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Biomedical subjects

N Oriuchi

Publications and source records attributed to N Oriuchi.

At least 55 records · Page 3Linked to original sources
PubMed1999

In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26.

AIM: The purpose of this study was to assess the potential for radio-immunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. METHODS: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. RESULTS: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 +/- 0.95% vs. 11.9 +/- 0.55% at 100 ng/mL of soluble CEA, 83.5 +/- 2.84% vs. 54.0 +/- 2.54% at 10(7) of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 +/- 3.50% ID/g vs. 14.4 +/- 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 +/- 2.10% ID/g vs. 8.01 +/- 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 +/- 1.70% ID/g vs. 8.10 +/- 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). CONCLUSION: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

Adenocarcinoma↗
PubMed1999

[Immunoscintigraphy and radioimmunotherapy of cancer using monoclonal antibodies].

Technologies using radiolabeled antibodies have advanced significantly over the past decade, although radioimmunotherapy still requires improvements. This paper describes the implications of nuclear medicine in the management of cancer in terms of detection, staging, and qualification of patients for immunotherapy. The results of a clinical trial performed at our institution using 99mTc-labeled anti-CEA monoclonal antibody are briefly reviewed. Immunoscintigraphy has shown particular promise as a means of whole body imaging in patients with colorectal, breast, or lung cancer, and the antibodies used for diagnostic imaging are now being used for radioimmunotherapy. Radioimmunotherapy of B-cell lymphoma has been successfully performed using 131I or 90Y labeled anti-lymphocyte monoclonal antibodies, although the treatment of solid tumors is still a major difficulty. Elimination of the immune response by generating humanized monoclonal antibodies, which are virtually devoid of immunogenicity, is necessary to allow repeated administration. This is especially true of patients with solid tumors as compared with patients with hematopoietic ones.

Antibodies, Monoclonal↗
PubMed1998

Assessment of malignancy of glioma by positron emission tomography with 18F-fluorodeoxyglucose and single photon emission computed tomography with thallium-201 chloride.

The histological diagnosis and proliferative potential measured by bromodeoxyuridine (BrdU) labelling index (LI) were correlated with preoperative CT and contrast-enhanced, MRI, 18F-fluorodeoxyglucose positron emission tomography (PET) and 201T1 single photon emission computed tomography (SPECT) in 43 patients with various grades of glioma. 201T1 SPECT had slightly higher sensitivity to tumours with BrdU LI > or = 5% (showing 10/10) than 18F-FDG PET (7/8 tumours). 18F-FDG PET was better for identifying tumours of BrdU LI < 1% (13/15) than 201T1 SPECT (13/22). Accumulation of 201T1 in the tumour was slightly different from contrast enhancement on CT and/or MRI, and gave "false-positive" results in some low-grade gliomas. However, 201T1 SPECT, which is available in many hospitals and may cost less, provided useful information to supplement that from CT and MRI.

Astrocytoma↗
PubMed1998

Role of indium-111 labelled platelet scintigraphy in the management of thrombocytopenic patients with malignant neoplasms.

This study was done to investigate the role of indium-111 labelled platelet scintigraphy in the treatment of thrombocytopenia in patients with malignant neoplasms. The study involved 20 consecutive patients with thrombocytopenia associated with malignant neoplasms of hematological disorders and without evidence of underproduction of megakaryocytes due to chemotherapy or bone marrow infiltration by the malignancy. Splenic sequestration of platelets was evaluated by measuring splenic uptake of 111In-labelled platelets, and findings were correlated with the outcome of splenectomy and medication. Of the 20 patients, 13 had splenic sequestration of platelets. Seven of the 13 patients underwent splenectomy; six of these seven patients experienced a complete response. The other six patients received medication only and showed no response. Of the seven patients without splenic sequestration of platelets, five received medication, and four of them responded to it. 111In-labelled platelet scintigraphy has a role in selecting appropriate therapy and predicting its efficacy in patients with thrombocytopenia associated with malignant neoplasms.

Adult↗
PubMed1998

Antibody-dependent difference in biodistribution of monoclonal antibodies in animal models and humans.

The study was designed to clarify the difference in pharmacokinetics of monoclonal antibodies (mAb) in animal models and humans, and to elucidate the applicability of animal models. 99mTc-labeled murine mAb -- against carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule (NE150) -- and one chimeric mouse/human mAb against nonspecific cross-reacting antigen (chNCA) were administered i.v. to normal mice and athymic mice (370 kBq, 400 ng) xenografted with human cancer cells expressing antigens, and into patients with tumor (925 MBq, 1 mg). The biodistribution of two of the three mAb (not 99mTc-BW431/26) differed clearly in mice and patients. 99mTc-NE150 showed specific uptake in xenografted tumor and otherwise a normal biodistribution; however, clinical examination showed increased uptake in the liver with rapid blood clearance (mean alpha half-life = 31.1 min) compared with 99mTc-BW431/26 (28.4 h). 99mTc-chNCA demonstrated increased blood clearance and renal excretion in both normal and athymic mice, with accumulation in tumors. Clinical examination showed rapid blood clearance (mean alpha half-life = 6.4 min) and increased uptake in the liver. High-performance liquid chromatographic analysis of 99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the complex by the reticuloendothelial cells. The biodistribution of radiolabeled mAb in animal and human models was variable and specific for each of the three mAb. The results of animal studies with mAb should be evaluated carefully before being extrapolated to humans, on the basis of the nature of the mAb and interacting substances.

Animals↗
PubMed1998

High predictive value of red cell volume measurement using carboxy-haemoglobin in a rabbit model of haemorrhage.

We have studied the accuracy of blood volume measurements using carbon monoxide (CO)-labelled haemoglobin (COHb) injection and dilution (CO method) by comparing changes in red cell volume (RCV) measured using the CO method and 51Cr-labelled erythrocyte dilution (51Cr method) in a haemorrhage and infusion model in rabbits. RCV was measured repeatedly using the CO method at four different blood volume stages (stages I-IV). At stages I and IV, RCV was measured simultaneously using the 51Cr method. In comparing the sum of the circulating RCV and extracted RCV (SUM RCV) using the CO method, the values were almost equal and there were no significant differences between the values at the four stages. In comparing circulating RCV measured using the CO method and the 51Cr method, mean difference between the two methods was 0.80 (SD 0.76) ml kg-1 or 4.7 (4.6)%, and a positive correlation was observed (r = 0.91). We conclude that the CO method can be used to measure blood volume during perioperative periods in infants because it avoids use of a radioactive tracer, is simple and repeated measurements are possible.

Animals↗
PubMed1998

In vitro effect of contrast agents during immunoradiometric assay for tumour-associated antigens.

The aim of this study was to investigate if contrast agents interfere with the performance of an immunoradiometric assay (IRMA) in vitro for serum tumour-associated antigen. Each of five carcinoembryonic antigen (CEA)-positive sera, CA-130-positive sera and tissue polypeptide antigen (TPA)-positive sera was mixed with six contrast agents: Ioversol 350, Iopamidol 370, Iomeprol 300, Iomeprol 400, Iohexol 300 and Gadopenteic acid in 50:50, 50:20, 50:5.0, 50:1.0, 50:0.5 and 50:0.1 microl proportions. Following IRMA, the interference of binding rates in each mixture was calculated, and the serum concentrations of CEA, CA-130 and TPA were estimated and compared with the originals. All contrast agents used were able to inhibit the binding rate with IRMA and the inhibition rates were in proportion to the amount of contrast agent. The detection of serum concentrations of CEA, CA-130 and TPA was significantly inhibited in the mixtures with more than 5.0 microl of contrast agent in all cases. Apart from Iomeprol 400, there was no significant inhibition of detection at the lowest concentrations of contrast agents. Iomeprol 400 was the strongest inhibitor and Gadopenteic acid the weakest inhibitor for each IRMA of the contrast agents employed. In conclusion, our results demonstrate that contrast agents may reduce the immunoreaction of antibody and antigen and lead to in vitro inhibition during immunoassays. It would be unwise to perform any plasma/serum immunoassay on a sample collected within 24 h of the administration of contrast agent considering the pharmacokinetics.

Aged↗
PubMed1998

99Tcm-labelled chimeric human/mouse anti-granulocyte antibody bone marrow scintigraphy: a preliminary clinical study.

Bone marrow scintigraphy using 99Tcm-labelled chimeric anti-granulocyte antibody (anti-NCA-95) was performed in 17 patients with haematological disorders and skeletal metastases. Chimeric anti-NCA-95 antibody (chNCA95 Ab, 0.2 mg) labelled with 444 MBq 99Tcm was administered to obtain bone marrow images 4 h post-injection. One week later, an 111In-chloride bone marrow scan was performed on nine patients with haematological disorders. Lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B) uptake ratios were calculated for each scan. In six patients with suspected skeletal metastases, 99Tcm-HMDP bone scans were performed. No patient had any adverse reaction or any immune reaction over 20 weeks. In the patients with haematological disorders, the L/B and I/B ratios of the 99Tcm-chNCA95 Ab scan were 3.41 +/- 0.90 and 1.23 +/- 0.31, whereas those of the 111In-chloride scan were 1.58 +/- 0.32 and 1.00 +/- 0.32, respectively. In assessing findings of irregular central bone marrow uptake and peripheral expansion of the bone marrow, the 99Tcm-chNCA95 Ab scan was much better than the 111In-chloride scan. In the six patients with suspected skeletal bone metastases, three true-positive and two true-negative results were observed. This preliminary study has revealed that 99Tcm-chNCA95 Ab scanning is safe and useful in the diagnosis of haematological disorders and skeletal metastases.

Adult↗
PubMed1998

Semi-automated renal region of interest selection method using the double-threshold technique: inter-operator variability in quantitating 99mTc-MAG3 renal uptake.

In calculating the relative and absolute renal uptake of technetium-99m mercaptoacetyltriglycine (MAG3), inter-operator variability in the assignment of the renal region of interest (ROI) is a critical factor. Our goal was to develop a semi-automated method of assigning the renal ROI and then to compare the inter-operator variability in calculating the percent injected dose (%ID) in the kidney at 1-2 min, using semi-automated versus manual ROIs. The manual ROIs were drawn independently by three operators (A, B and C). Operator A had about 20 years, experience in nuclear medicine, while operators B and C respectively had 3 years and 1 year of experience. In the semi-automated renal ROI selection method using the double-threshold technique, the operators only click around the centre of each kidney. The same three operators processed the ROIs using this double-threshold method on 1-2 min images. The semi-automated method failed in three kidneys with very markedly reduced function owing to superimposition by liver or spleen. Inter-operator reproducibility in the remaining 59 kidneys was estimated using manual and semi-automated ROIs. With manual ROIs, the %ID (mean+/-standard error of mean) was 4.32+/-0.167 for A, 4. 14+/-0.165 for B and 3.28+/-0.139 for C. Although there was good correlation among them, these values were significantly different (P<0.0001). Using semi-automated ROIs, the %ID was 4.38+/-0.160 for three operators. No significant difference was observed. Complete reproducibility was shown in 58 of 59 kidneys; the %ID difference of the remaining kidney was only 1.2%. The lowest %ID of all the kidneys successfully detected using the semi-automated method was 0. 77%. The semi-automated renal ROI selection method using the double-threshold technique displays good detectability of the renal contour. The renal uptake calculated using this method is reproducible and acceptable in routine clinical practice.

Adolescent↗
PubMed1998

Noninvasive measurement of renal function with 99mTc-MAG3 gamma-camera renography based on the one-compartment model.

OBJECTIVE: The aim of this study was to develop a method for measuring renal function with 99mTc-MAG3 gamma-camera renography without blood or urine sampling and evaluate its feasibility. PATIENTS, MATERIAL AND METHODS: Twelve patients with nephrological disorders underwent 99mTc-MAG3 renography and para-aminohippurate clearance measurement. Plasma clearance of 99mTc-MAG3 (ClMAG) was calculated through early renal uptake of 99mTc-MAG3 after appropriate correction of parameters (background, measured attenuation coefficient of 99mTc, and the actual depth of kidneys measured with computed tomography), and on one-compartment assumption of the kinetics of 99mTc-MAG3. We compared the resultant ClMAG with standard effective renal plasma flow (ERPF), using the para-aminohippurate clearance method and with simulated ClMAG derived from the two-compartment model. RESULTS: ClMAG calculated by the one-compartment model (283+/-131 ml/min, mean +/- SD) correlated with ERPF (r = 0.94, p <0.001), and was similar to the simulated ClMAG estimated from the two-compartment model in all patients (283+/-139 ml/min). CONCLUSION: This alternative method, which employs theoretical modeling of the pharmacokinetics of 99mTc-MAG3, may provide easy, noninvasive measurement of individual renal function without blood sampling or in vitro equipment. Further studies should be warranted.

Computer Simulation↗
PubMed1997

Preparation of yttrium-90-labeled human macroaggregated albumin for regional radiotherapy.

Human macroaggregated albumin (MAA), which is currently labeled with technetium-99m (99mTc) and 99mTc-MAA, is used clinically as a pulmonary perfusion agent and was directly labeled with yttrium-90 (90Y)-acetate. This study evaluated whether 90Y-MAA could be potential radiotherapeutic agent for regional radiotherapy against malignant tumors. MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 90Y-acetate and purified in order to get rid of unstable binding of 90Y by electrophoresis. The radiochemical purity of 90Y-MAA in normal human serum was estimated by an agarose electrophoresis method and was more than 94% over 168 h in vitro. Following the intratumoral administration of 90Y-MAA, the time course of tumor radioactivity and the biodistribution in nude mice bearing human neuroblastoma were investigated up to 168 h. More than 93% of the radioactivity of the injected dose was found on the subcutaneous tumor over 168 h. The bone radioactivity was shown as 0.06 +/- 0.03% injection dose/gram tissue (% ID/g) (n = 5) at 24 h, 0.73 +/- 0.20% ID/g at 72 h, 0.92 +/- 0.16% ID/g at 120 h, and 2.51 +/- 0.59% ID/g at 168 h. A slight increase in radioactivity was noted in the liver, kidneys, and spleen over the 168-h periods. In conclusion, 90Y-MAA may be a potential agent for regional radiotherapy (brachytherapy) because of the sufficient persistence in the tumor following an intratumoral administration.

Albumins↗
PubMed1997

99Tcm-MAG3: a sensitive indicator for evaluating perfusion and rejection of renal transplants.

Radionuclide renography has a role in evaluating perfusion of transplanted kidneys. In the course of rejection, cortical perfusion decreases before urinary excretion changes. Based on the facts that 99Tcm-MAG3 has different pharmacokinetics and shows a higher kidney-to-background count ratio than 99Tcm-DTPA, we postulated that 99Tcm-MAG3 was a sensitive and reproducible agent to measure cortical perfusion of transplanted kidneys. To clarify the feasibility of using 99Tcm-MAG3 to measure the cortical perfusion index (CPI), sequential renography was performed using 99Tcm-DTPA and 99Tcm-MAG3 in 14 patients with stable renal transplants, who had changes in serum creatinine concentration of less than 50% between the two studies. The CPI was calculated with 99Tcm-DTPA and 99Tcm-MAG3 and these were then compared and correlated with concurrent serum creatinine concentration. The CPI with 99Tcm-MAG3 was 1.43 times that with 99Tcm-DTPA in patients with changes in serum creatinine concentration equal to or less than 20%, and regression analysis revealed that the difference in CPI was larger in patients with more severely decreased renal perfusion than in patients with normal or mildly decreased renal perfusion. This preliminary study has indicated that the CPI with 99Tcm-MAG3 is a sensitive index for detecting changes in renal function, and thus is a feasible indicator of cortical perfusion when evaluating the rejection of transplanted kidneys.

Adult↗
PubMed1997

Direct labeling of macroaggregated albumin with indium-111-chloride using acetate buffer.

UNLABELLED: Indium-111-labeled macroaggregated albumin (MAA) would be suitable for combined pulmonary perfusion and ventilation scan using a 99mTc ventilation agent. METHODS: MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 111In-chloride for 30 min at room temperature. An in vitro study of the obtained 111In-MAA was performed for labeling efficiency and stability in human normal serum. The 111In-MAA was intravenously injected into normal mice, and the biodistribution was studied at 15 and 180 min postinjection. A gamma camera image was obtained at 15 min after injection. RESULTS: MAA was directly and stably labeled with 111In-chloride, and the labeling efficiency of the preparation was more than 96%. More than 90% of the administered 111In-MAA was caught in the murine lung. The scintigraphy with 111In-MAA showed a clearly visualized murine lung. CONCLUSION: Indium-111-MAA can be conveniently prepared by direct labeling at room temperature. It provides an alternative perfusion tracer for combined perfusion-ventilation imaging.

Animals↗
PubMed1997

Isolated limb perfusion in the sarcoma-bearing rat: a novel preclinical gene delivery system.

Reliable site-specific delivery of genetic constructs remains a challenging component of gene-based therapy of solid tumors. Isolated limb perfusion (ILP) continues to be evaluated for treatment of locally advanced soft tissue sarcomas because this approach uniquely directs therapeutic agents into the tumor-bearing extremity without significant systemic leak. In light of these considerations, we tested the hypothesis that ILP could be used to deliver genes carried in viral vectors to the sarcoma-bearing rat extremity, resulting in demonstrable gene transfer into the tumor. ILP was performed in rats by cannulating the femoral artery and vein, isolating the hind limb from systemic circulation by tourniquet, and cycling perfusate for 15 min at a rate of 2.4 ml/min. Leakage into the systemic circulation was 7.5% of the total perfusate concentrated in the isolated limb, as determined by perfusion with technetium 99m-tagged RBCs. We used the ILP technique to perfuse rat hind limbs bearing syngeneic fibrosarcoma tumor nodules with the replication-defective adenovirus Ad5LacZ, which expresses the bacterial beta-galactosidase. 5-Bromo-4-chloro-3-indolyl-beta-D-galactoside staining of the perfused limb tissues confirmed gene transfer to the tumor and peritumoral tissue, demonstrating that the tumor was part of the perfusion circuit and that gene therapy delivered via this method was feasible. These results suggest that adaptation of this preclinical gene delivery model to administer genetic constructs aimed at controlling tumor growth may prove beneficial to patients with extremity sarcomas.

Adenoviruses, Human↗