fluoro-deoxyglucose (FDG) were performed in 28 patients with healed myocardial infarction. The segments with TI-201 perfusion defect in electrocardiogram-determined infarcted areas were selected for assessment. Stress perfusion defect was detected in 61 segments by TI-201 tomography. Twenty-two patients (36%) showed transient defects with redistribution (group 1) and 39 showed persistent defects (group 2). Increase in FDG uptake was observed in 95% in group 1. Among group 2 patients, 15 segments (38%) showed an increase in FDG uptake (group 2A) while the remaining 24 (62%) did not have an increased uptake (group 2B). The decrease in nitrogen-13 ammonia perfusion was more severe in group 2B (-23 +/- 7%) than in group 2A (-13 +/- 9%) (p less than 0.005) and group 1 (-10 +/- 4%) (p less than 0.001). In addition, wall motion scores tended to be lower in group 2B (0.21 +/- 0.71), compared with group 2A (0.67 +/- 0.70) (p = 0.05) and group 1 (0.77 +/- 0.60) (p less than 0.01). These data indicate that metabolic viability was observed in approximately 40% of the segments with persistent TI-201 defect. Preservation of regional perfusion and wall motion in these areas was similar to that in areas with transient TI-201 defect.
Change of HLA phenotype in postoperative erythroderma.
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Dynamic positron emission tomography with 13N-ammonia in liver tumors.
Dynamic positron emission tomography (PET) of the liver tumor was performed with a whole body multi slice PET device and 13N-ammonia. Sixteen patients with hepatocellular carcinoma (HCC) and seven patients with metastatic liver tumor were studied. In 12 of 16 patients with HCC, in which cases rich tumor vessels and dense tumor stain were proven by hepatic angiography, the tumors showed remarkable uptake of 13N-ammonia from the first scan, whereas the radionuclide accumulation was more gradual in the other part of the liver, and high tumor to liver ratio (T/L ratio) (2.62 +/- 1.09) was observed in the 1st scan, so that the tumor was clearly visualized by high contrast. However, HCC with poor blood supply from the hepatic artery or central necrosis of the tumor were demonstrated as low T/L ratio. In seven cases with metastatic liver tumor, the accumulation of 13N-ammonia was also lower than the normal liver throughout the scan. The results suggested that hepatic arterial blood flow of the liver tumors can be assessed with dynamic PET, which may provide valuable information for the characterization of tumors as well as for the evaluation of the treatment.