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Biomedical subjects

N Shuke

Publications and source records attributed to N Shuke.

At least 55 records · Page 3Linked to original sources

Demonstration of double-chambered right ventricle on myocardial perfusion SPECT.

A 19-year-old man with a double-chambered right ventricle (DCRV) and an associated ventricular septal defect was admitted to the hospital for surgical correction. Preoperative study of myocardial perfusion with Tc-99m tetrofosmin SPECT depicted the two chambers of the right ventricle. There was a substantial differential in the radioactive uptake between these two chambers. The inflow and outflow chambers with different peak-pressures (94 and 18 mm Hg) showed different uptakes reflecting the pressure difference, which was intense in the inflow chamber and weak in the outflow.

Adult↗

Tc-99m leukocyte imaging for evaluating disease severity and monitoring treatment response in ulcerative colitis: comparison with colonoscopy.

The diagnostic value of Tc-99m leukocyte imaging for evaluating disease activity and monitoring treatment response in ulcerative colitis was compared with that of colonoscopy. A total of 48 studies were performed in 28 patients with ulcerative colitis. Forty-six studies had both Tc-99m leukocyte imaging and colonoscopy within 2 weeks of each other, and the remaining two studies had only Tc-99m leukocyte imaging. In 46 studies, semiquantitative grading of colonic radioactivity by comparison with iliac crest marrow activity on radionuclide imaging correlated well with macroscopic grading based on Matts' criteria on colonoscopy. Fourteen (82%) of 17 studies with slight colonoscopic change showed a negative result on the radionuclide image. In 15 patients treated with glucocorticoids or leukapheresis, radionuclide imaging showed nearly the same statistical results as colonoscopy in monitoring treatment response. Tc-99m leukocyte imaging could be used as an alternative to colonoscopy to evaluate the disease activity of ulcerative colitis or to monitor the treatment response, although it is insensitive for detecting disease with only slight macroscopic changes.

Adult↗

Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for radioimmunotherapy: in vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice.

Stability and immunoreactivity of 186Re-labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor-bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A murine IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re-MAG3 complex was conjugated to A7 after esterification of 186Re-MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively. Immunoreactivity of purified 186Re-MAG3-A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re-MAG3-A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at -80 degrees C could effectively prevent the radiolysis of 186Re-MAG3-A7 for 7 days. Immunoreactivity of 186Re-MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after the preparation. In colon cancer xenografted mice, 31.0% of the injected dose/g of 186Re-MAG3-A7 had accumulated in the tumors at 24 h postinjection. Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12-fold greater than the whole-body radiation dose. These in vivo characteristics were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131I-A7. Because of the better image quality of 186Re-MAG3-A7 as well as more favorable dosimetry, 186Re-MAG3-A7 would be a better choice for RIT of colon cancer than 131I-A7. These results indicated the feasibility of RIT with 186Re-MAG3-A7, though the prevention of radiolysis of the labeled antibody should be considered.

Animals↗

Persistent distension and enhanced diffusive extravasation of tumor vessels improved uniform tumor targeting of radioimmunoconjugate in mice administered with angiotensin II and kininase inhibitor.

Induced hypertension with angiotensin II (AT-II) and the inhibition of kininase with enalapril maleate may increase the tumor targeting of radiolabeled monoclonal antibodies (MAbs). We previously found that short-period infusion of 2.0 microg/kg/min of AT-II enhanced tumor targeting of MAb without an impact on normal tissue distribution. In this study, we aimed to optimize the manipulation with these agents, and examine the possible mechanism of their effects on MAb distribution. Effect of the manipulation on tissue circulation was assessed in mice bearing colon cancer xenografts by 201Tl and 99mTc-human serum albumin (HSA) as markers of tissue blood flow and tissue blood volume and/or vascular permeability. A dose finding study of enalapril ranging from 3 to 300 microg showed that 30 microg of enalapril in combination with AT-II infusion produced the best improvement in tumor uptake of 99Tc-HSA without altering 201Tl distribution, suggesting that the increase of vascular permeability was caused by enalapril. AT-II infusion for longer than 1 h affected renal blood flow and caused subcutaneous edema. Tumor uptake of (111)In-A7, a murine IgG1, was 1.62-fold improved 72 h postinjection (P < 0.001) and intratumoral distribution became uniform with 2.0 microg/kg/min of AT-II for 1 h and 30 microg of enalapril. Vessels in manipulated tumors were distended even 48 h after the cessation of AT-II infusion. In conclusion, it was suggested that persistent distension of tumor vessels and the increase of diffusive extravasation of MAb caused by short-period-induced hypertension and inhibition of bradykinin degradation produced favorable effect for the MAb distribution in tumors.

Angiotensin II↗

Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay.

UNLABELLED: The purpose of the present study was to evaluate the degree of cytological radiation damage to lymphocytes after 131I therapy using the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by 131I in vivo should result in augmentation of the cells with micronuclei. METHODS: We studied 25 patients with differentiated thyroid carcinoma who were treated with 3.7 GBq of 131I. Isolated lymphocytes collected from patients 1 wk after therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. The micronucleus number of micronuclei per 500 binucleated cells were scored by visual inspection. As controls, lymphocytes from the same patients before therapy were also studied. In an in vitro study, lymphocytes from three patients at least 3 mo after therapy were exposed to doses varying from 0.25 to 1 Gy and studied with the same method. RESULTS: The mean number (mean +/- s.d.) of micronuclei after treatment was significantly increased (p < 0.05) as compared to control subjects (15.7 +/- 2.7 vs. 5.4 +/- 1.4). Since there was an interval ranging from 6 to 20 mo (mean 11.8 mo) between the present and the last radioiodine therapy, no significant effect on the frequency of micronucleus with cumulative radiation exposure of 131I to lymphocytes was detected. Internal radiation absorbed doses estimated for 25 patients were 0.33 +/- 0.09 Gy in this external irradiation study. CONCLUSION: The relatively low frequency of lymphocyte micronuclei induced by 131I in vivo and lack of significant effect on the frequency of lymphocyte micronuclei with cumulative 131I supported the contention that short-term nonstochastic damage of this therapy with 3.7 GBq of 131I in thyroid cancer patients is minimal and reversible.

Female↗

[Simple kinetic analysis of 99mTc-GSA by direct integral linear least square regression method: calculation of hepatic blood flow and receptor index based on three-compartment model].

To obtain both hepatic blood flow and an index of asialoglycoprotein receptor amount by simple calculation in the asialoglycoprotein receptor imaging with 99mTc-DTPA-Galactosyl Human Serum Albumin (99mTc-GSA), we have tested the applicability of the direct integral linear least square regression (DILS) method based on a linear 3-compartment model (Bronqvist, 1984) to the kinetic analysis of 99mTc-GSA scintigraphy. DILS method can provide hepatic blood flow (k1) and the product of receptor amount and forward binding rate constant (k1k3/k2) as a receptor index, without requiring iterative calculation and initial estimates of the parameters. To compare DILS method with nonlinear least square regression (NLS) method as a standard, data from 35 patients with liver dysfunction were analyzed by both methods. The effect of the data noise to parameter estimate were simulated, and both DILS and NLS method could provide reliable parameter estimate which is relatively insensitive to the data noise. In estimated model parameters, both hepatic blood flow (k1) and the receptor index (k1k3/k2) showed significant correlation between 2 methods (r2 = 0.96, p < 0.0001; r2 = 0.99, p < 0.0001, respectively). We concluded that DILS method was comparable to NLS method in determination of the model parameters and could be useful in the asialoglycoprotein receptor imaging.

Adult↗

Radiotoxicity after strontium-89 therapy for bone metastases using the micronucleus assay.

UNLABELLED: The purpose of this study was to evaluate the degree of cytologic radiation damage to lymphocytes after 89Sr therapy using the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes exposed to 89Sr in vivo should result in augmentation of the number of cells with micronucleus. METHODS: We studied eight patients with painful bone metastases, who were treated with 111 MBq89Sr. Isolated lymphocytes collected from the patients 1 wk after therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. The number of micronuclei per 500 binucleated cells was scored by visual inspection. As controls, lymphocytes from the same patients before therapy were also studied. For three patients, serial blood samples were examined for a maximum of 2 mo after therapy. In an in vitro study, lymphocytes from five normal volunteers were exposed to doses varying from 0.25 to 1.0 Gy and studied with the same method. RESULTS: The mean number (+/-s.d.) of micronuclei per 500 binucleated cells after treatment was significantly increased (p<0.05) as compared to control subjects (17.1+/-3.0 compared to 6.0+/-1.7). Thereafter, the number of micronuclei recovered gradually by 6 wk following therapy and, in one case, nearly to the baseline range in 2 mo. The number of micronuclei after 0.53+/-0.13 Gy of external irradiation was nearly equivalent to that after 89Sr therapy. CONCLUSION: The relatively low frequency of lymphocyte micronuclei exposed to 89Sr in vivo supported the contention that short-term nonstochastic damage with 111 MBq89Sr in patients with painful bone metastases is minimal.

Bone Neoplasms↗

Discordant splenic uptake of Tc-99m colloid and Tc-99m denatured RBC in candidiasis-endocrinopathy syndrome.

We report discordant splenic uptake of Tc-99m colloid and Tc-99m heat-denatured red blood cells (RBC) which occurred in a 21-year-old female with candidiasis-endocrinopathy syndrome. Tc-99m colloid liver-spleen imaging showed no splenic uptake, suggesting the presence of functional asplenia. A subsequent Tc-99m heat-denatured RBC study clearly revealed a small spleen with preserved sequestrating function. These results may demonstrate that the qualitative dissociation of splenic functions in processing colloid and denatured RBC in functional asplenia: the sequestration function remains while the reticuloendothelial system is impaired.

Adult↗

Dissociation of 99mTc-ECD and 99mTc-HMPAO distributions in herpes simplex encephalitis.

In herpes simplex encephalitis (HSE), the authors noted an evident dissociation between the 99mTc-ethyl cysteinate dimer (ECD) and 99mTc-d,l-hexamethyl-propylene-amine oxime (HMPAO) single photon emission computed tomographies (SPECTs). The patient was a 5-year-old boy with diffuse type of pontine glioma, which was treated with hyperfractionated radiotherapy. Two weeks after the completion of radiation therapy, a lesion suggesting that of HSE was noted in the right fronto-temporal region on magnetic resonance images. 99mTc-HMPAO SPECT showed an increased accumulation of the tracer in this lesion. On the 99mTc-ECD dynamic SPECT, an exaggerated accumulation of the tracer was noted within 80 s of administration, followed by a rapid drop in the accumulation, resulting in a low accumulation in 10 min. It was assumed that this dissociation was due to the different mechanisms to trap HMPAO and ECD in the brain tissue.

Brain↗

Short-period-induced hypertension could improve tumor-to-nontumor ratios of radiolabeled monoclonal antibody.

This study was undertaken to find optimum period of hypertensive treatment for the improvement of tumor targeting of 111In-labeled monoclonal antibody. Angiotensin II was infused into tumor-bearing mice at an infusion rate of 2.0 micrograms/kg/min determined by the dose-finding study. The infusion was continued for up to 72 h, and biodistribution of 111In-DTPA-A7, a murine IgG1, was observed 72 h postinjection. Tumor-to-nontumor ratios were best improved with the infusion for 0.5-3 h. However, with the longer infusion, the effect deteriorated by the increase of nontumor uptakes, and body-weight loss became remarkable. It could be concluded that hypertensive treatment for a short period could be safely performed to benefit targeting of radiolabeled monoclonal antibody.

Angiotensin II↗

[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.

Adolescent↗

Brain perfusion SPECT in neuro-Behçet's disease: discordance between Tc-99m-HMPAO and Tc-99m-ECD.

A patient with neuro-Behçet's disease was studied with both Tc-99m-HMPAO and Tc-99m-ECD brain perfusion SPECT during the same time period. In Tc-99m-HMPAO SPECT, focal high uptake was observed in the left basal ganglia where MRI depicted abnormal signal intensity. Conversely, Tc-99m-ECD SPECT did not show corresponding high uptake, but demonstrated rather low uptake in contrast to the Tc-99m-HMPAO SPECT. This case suggests that Tc-99m-HMPAO and Tc-99m-ECD may show discordant distribution in inflammatory brain disease such as neuro-Behçet's disease.

Adult↗

[Pharmacokinetics of 99mTc-MAG3 and 131I-OIH: comparative study based on 2 compartment model analysis].

We studied 50 patients with mild to moderate renal dysfunction to compare pharmacokinetics of 99mTc-MAG3 with that of 131I-OIH. After simultaneous bolus injection of both 99mTc-MAG3 and 131I-OIH, 8-point venous blood sampling was performed from 2 to 44 min post injection. Aliquoted plasma samples were counted for radioactivity along with the injected standard to obtain % injected dose/ml plasma for each tracer. Using obtained time-concentration data, classical 2 compartment model analysis was performed for both tracers to obtain various pharmacokinetic parameters, including distribution volumes (Vds), inter-compartmental rate constants, and plasma clearance. In these parameters, Vd of central compartment, Vd at steady state, central to peripheral inter-compartmental rate constant, and plasma clearance were significantly larger for 131I-OIH. In all parameters, significant correlation was found between 99mTc-MAG3 and 131I-OIH. The best correlation was seen in plasma clearance (r = 0.891, p < 0.0001). Plasma clearance ratio (99mTc-MAG3/131I-OIH), however, showed weak but significant negative correlation with serum creatinine, although this correlation was not likely to affect the overall correlation of clearance between 131I-OIH and 99mTc-MAG3. From these results, we confirmed that 99mTc-MAG3 clearance could be used as an alternative to 131I-OIH clearance, although pharmacokinetic behavior of 99mTc-MAG3 was not exactly the same as that of 131I-OIH.

Adult↗

[Clinical evaluation of 99mTc-HMPAO labeled leukocyte imaging in ulcerative colitis].

Inflammatory imaging using 99mTc-HMPAO-labeled mixed leukocytes was assessed for use in treating 11 cases diagnosed as ulcerative colitis: 10 cases with total colitis and 1 with left-sided colitis. They consisted of 8 patients with relapse-remitting type and 3 with chronic continuous type. Radionuclide abdominal images were obtained at 1 hr, 4 hr and 24 hr after intravenous injection of 200 MBq prepared 99mTc leukocytes. Obvious colonic activity noted at 4 hr served as the basis for positive comparative criterion in the present study. The diagnostic efficacy of radionuclide imaging was compared with endoscopic findings (based on Matts' classification) and the clinical manifestations as reference. The sensitivity and specificity of this imaging were 83.3% and 85.7%, respectively, these values being consistent with endoscopic findings and clinical manifestations at sites of disease activity. All of positive images changed to negative after treatment by leukocyte apheresis or glucocorticoid. Based on these results, 99mTc leukocyte imaging can be used to accurately evaluate severity and treatment response in ulcerative colitis. Leukocytes may be closely related to the pathogenesis of ulcerative colitis.

Adolescent↗

Prominent uptake of Tl-201 by duodenal leiomyosarcoma after exercise myocardial perfusion study.

Thallium-201 SPECT performed preoperatively for the evaluation of myocardial ischemia in a 72-year-old man with duodenal leiomyosarcoma demonstrated prominent focal uptake in the abdomen. Comparing a transaxial slice of SPECT through the abdominal uptake to the CT scan, the uptake was confirmed to be corresponding to the tumor. The tumor was delineated clearly, in good contrast to the surrounding normal intestine, which showed far less Tl-201 uptake than the tumor. In the delayed SPECT performed 3 hours after injection, although the intestinal activity became perceptible, the tumor still could be differentiated from the surrounding normal intestine. In this case, the exercise might be attributable to the initial low Tl-201 uptake by the normal intestine, which might otherwise have been an obstacle to Tl-201 scintigraphy for abdominal tumor detection. This case suggests the use of exercise for avoiding unfavorable intestinal activity, and the possibility of Tl-201 SPECT for abdominal tumor imaging.

Aged↗

Variable portal circulation from inferior mesenteric vein assessed by per-rectal radionuclide administration.

The intrahepatic distribution of radioactivity after the per-rectal administration of 201T-chloride and/or 99Tcm-pertechnetate was investigated in 177 studies in 149 patients with no liver disease or diffuse liver disease and compared with that of 99Tcm-stannous (99Tcm-Sn) colloid scintigrams. The patients were classified into two groups: distribution of intrahepatic radioactivity of 201Tl and/or 99Tcm-pertechnetate scintigrams similar to (homogeneous) or different from (heterogeneous) that of 99Tcm-Sn-colloid scintigrams. The heterogeneous group was divided into three subgroups: increased radioactivity of the right lobe (right dominant pattern), increased radioactivity of the left lobe (left dominant pattern) and uneven distribution of radioactivity in both lobes (uneven pattern). Of the 80 patients in whom the studies were performed in the supine position at rest, 14 (17.5%) showed a heterogeneous pattern (8 right dominant, 4 left dominant, 2 uneven) and 66 (82.5%) a homogeneous pattern. In the 97 patients allowed free body movement, 6 (6.2%) showed a heterogeneous (1 right dominant, 5 left dominant) and 91 (93.8%) a homogeneous pattern. A significant difference in the incidence of heterogeneous distribution between the resting and free body movement groups was found (P < 0.05). One patient with a left dominant pattern after free body movement with 201Tl showed a right dominant pattern at rest in the 99Tcm-pertechnetate study. It is concluded that a heterogeneous intrahepatic distribution of inferior mesenteric vein blood is sometimes observed and that the distribution of portal vein blood flow seems to be affected by the patient's positioning and free body movement.

Administration, Rectal↗

Comparison of 99Tcm-pyrophosphate, 201T1 perfusion, 123I-labelled methyl-branched fatty acid and sympathetic imaging in acute coronary syndrome.

Among a group of patients (n = 15) with acute coronary syndrome, the results of using two new myocardial radiopharmaceuticals--123I-labelled 15-(p-iodo-phenyl)-3,R,S-methylpentadecanoic acid (BMIPP) and 123I-meta-iodobenzyl guanidine (MIBG)--were compared with dual 201Tl/99Tcm-pyrophosphate (Tl-PYP) imaging using single photon emission tomography (SPET). Defect scores were evaluated on a segment-by-segment basis for a total of 270 segments. For the 201Tl, BMIPP, and early and delayed MIBG studies, the mean (+/- S.D.) sums of defect scores were 9 +/- 8, 18 +/- 9, 22 +/- 12 and 29 +/- 9, respectively, revealing significantly higher scores for BMIPP and MIBG than 201Tl (P < 0.005). This was the case irrespective of various functional conditions, such as successful recanalization, failure of coronary angioplasty or restenosis. The culprit coronary artery was best identified using BMIPP, while MIBG SPET showed the most extensive defects. Normal perfusion with decreased BMIPP and MIBG uptake was frequently observed and associated with hypokinesis. 123I-BMIPP and MIBG are more sensitive for the detection of damaged myocardium, and the difference between perfusion and metabolism seems to reflect myocardial stunning.

3-Iodobenzylguanidine↗