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T Michigishi

Publications and source records attributed to T Michigishi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Combination radioimmunotherapy with local hyperthermia: increased delivery of radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts.

Hyperthermia (HT) may increase tumor targeting of a radiolabeled antibody by its effects on tumor vasculature and antigen expression. Expression of a 45-kDa glycoprotein antigen on LS180 colon cancer cells was 2.7-fold enhanced 2 days after heating at 43 degrees C for 1 h. Preferential tumor accumulation of 125I-A7 recognizing this antigen was doubled and the antitumor effect of 131I-A7 was significantly improved by HT. Hyperthermia also increased tumor uptake of an irrelevant antibody but its radioactivity was rapidly cleared. These results indicate that HT increased the initial delivery of an antibody to a tumor by its vascular effect, and radioactivity was retained in tumors by increased specific binding, resulting in a better radioimmunotherapy outcome.

Animals↗
PubMed1999

Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for clinical staging of chronic hepatocellular dysfunction.

Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human serum albumin (GSA) has been used for hepatocellular functional evaluation. This study proposed new and simple parameters to overcome the limitations of conventional parameters, and they were applied to the clinical staging of chronic liver dysfunction. The study group consisted of 93 patients including 81 with liver dysfunction and 12 control patients. In addition to the two conventional parameters, namely, receptor index (LHL15 = liver count divided by the sum of liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at 15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m GSA uptake and clearance were generated. The conventional receptor index of LHL15 showed a large variation depending on the size of region of interest (ROI) over the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data and a better separation of mild liver dysfunction. A hyperbolic relationship between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15 index. The combination of the liver to heart average count ratio at 15 minutes (LH 15) and T-half (minute) of the heart count also could differentiate each stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended instead of the conventional LHL15. The indices of LH15 and T-half could be alternatively used as practical parameters for clinical staging in liver function.

Adult↗
PubMed1999

Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts.

PURPOSE: The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated. METHODS: Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) (131)I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg(-1)day(-1) for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy. RESULTS: The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 +/- 9.59 days to 31.3 +/- 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU. CONCLUSION: The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

Animals↗
PubMed1999

Staging efficacy of breast cancer with sentinel lymphadenectomy.

Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologic findings in the nonsentinel nodes. The SLN was identified in 62 (88%) of 72 patients. Evaluation of the SLN on the permanent sections yielded a diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100%, although the reliability of SLN diagnosis using frozen sections or imprint cytology is limited. Therefore, it may be concluded that SLND with multiple sectioning and histopathologic examination of the SLNs can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, further studies will be needed to investigate the value of SLND in respect to the long-term regional control and any possible detriment or benefit to survival, before it can replace routine ALND as the preferred staging operation for operable breast cancer.

Adult↗
PubMed1999

Reversible cerebral hypoperfusion observed with Tc-99m HMPAO SPECT in reversible dementia caused by hypothyroidism.

A 69-year-old man had hypothyroid dementia as a result of I-131 therapy and an overdose of methimazole. Tc-99m HMPAO SPECT revealed diffuse cerebral hypoperfusion. The findings of brain SPECT normalized with the disappearance of symptoms and a return to the euthyroid state. There was a 25% or 26% reduction of the mean cerebral blood flow during dementia. This may be the first report in which SPECT brain imaging revealed reversible hypoperfusion associated with reversible hypothyroid dementia.

Aged↗
PubMed1999

Differential uptake of TI-201 by small-cell lung cancer in a patient with pneumoconiosis-related pulmonary nodules.

A 68-year-old man with pneumoconiosis was thought to have small-cell lung cancer based on the results of a biopsy of a bone tumor. Three pulmonary nodules were observed on a chest radiograph. Compared with a chest radiograph taken 4 months earlier, one of the nodules had grown. It was difficult to differentiate this nodule from pneumoconiosis-related benign pulmonary nodules from the appearance on the chest radiograph and CT. Ga-67 scintigraphy and TI-201 lung SPECT were performed to characterize these nodules. TI-201 SPECT showed differential high uptake in the enlarged nodule, whereas Ga-67 scintigraphy showed equally intense uptake in all these nodules. Transbronchial biopsy of the nodule that showed high TI-201 uptake revealed cancer cell nests against a background of interstitial fibrosis. The pathologic diagnosis was small-cell lung cancer that had developed in lung scar tissue. This case suggests the utility of TI-201 in scintigraphic assessments of pneumoconiosis-related pulmonary nodules when lung cancer is suspected.

Aged↗
PubMed1999

Early response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201Tl-chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin in human bladder cancer cells and human leukocytes.

The uptake and retention of single photon tracers in irradiated tumour cells was observed in an attempt at the early evaluation of the effect of radiation. T24 human bladder cancer cells were exposed to a single dose of 10 Gy or 20 Gy or a fractionated dose of 10 Gy (2 Gy for 5 days). The uptake of 201Tl chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin was observed by incubating in vitro for 60 min. The retention of the tracers was observed at 60 min after changing the incubation medium for a tracer-free medium. Uptake per culture well of all tracers in the cells exposed to 20 Gy declined as viable cell number decreased, but uptake per cell increased progressively. Uptake per cell of all tracers in the cells exposed to either a single dose or a fractionated dose of 10 Gy also increased, while a delay in growth was observed. The retention of these tracers decreased during this period and recovered thereafter. A binding assay with purified human leukocytes indicated that assessment with 99Tcm-sestamibi and 99Tcm-tetrofosmin is influenced by inflammatory cells. In conclusion, the effect of radiation may be underestimated if assessed by tracer uptake alone because of the increase in tracer uptake in viable irradiated cells. Observation of the retention of tracers may provide additional information.

Humans↗
PubMed1999

Preoperative assessment of residual hepatic functional reserve using 99mTc-DTPA-galactosyl-human serum albumin dynamic SPECT.

UNLABELLED: Preoperative assessment of residual hepatic functional reserve offers important strategic information for hepatic resection. To predict the postoperative residual liver function, we assessed the value of hepatic 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) clearance estimated by dynamic SPECT analysis. METHODS: We investigated 114 consecutive patients with liver disease, including 55 hepatectomy cases. One minute after injection of 185 MBq 99mTc-GSA, 15 serial dynamic SPECT images were obtained every minute. The initial five sets of SPECT images were analyzed by Patlak plot to estimate the sequential initial hepatic 99mTc-GSA clearance (mL/min) as an index of hepatic function. The sum of hepatic 99mTc-GSA clearance of the segments immune from resection was categorized as predicted residual 99mTC-GSA clearance. In the hepatectomy cases, scintigraphy was performed before and 37 +/- 10 d after the operation. RESULTS: Good correlation was observed between the total hepatic 99mTc-GSA clearance and conventional hepatic function tests: plasma retention rate of iodocyanine green (ICG) at 15 min (ICG R15), r = -0.600, P < 0.0001, n = 94; plasma disappearance rate of ICG (K ICG), r = 0.670, P < 0.0001, n = 83; cholinesterase, r = 0.539, P < 0.0001, n = 121; serum albumin, r = 0.421, P = 0.0001, n = 123; and hepaplastin test, r = 0.456, P < 0.0001, n = 120. There was good correlation between the predicted residual 99mTc-GSA clearance and the postoperative total hepatic 99mTc-GSA clearance in patients who underwent segmentectomy or lobectomy (r = 0.84, P < 0.0001, n = 28) and between the pre- and postoperative total hepatic 99mTc-GSA clearance in patients who underwent subsegmentectomy (r = 0.91, P < 0.0001, n = 25). Five patients who had postoperative complications due to hepatic insufficiency (2 patients died of postoperative hepatic failure within 2 mo after operation) showed significantly lower predicted residual 99mTc-GSA clearance compared with the patients without complications (90.3 +/- 37.2 versus 320.9 +/- 158.8 mL/min; P < 0.005). CONCLUSION: The total hepatic 99mTC-GSA clearance reflected hepatic function. In addition, preoperative predicted residual hepatic 99mTc-GSA clearance was a good indicator of postoperative hepatic function and early prognosis. 99mTc-GSA dynamic SPECT is assumed to be a useful method for determining the surgical strategy in patients with hepatic tumor and especially in patients with hepatic dysfunction.

Coloring Agents↗
PubMed1998

Superiority of triple-detector single-photon emission tomography over single- and dual-detector systems in the minimization of motion artefacts.

A patient motion-related artefact is one of the most important artefacts in single-photon emission tomography (SPET) imaging. This study evaluated the effect of the number and configuration of SPET detectors on motion artefacts. The following acquisition conditions were simulated based on original 360 degrees projection images: (1) single-detector 180 degrees rotation (S180), (2) a dual-detector rectangular (L-shaped) 180 degrees acquisition (D180L), (3) dual-detector cameras mounted opposite each other with 360 degrees acquisition (D360) and (4) triple-detector 360 degrees acquisition (T360). The motion artefacts were introduced using a syringe and a myocardial phantom. Clinical cases with technetium-99m methoxyisobutylisonitrile and thallium-201 studies were analysed to confirm the validity of this phantom simulation. The effect of continuous alternate rotation acquisition and summing the projections on the reduction of motion artefacts was investigated in each model. The effect of motion depended on the number and the configuration of the SPET detectors. A 1-pixel (6.4 mm) motion in the S180, D180L and D360 models generated only slight artefacts, and a 2-pixel motion led to an apparent decrease in activity or created hot areas in the myocardium. On the other hand, a T360 rotation created few artefacts even with a 2-pixel motion of the last quarter of the projections. Despite the difference in attenuation with 201Tl and 99mTc, similar artefact patterns were observed with both radionuclides in selected patient model studies. Continuous alternate rotation could reduce artefacts caused by less than a 2-pixel motion. In conclusion, calculating the average of the sum of the projections of triple-detector 360 degrees rotations with alternate rotation is the best method to minimize motion artefacts. This "averaging" effect of motion artefacts is a key to this simulation.

Gamma Cameras↗
PubMed1998

Effect of 360 degrees and 180 degrees rotation SPET acquisitions on myocardial polar map: comparison of 201Tl-, 99Tcm- and 123I-labelled radiopharmaceuticals.

Both 360 degrees and 180 degrees rotation acquisition methods have been used in myocardial single photon emission tomography (SPET) studies. We compared both methods using 201Tl, 99Tcm and 123I radiopharmaceuticals with phantoms and clinical models. Myocardial phantom studies with anterior and inferior defects were performed using 201Tl, 99Tcm and 123I. Clinical models of 14 typical situations, including normal subjects, patients with anterior or inferior defects and a high right hemi-diaphragm, were studied. The radiopharmaceuticals were 201Tl, 99Tcm-sestamibi, 123I-BMIPP and 123I-MIBG. Four sets of 180 degrees anterior rotation data with starting angles of (A) posterior, (B) LPO 30 degrees, (C) LPO 60 degrees and (D) left lateral direction were generated and compared with 360 degrees rotation SPET. A polar map display was used for quantification. In phantom studies, the defect contrast on the map was higher in the anterior defect with 180 degrees rotation than with 360 degrees rotation. However, it was decreased in the inferior defect, particularly with 201Tl, because of decreased wall activity around the defect. In the patient model with anterior or inferior defects, the defect contrast was improved with 180 degrees SPET by up to 10%. A slight decrease in the normal region was also noted in the 180 degrees reconstruction. The effect of diffuse liver activity on the inferior region depended on the rotation range. A patient with a high right hemi-diaphragm showed a lower inferior count with 360 degrees SPET. In conclusion, the 360 degrees acquisition was superior to the 180 degrees acquisition in the phantom with defects. Clinically, the quantitative differences in radionuclide types (99Tcm, 123I or 201Tl) were not significant for quantifying a moderate degree (50-60% of peak count) of defect. However, we note quantitative variation depending on the rotation range in the 180 degrees method.

3-Iodobenzylguanidine↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

The Role of Axillary Lymph Node Dissection in Breast Cancer Management.

Although it is generally accepted that axillary dissection provides no survival advantage in patients with breast cancer, it is commonly regarded as a reliable method of assessing nodal status and treating regional disease. However, it is time to consider eliminating routine axillary dissection in patients who are clinically node-negative. A sentinel lymph node biopsy may assess axillary nodal status while obviating a full axillary dissection. At present, axillary dissection remains the standard approach for the surgical management of all patients with invasive carcinoma of the breast, regardless of tumor size or patient age, though it is unnecessary for patients with small intraductal carcinomas.

Journal Article↗
PubMed1997

Intense Ga-67 uptake in adenosquamous carcinoma of the pancreas.

Gallium-67 citrate (Ga-67) scintigraphy was performed in a patient with adenosquamous carcinoma of the pancreas. Intense and homogeneous uptake was observed in the tumor. Few reports have dealt with Ga-67 findings in pancreatic cancers. Ga-67 uptake in the tumor was assumed to be due to accumulation in the component of squamous cell carcinoma. This case suggested that Ga-67 citrate scintigraphy may be useful in detecting adenosquamous carcinoma of the pancreas. To our knowledge, no report has described findings of Ga-67 citrate scintigraphy of adenosquamous carcinoma of the pancreas. Radiologists should remember adenosquamous carcinoma of the pancreas when encountering such scintigraphic findings.

Aged↗
PubMed1997

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↗