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Biomedical subjects

T Aburano

Publications and source records attributed to T Aburano.

At least 55 records · Page 3Linked to original sources

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↗

[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↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of hyperfunctioning parathyroid lesions in patients with hyperparathyroidism--a report of multicenter phase III clinical trials].

Phase III clinical study in 78 patients with hyperparathyroidism was performed to determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning parathyroid lesions. Except slight tremor in one patient, no adverse events were reported. No abnormal changes in clinical laboratories or vital signs were noted. The clinical utility of the agent was evaluated in 70 patients. Out of 108 hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of their histology, numbers, or location. Specifically, single or ectopic lesions were detected with high sensitivity (97% and 100%, respectively). Sensitivity in 53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is extremely high compared to the 201T1-99mTc subtraction method. Specificity in a group of PHP patients with single adenoma who underwent surgery was 100% (63/63), though in case of coexistent thyroid disease obviously interfered parathyroid images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of hyperfunctioning parathyroid tissues. Especially, the fact that 99mTc-MIBI detected ectopic glands with high specificity is a great advantage over the ultrasound or 201Tl-99mTc subtraction method.

Female↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of thyroid, breast and lung/mediastinum tumors--a report of multicenter phase III clinical trials].

Phase III clinical study in 136 patients diagnosed or strongly suspected of thyroid, lung/mediastinum or breast cancer was performed to determine clinical utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse events were reported. Seven abnormal changes in vital signs and 27 in clinical laboratories were noted, which were all judged as having no or unlikely relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3 were detected. Fifteen sites of false positive in 11 malignant tumor patients and 5 sites in 6 patients with non-tumor disease were observed. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of tumors. Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high sensitivity is a great advantage over the other conventional imaging modalities.

Adult↗

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↗

Therapeutic and imaging capacity of tumor-localizing radiosensitive Mn-porphyrin on SCCVII tumor-bearing C3H/He mice.

We synthesized a radiosensitizer KADTF, consisting of a hypoxic radiosensitizer, KU2280, bound to the side chain group of Mn-metalloporphyrin, which accumulates in tumor tissue. In the in vitro colony-forming activity test using HeLa cells, KADTF enhanced the effect of radiation under hypoxic conditions. Radiation therapy at 20 Gy, 1.5 h after infusion of KADTF (0.15 mM/kg), inhibited tumor growth more markedly than did a single radiation treatment. A clear tumor MR images of the SCCVII tumor was obtained at 1.5 h after administration of KADTF (0.1 mM/kg).

Animals↗

[Prognosis and MRI findings in patients with peripheral facial palsy].

We examined a series of 21 peripheral facial palsy patients attempted to (17 Bell's palsy, 4 Hunt syndrome) with Gd-DTPA-enhanced MRI and attempted to determine the relation between prognosis and MRI findings. We divided patients into two groups based on facial palsy scores of Japanese facial nerve research: a good group (G-Group) and a bad group (B-group). The G-group scored over 20 points on the 20th day after the first visit and the B-group under 20 points. G-group consisted of 9 Bell's palsy and 1 Hunt syndrome patients, and the B-group of 8 Bell's palsy and 3 Hunt syndrome patients. The averaged facial palsy score of both groups was analyzed every week during 4 weeks. Recovery from the palsy was better in the G-group than the B-group (P < 0.05); the scores at the 4th week of the G- and B-groups were 32.6 +/- 15.2 and 7.8 +/- 7.4, respectively. The MRI findings of both groups were examined retrospectively. Nine of 10 G-group and nine of 11 B-group patients had abnormal contrast enhancement. The result of enhanced facial nerve segment was as follows:G-group, auditory canal 1, labyrinthine/geniculate 7, tympanic 7, mastoid 7; B-group, auditory canal 2,labyrinthine/geniculate 8,tympanic 8, mastoid 7. Our results indicate no relation between the prognosis and the MRI findings. Therefore, it is impossible to predict the prognosis of facial palsy from the results of Gd-DTPA-enhanced MRI.

Adult↗

[Clinical significance of 123I-MIBG myocardial scintigraphy in patients with hypertrophic cardiomyopathy].

We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum 123I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of 123I-MIBG was significantly high respectively compared with normal subjects (n = 8). H/M was negatively correlated with serum norepinephrine level, wall thickness of left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, 123I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM.

3-Iodobenzylguanidine↗

[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↗

[Non-Hodgkin's lymphoma of stage I and II in elderly patients: a retrospective study in comparison with younger patients].

Forty-one patients with non-hodgkin's lymphoma at stages I and II who had received radiation therapy were reviewed to analyze the prognosis and prognostic factors, with the main focus on a comparison of elderly (age > 65 years) and younger patients. In terms of clinical and histological characteristics, there were no differences between the elderly and younger patients. The 5-year-survival rate (5YS) in elderly patients was 52.8%, compared with 68.6% for younger patients. In patients treated with irradiation alone, the 5YS was 49.5% in elderly patients and 22.1% in younger patients. Combination treatment consisting of irradiation and chemotherapy improved 5YS markedly to 84.9% in the younger patients, while no apparent improvement was seen in the elderly patients, in whom 5YS was 54.1%. Using Cox's multiregression life table, two prognostic factors, the presence of symptoms and LDH, were extracted and found to have a significant influence upon the survival of the elderly patients. Complete response was 90.2% in the elderly patients, although relapse was seen in 54.1% of the complete responders. Relapse occurred overwhelmingly outside the irradiated regions. Since the prognosis of elderly patients could not be improved with the current chemotherapy regimen, some different regimen must be established to lower the high relapse rate in the area outside the irradiated field.

Adolescent↗