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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 253 records · Page 14Linked to original sources

[Immunoscintigraphy of colorectal cancer with 111In labeled anti-CEA monoclonal antibody (ZCE-025)].

Clinical trials with 111In labeled anti-CEA monoclonal antibody (ZCE-025) was initiated. Five patients with colorectal cancer suspected were given an intravenous injection of 1 mg of 111In labeled ZCE-025. Planar and SPECT images were obtained 24 and 72 hours after injection. Surgical operation was performed on all patients between 7 and 10 days post injection. Of 4 primary sites, all were clearly visualized. Intrahepatic metastasis was visualized as higher activity than normal liver in one of two patients. In one patient whose imaging was negative, no residual cancer was found at surgery. Persistent accumulation of 111In in the lymph nodes was also observed in one patient. Surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon cancer. No side effects were encountered, although HAMA were detected in all 5 patients by 4 weeks after the administration of ZCE-025. Immunoscintigraphy appears useful in distinguishing recurrent tumor from postoperative granuloma. Further investigation directed to the causes of 111In accumulation in tumor-free lymph nodes is required.

Aged↗

[Clinical evaluation of 99mTc-hexakis 2-methoxy isobutyl isonitrile (MIBI): multicenter phase III clinical trial].

Multicenter Phase III clinical trial on a new myocardial imaging agent, 99mTc-hexakis 2-methoxy isobutyl isonitrile (99mTc-MIBI), was carried out in 464 patients with various cardiac disorders. Both planar and tomographic images provided high-quality regional myocardial perfusion images which correlated well with 201TlCl images. The positive ratios of myocardial infarction and angina pectoris by the agent were as high as that of 201TlCl. In addition, ventricular function and wall motion could be assessed with first-pass and ECG gated studies. There was no serious adverse reaction which were attributed to 99mTc-MIBI in any of patients studied. A transient metallic taste was observed immediately after the injection in approximately 64% of the patients. Based on its safety and efficacy, the clinical usefulness of 99mTc-MIBI was observed in 562 (93.1%) of 604 injections. In conclusion, 99mTc-MIBI was useful as a imaging agent of myocardial blood flow.

Adolescent↗

[Phase I clinical study on 99mTc-MIBI].

A phase I clinical study on 99mTc-hexakis 2-methoxy isobutylisonitrile (99mTc-MIBI) was carried out in 6 normal volunteers. There was no significant change in vital signs and laboratory parameters attributing to the reagent other than complaint of slight and transient metallic taste immediately after the injection in 4 volunteers. The highest dosimetry was calculated as 1.1 mGy/37 MBq at lower large intestine, which was within the acceptable range. 99mTc-MIBI was rapidly cleared from the blood and accumulated in the heart immediately after the injection with 1.4% dose and 1.8% dose at 5 min at rest and at stress, respectively. The retention of radioactivity in the heart well continued for at least several hours. The heart-to-lung ratio was over 2.00 at 5 min and heart-to-liver ratio was over 1.00 at 60 min. Myocardial planar and SPECT images were obtained with high quality. In conclusion, 99mTc-MIBI is a useful myocardial perfusion imaging agent.

Adult↗

[Pulmonary inhalation scintigraphy using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) aerosol].

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) is lipophilic substance and permeates through the alveolar epithelium via intracellular transport, whereas 99mTc-DTPA is water-soluble substance and permeates through the alveolar epithelium via paracellular transport. We performed inhalation lung imaging using 123I-IMP and 99mTc-DTPA in order to assess alveolar epithelial permeability in 4 patients with restrictive ventilatory impairment, and 5 volunteers including one smoker. The time-activity (T/A) curves of 123I-IMP were well fitted into two compartments, first and slow, by least-squares fit technique, in contrast to 99mTc-DTPA fitted well with one compartment. In 4 normal volunteers, the T/A curves of the lower pulmonary fields declined faster than those of other pulmonary fields. In 99mTc-DTPA studies, the Kep values of patients with restrictive ventilatory impairment (n = 4) were higher than those of normal volunteers (n = 4) (2.14 +/- 0.30 x 10(-4) vs 1.48 +/- 0.41 x 10(-4), p less than 0.005). On the other hand, in 123I-IMP studies, the Kep values of the patients were much lower than those of normal volunteers (6.79 +/- 0.55 x 10(-5) vs 1.52 +/- 0.45 x 10(-3), p less than 0.005).

Administration, Inhalation↗

A toxic substance produced by Nocardia otitidiscaviarum isolated from cutaneous nocardiosis.

During our studies on toxic substances from clinically isolated Nocarida, a new isolate identified as Nocardia otitidiscaviarum from cutaneous nocardiosis was found to produce a toxic substance called HS-6 that had strong in vitro as well as in vivo toxicity. The mouse intraperitoneal LD50 value was 1.25 mg/kg and the ED50 value for L1210 cultured cells was 0.3 ng/ml. The structure of HS-6 was determined and found to belong to the 16-membered macrocyclic group with a molecular formula of C43H68O12. HS-6 also showed activity against pathogenic fungi such as Cryptococcus neoformans.

Aged↗

Bone scanning in patients with pleural effusion--experience in 76 cases.

Seventy-six patients with malignant or benign pleural effusion were studied to determine the incidence of accumulation of 99mTc-MDP in relation to effusion, and reveal the mechanism. Of 76 patients, 46 (61%) were found to have diffuse uptake of 99mTc-MDP in the hemithorax, with almost the same positive rate in malignant and benign effusions, i.e. 62% and 57%, respectively. Of 46 patients, 32 (70%) showed diffuse, slight accumulation in the hemithorax, and the positive rate had a tendency to be higher with the increase in the effusion volume. We are convinced that the major mechanism of unilateral intrathoracic accumulation of 99mTc-MDP in pleural effusion is a passive transudation.

Adult↗

Effects of circulating antigen on monoclonal antibody localization.

The potential effects of free circulating antigen on the ability of monoclonal antibodies to target tumors in vivo were investigated. Tumor models consisted of HCC, NuE and PLC cell lines producing AFP xenografted in nude mice, and the NuE-treated mouse designated as the NuE-bearing mouse injected with AFP prior to the administration of antibody. Immunoscintigraphy and biodistribution were evaluated by using 125I-labeled monoclonal antibody 19F12 raised against AFP. Gel chromatography analysis of plasma from the PLC-bearing mouse which excreted 400 ng AFP/ml in blood injected with 125I-19F12 indicated that all injected antibody 19F12 formed an immune complex in plasma. No immune complex was present in plasma from the NuE-bearing mice, where blood AFP levels were 7 ng/ml, while the intact antibody was found to remain partly in plasma from the NuE-treated mouse. Radioactivities in the whole body of NuE-bearing and NuE-treated mice eventually cleared at the same rate. Our experimental results indicated that the endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also by how rapid the antigen was cleared in the blood.

Animals↗

[A phase III multi-center clinical trial on 123I-orthoiodohippurate (123I-OIH)].

A multi-center clinical trial was performed to evaluate the clinical usefulness of 123I-orthoiodohippurate (123I-OIH) in patients with renal and urinary disorders. 123I-OIH was evaluated to be "safe" in all 259 cases it was injected. 123I-OIH was useful in all 248 cases analyzed for the overall clinical usefulness evaluated by the investigators. The clinical significance of the drug was also evaluated in terms of renal blood flow function, renal parenchymal function, urinary function and the ability to differentiate between renal and urinary disorders. In the comparison with 123I-OIH (90 cases), 123I-OIH was superior as evaluated by the investigators and the Committee both. In the comparison with 99mTc-DTPA (113 cases), 123I-OIH was evaluated as superior by the investigators, but no significant difference was found by the Committee. In image qualities, 123I-OIH was evaluated as superior to 131I-OIH and equal to 99mTc-DTPA by the Committee. In overall efficiency, 123I-OIH was evaluated as being more valuable than 131I-OIH in 92% of the 90 cases and more valuable than 99mTc-DTPA in 50% of the 113 cases. 123I-OIH was evaluated as being less valuable than 131I-OIH in no cases and less valuable than 99mTc-DTPA in 7% of the 113 cases. These results suggest that 123I-OIH is superior to 131I-OIH and equal or superior to 99mTc-DTPA as a radiopharmaceutical for gamma camera-renography.

Clinical Trials as Topic↗

[Experimental study on liver accumulation of N-isopropyl-p-iodoamphetamine].

In order to clarify the mechanism of N-isopropyl-p-iodoamphetamine (IMP) liver accumulations, liver dynamic study by the portal injection of 123I-IMP and liver microautoradiography by 125I-IMP were performed using 5, 2 male rats, respectively. The initial uptake of 123I-IMP in the liver was very high and thereafter 123I-IMP showed relatively rapid wash-out (count ratio of lung to liver at 10 min after the injection was 0.12, 0.15). On the other hand, the addition of 5 mg, 8 mg ketamine hydrochloride decreased the initial 123I-IMP liver uptake and its lung accumulation was noted immediately after the injection (count ratio of lung to liver at 10 min was 0.20). Microautoradiography of the liver using 125I-IMP showed grain density in the central vein and sinusoids, but not in the liver parenchymal cell. These results suggest that non-specific amine receptor (binding site) may exist in the endothelial cell in the central vein, although the number of experimental rats in this series was small for conclusion.

Amphetamines↗

[Experimental study on N-isopropyl-p-iodoamphetamine lung uptake].

Experimental study on N-isopropyl-p-iodoamphetamine lung uptake was performed by means of analyzing microautoradiography obtained by administering 125I-IMP to Wistar male rats. In the normal rat lung at one minute after the intravenous injection of 125I-IMP, there is increased grain density in the interstitial space including the capillary lumen and interalveolar septum, but not in the alveolar space. On the other hand, at 24 hours after the intravenous injection, increased grain density was noted in the alveolar space of the rat lungs which had received a dose of 10 Gy to the unilateral one. But, definite difference was not found in grain density between the irradiated and non-irradiated lung. The results indicate that part of IMP which was taken up by the endothelial cell is capable of passing through capillary-alveolar barrier.

Amphetamines↗

[Tumor imaging using 99mTc-hexamethylpropyleneamine oxime].

Tumor imagings have been performed in 32 tumor sites in 28 patients with a variety of malignancies by using 99mTc-HM-PAO. They have been compared with radionuclide angiography and conventional tumor imagings such as 67Ga citrate or 201TlCl scanning, and then their possible values have been evaluated for the investigation of tumor blood flow. Tumors were clearly visualized in 19 out of 32 sites, with 59% of positive rate. Good correlation was observed between the radioactivity in the tumor site on static image of 99mTc-HM-PAO and the radioactivity at arterial phase on radionuclide angiography, which represents tumor blood flow. The radioactivities in the marginal regions tended to be stronger than those in the center of large tumors. These results indicated that tumor imaging by 99mTc-HM-PAO mainly reflected tumor blood flow. On the other hand, 99MTc-HM-PAO imagings were not well correlated with 67Ga-studies, while they were coincided with all 201Tl scannings performed. It suggested that the affinity of 99mTc-HM-PAO to capillary wall also involved in its accumulation in the tumor. In conclusion, tumor imaging by 99MTc-HM-PAO was able to estimate tumor blood flow, and this examination would be helpful for the management of malignancies.

Adult↗