Biomedical subjects

S Kinuya

Publications and source records attributed to S Kinuya.

At least 91 records · Page 5Linked to original sources

PubMed1994

Effect of metabolism on retention of indium-111-labeled monoclonal antibody in liver and blood.

UNLABELLED: The effect of a chelator structure on the metabolic fate of the 111In-labeled monoclonal antibody (Mab) T101 was investigated in normal Balb/c mice to assess the importance of this chemical parameter in the reduction of the background radioactivity in blood and liver. METHODS: Mab T101 was conjugated with either 2-(p-isothiocyanatobenzyl)-6-methyl-diethylaminetriaminepentaac etic acid (DTPA) (1B4M), 2-(p-isothiocyanatobenzyl) cyclohexyl-DTPA (CHX-B) or cyclic DTPA dianhydride (cDTPA) and then radiolabeled with 111In. Normal mice were injected intravenously with these 111In-labeled T101 conjugates and sacrificed in groups of five up to 5 days postinjection for comparative biodistribution studies and analyses of liver, blood and urine samples for radioindium products. RESULTS: The biodistribution of 111In-1B4M-T101 and 111In-CHX-B-T101 were similar to each other but significantly different from that of 111In-cDTPA-T101, particularly in the blood and liver. Size-exclusion high-performance liquid chromatography indicated that the concentration of the intact 111In-immunoglobulin (Ig)G in liver decreased with similar rates for the three conjugates. Meanwhile, the concentration of a small DTPA-like metabolite in liver increased to a different peak value (4.6% ID/g for the cDTPA conjugate and 1.6% ID/g for the 1B4M and CHX-B conjugates) approximately at 24 hr and maintained a steady-state concentration up to 5 days. CONCLUSION: The thiourea linkage between T101 and the 111In-labeled chelates and a higher complex stability and higher lipophilicity of 111In-1B4M and 111In-CHX-B appear to be responsible for lower liver and higher blood radioactivity for the 1B4M and CHX-B conjugates.

Animals↗

PubMed1994

[A simple method to obtain semi-quantitative index of brain perfusion using 99mTc-HMPAO].

We developed a new noninvasive index (brain uptake ratio, BUR) inferring brain perfusion using 99mTc-HMPAO scintigraphy, and compared with the index (brain perfusion index, BPI) reported by Matsuda, et al. BUR was obtained for 208 cerebral hemispheres from 104 cases as a ratio of radioactivity in a brain against that passing through an aortic arch. BUR correlated well with BPI (r= 0.965, p < 0.01). Information in deep or occipital regions was reflected well to BUR when data of SPECT images were used. BUR can be obtained even with a small field-of-view gamma camera. BUR is easily obtained and thought to be useful as a semi-quantitative index of brain perfusion.

Adult↗

PubMed1994

Evaluation of the serum stability and in vivo biodistribution of CHX-DTPA and other ligands for yttrium labeling of monoclonal antibodies.

UNLABELLED: Serum stability and in vivo biodistribution of both A and B isomers of the 2-(p-isothiocyanatobenzyl) (p-SCN-Bz)-cyclohexyldiethylenetriaminepentaacetic acid ligand (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA, were evaluated and compared to those of 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) and 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetra-acetic acid (2B-DOTA). METHODS: Stability of 88Y-labeled ligands (0.1 microM) was evaluated in serum for up to 17 days. For biodistribution, ligands were conjugated to monoclonal antibody (Mab) B3, a murine IgG1k, and labeled with 88Y at 0.1-0.3 mCi/mg. Nontumor-bearing nude mice were injected intravenously with 1-2 microCi/4-10 micrograms of 88Y-labeled B3-conjugates and killed at 6 hr and daily up to 168 hr postinjection. Indium-111-(1B4M)-B3 was co-injected in all mice as internal control. RESULTS: Serum stability of 88Y-DOTA failed to show any significant release of activity, whereas pseudo-first-order dissociation rate constants of 3.97 x 10(-3), 2.54 x 10(-3) and 1.46 x 10(-2) (day-1) were calculated for 88Y-1B4M, 88Y-CHX-A and 88Y-CHX-B, respectively. Accordingly, cortical bone uptake of 88Y was significantly higher for all DTPA-derivative chelates than for DOTA. CONCLUSIONS: While none of the DTPA-derivative chelates could challenge DOTA in its ability to hold the radioytrium, significant differences were observed in the kinetic inertness of the A and B isomers of CHX, indicating that the CHX-B ligand is not as suitable for 90Y-labeling of Mabs.

Animals↗

PubMed1993

Preclinical evaluation of 111In-labeled B3 monoclonal antibody: biodistribution and imaging studies in nude mice bearing human epidermoid carcinoma xenografts.

Biodistribution and imaging characteristics of monoclonal antibody B3 were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. B3 is a murine IgG1k, recently isolated, reacting with a carbohydrate epitope abundantly and uniformly expressed by most carcinomas. B3 was conjugated to a new backbone-substituted derivative of diethylenetriaminepentaacetic acid, 2-(p-isothiocyanato benzyl)-cyclohexyl-diethylenetriaminepentaacetic acid, and labeled with 111In. Tumor-bearing mice were given i.v. injections of approximately 5 microCi of either 111In-B3 or 111In-MOPC-21, an isotype-matched control, and sacrificed in groups of five at 6 h and daily up to 168 h. Imaging was performed at 24, 72, and 144 h. Significant differences were observed in tumor uptake at all time points with peak values at 48 h (25 +/- 5.2% versus 6.3 +/- 0.4% of the injected dose/g tissue) (mean +/- SD) for 111In-B3 and 111In-MOPC-21, respectively (P < 0.001). All tumor to organ ratios increased with time for 111In-B3. In particular, tumor:liver ratios rose from 3.2 +/- 0.6 at 24 h to 6.3 +/- 1.2 at 168 h. Imaging results showed selective and progressive accumulation of 111In-B3 at the tumor site, whereas 111In-MOPC-21 did not show specific localization. In summary, 111In-labeled B3 demonstrated good and specific tumor targeting, which warrants its future clinical evaluation.

Animals↗

PubMed1993

Evaluation of a new DTPA-derivative chelator: comparative biodistribution and imaging studies of 111In-labeled B3 monoclonal antibody in athymic mice bearing human epidermoid carcinoma xenografts.

Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with 111In, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for 111In-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low liver accumulation of both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for 111In-labeling of MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent.

Animals↗

PubMed1993

Synthesis and biological evaluation of gallium polyaminothiols (PAT).

Two polyaminothiol ligands, one hexadentate, N,N',N"-tris[2-methyl(2-propanethiol)]-1,4,7-triazacyclononane (TACN), and another potentially heptadentate, tris[2-methyl(2-propanethiol)]aminoethylamine (TMAE), were synthesized and characterized using spectroscopic and analytical methods. Both ligands were labeled with gallium-67 at pH 3.0-3.5 in high yields. The resulting gallium chelates were lipophilic. The biodistribution studies for both the chelates showed hepatic uptake and biliary clearance. The total % ID activity for [67Ga]TACN in liver and intestine at 5 min was 33.86 increasing gradually to 61.4% at 30 min. The chelates were in vivo stable to plasma-transferrin transchelation as confirmed by scintigraphic images obtained by [67Ga]TACN in rats and by plasma incubation of the chelates. These results indicate that Ga-TACN is a potentially useful tracer for hepatobiliary imaging using PET. No brain uptake was found.

Animals↗

PubMed1993

An improved synthesis of [125I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma.

To improve the radiolabeling yield and the specific activity of [125I]N-(2-diethylaminoethyl)-4-iodobenzamide (DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [125I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [125I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung, was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma.

Animals↗

PubMed1993

Evaluation of suspected malignant pulmonary lesions with 201Tl single photon emission computed tomography.

201Tl single photon emission computed tomography (SPECT) was evaluated in 170 patients suspected of having a malignant pulmonary lesion greater than 20 mm in diameter on the surgical specimen. Delayed SPECT (at 3 h after injection) visualized all of the 147 malignant pulmonary lesions and 16 of the 23 (69.6%) benign pulmonary lesions, and generally exhibited the lesion more clearly than the early SPECT images (at 15 min after injection). There was no significant difference in delayed ratio (uptake ratio of the lesion to the normal lung on delayed scan) among the various histological groups except between the adenocarcinoma and large cell carcinoma groups (P < 0.05), and no difference was noted between the malignant and benign lesions. However, in retention index (degree of retention in the lesion) a significant difference was noted between the malignant and benign lesions (P < 0.01), although there was no significant difference in this index among malignant different histology groups. These results indicate that this method is useful for visualizing malignant pulmonary lesions greater than 20 mm in diameter to exclude the possibility of malignancy in the lesions when no abnormal 201Tl accumulation is observed. When the lesion shows abnormal 201Tl accumulation, the retention index seems to help differentiate malignant from benign lesions.

Adenocarcinoma↗

PubMed1993

A malignant melanoma imaging agent: synthesis, characterization, in vitro binding and biodistribution of iodine-125-(2-piperidinylaminoethyl)4-iodobenzamide.

In order to develop improved radiopharmaceuticals for imaging malignant melanoma, we have synthesized and characterized 125I-and 131I-labeled (2-piperidinylaminoethyl)4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl)4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-2 sites. In vitro homologous competition binding studies of [125I]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution studies in nude mice implanted with human malignant melanoma xenografts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24 hr) of [125I]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imaging with [131I]PAB in a nude mice model xenografted with human malignant melanoma at 24 hr clearly delineated the tumor with very little activity in any other organ. These results demonstrate that sigma-1 receptors could be used as external markers for malignant melanoma.

Animals↗

PubMed1992

Tc-99m HMPAO-labeled leukocytes for hematopoietic marrow imaging. Comparison with In-111 chloride.

The current study was initiated to define whether Tc-99m leukocyte imaging, compared to In-111 chloride imaging, could provide additional information on the hematopoietic activity of the bone marrow in diffuse hematologic disorders. A total of 11 patients with hematologic disorders were studied both with Tc-99m leukocytes and In-111 chloride. One patient with myelofibrosis showed disparate tracer distribution in the bone marrow between the two; Tc-99m leukocyte uptake in the central marrow was highly decreased, whereas In-111 chloride showed expanded marrow. The disparate results of granuloid hypoplasia and erythroid hyperplasia obtained by bone marrow biopsy and aspiration in this patient were thought to give an explanation for the radionuclide findings. The remaining 10 patients showed similar tracer distribution in the marrow, and the observation of hematopoietic cellularity confirmed by bone marrow biopsy and aspiration correlated well with the radionuclide findings. These results demonstrate that Tc-99m leukocytes may be a potential imaging agent for evaluating hematopoietic activity in the bone marrow, in particular granulopoietic activity.

Adult↗

PubMed1991

The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in primary biliary cirrhosis.

To assess the presence of primary biliary cirrhosis, 15 patients at various histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m colloid hepatic imaging. In the earlier stages (I and II), seven of eight patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod imaging. In three of these four negative patients (75%), uniform hepatic retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven patients showed decreased clearance with or without delayed tracer appearance in the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m colloid imaging there was enlargement of the spleen and increased activity in the spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful in revealing this functional disorder at the earlier stage of primary biliary cirrhosis and in evaluating progression from an earlier to a later stage of disease. Tc-99m colloid imaging also effectively evaluated progression.

Bone Marrow↗

PubMed1991

Tc-99m HMPAO SPECT analysis of neuroleptic effects on regional brain function.

This report describes a new approach to the evaluation of neuroleptic effects on regional brain function. Using Tc-99m HMPAO SPECT imaging, consecutive brain perfusion studies before and after acute haloperidol administration were performed on three schizophrenic patients and two normal volunteers. The antipsychotic drug ameliorated the hypoactivity in the frontal lobe and suppressed the hyperactivity in the temporo-occipito-parietal lobe selectively in the dominant hemisphere in the schizophrenic patients. It did not exert a significant influence on the brain perfusion pattern in normal volunteers. This nuclear medicine technique seems to be useful for the evaluation of drug effects in psychiatric diseases.

Adult↗

PubMed1991

201Tl SPECT in the detection of mediastinal lymph node metastases from lung cancer.

201Tl SPECT was performed to detect mediastinal involvement in 80 patients with lung cancer who underwent surgery within a week after the SPECT study. Out of 29 patients with mediastinal involvement 16 (55%) were positive on the 201Tl early scan at 15 min postinjection and 22 (76%) were positive on the delayed scan at 3 h. These metastatic lymph nodes tended to be visualized much better on the delayed scan. In all patients with true positive results on the delayed scan, the mediastinal lymph nodes were plural, with a lesion of more than 14 mm in size. Seven false negative cases were found to have metastatic lesions less than 12 mm in size. Both the early and delayed scans showed false positive accumulation in six of 51 patients without mediastinal involvement (specificity 88%). Thus the overall accuracy for the delayed scan was 84%. The 201Tl delayed SPECT is thought to be a good noninvasive method for assessing mediastinal lymph node metastases from lung cancer.

Aged↗

PubMed1991

[Clinical application of Tc-99m HMPAO labeled leukocyte imaging in inflammatory disease].

A radionuclide imaging with Tc-99m HMPAO labeled leukocyte was performed in order to determine its clinical usefulness in inflammatory disease. The mixed leukocyte isolated from 40 ml of whole blood containing 5 ml of acid citrate dextrose A and 7 ml of 6% hydroxyethyl starch was incubated with 370 MBq (10 mCi) of Tc-99m HMPAO at 37 degrees C for 30 minutes. Because the labeling efficiency of Tc-99m HMPAO labeled leukocyte was 60.2 +/- 6.3%, the procedure of washing Tc-99m, leukocyte with 5 ml of physiological saline was necessary before intravenous injection, in order to remove the unlabeled Tc-99m HMPAO. The recoveries of Tc-99m leukocyte in the blood after intravenous injection were 41.1 +/- 6.7% at 5 minutes, 33.4 +/- 2.1% at 30 minutes, and 27.2 +/- 3.4% at 2 hours after injection. Moreover, the labeled leukocyte was not stained with trypan blue. Therefore, the biological activity of the Tc-99m leukocyte was maintained as that of In-111 oxine labeled leukocyte. In the 39 patients with clinical suspicion of inflammatory disease including 15 patients with acute and chronic infectious disease where both Tc-99m leukocyte and Ga-67 citrate imagings were performed, the sensitivity, specificity and accuracy for infectious disease were 47%, 100% and 79% with Tc-99m leukocyte, and 67%, 79% and 74% with Ga-67 citrate. These results suggest that Tc-99m HMPAO labeled leukocyte imaging is promising for evaluating inflammatory disease because of the much higher specificity, the ready availability of Tc-99m HMPAO, the good image quality, and the lower radiation dose to the patient.

Gallium Radioisotopes↗

PubMed1991

[The diagnostic value of In-111 transferrin imaging in protein-losing gastroenteropathy].

The diagnostic value of In-111 transferrin abdominal imaging was studied in 17 patients with clinical suspicion of protein-losing gastroenteropathy, compared to that of alpha-1-antitrypsin fecal clearance test. The presence or absence of gastrointestinal protein-loss was finally decided based on the result of alpha-1-antitrypsin fecal clearance test (normal range, less than 13 ml/day) or of protein content measurement on the gastric juice (normal range, less than 71 mg/dl). In-111 transferrin was labeled in vitro. After intravenous administration, serial anterior abdominal images were obtained. All seven patients with a value equal to or more than 20 ml/day on the alpha-1-antitrypsin clearance test and two out of ten patients with a value less than 20 ml/day showed definite intestinal activity demonstrating protein-loss, and the loss-site was estimated by observing the movement of radiotracer within the bowel lumen. The patients with severe protein-loss showed the intestinal activity on the early image. In the patients with milder protein-loss, on the other hand, the activity was noted on the later image. All two patients with positive In-111 transferrin imaging and negative alpha-1-antitrypsin test were associated with protein-losing gastropathy, where a value of alpha-1-antitrypsin clearance was not increased because of denatured alpha-1-antitrypsin by acidic gastric juice and pepsin. These results suggest that In-111 transferrin abdominal imaging can be more useful for the diagnosis of protein-losing gastroenteropathy, because of its capabilities to evaluate the patients with gastropathy as well as to estimate the loss-site.

Adult↗

PubMed1990

Evaluation of inferior mesenteric vein blood flow circulation with per-rectal administration of thallium-201 and technetium-99m pertechnetate.

We administered both per-rectal thallium-201 (201Tl) and technetium-99m pertechnetate (99mTc) to patients with liver diseases in order to understand the abnormalities of inferior mesenteric vein (IMV) blood flow circulation. As 201Tl heart-to-liver uptake ratio (H:L), reflecting the degree of portal-systemic shuntings (PSS), increased, the visualization of IMV in general became poor on 99mTc scintigrams. 201Tl H:L in the group with no visualization of IMV on 99mTc scintigrams was significantly higher than in the group with clear visualization of IMV (p less than 0.001). However, there were patients who showed IMV visualization among those with high 201Tl H:L. In these patients, it was considered that IMV blood flowed in the normograde direction, escaping mainly through PSS at the upper part of the portal system, and resulting in elevated H:L. In the patients without IMV visualization, IMV blood flowed in the retrograde direction, escaping mainly through collaterals at the lower part of IMV. Inferior vena cava (IVC) was visualized on 99mTc scintigrams in some patients without IMV visualization, indicating the presence of collaterals from the distal part of IMV to IVC. Per-rectal studies using these two radiotracers can afford us useful informations on the abnormalities of IMV blood flow hemodynamics in patients with liver diseases.

Adult↗

PubMed1989

Indium-111 transferrin imaging for the diagnosis of protein-losing enteropathy.

For assessment of gastrointestinal protein loss, seven patients suspected of having protein-losing enteropathy were studied by gamma camera imaging using in-111 transferrin. Four patients with a value equal to or more than 20 ml/day on the alpha-antitrypsin clearance test or a high protein content on the gastric juice showed definite intestinal activity on an early image, demonstrating protein loss. The loss site could be determined by observing the movement of radiotracer within the bowel lumen on the subsequent images. The three patients with a value of less than 20 ml/day in the test showed no obvious intestinal activity throughout the study. Therefore, in-111 transferrin abdominal imaging appears to be useful for determining the loss site as well as for establishing the rapid diagnosis of protein-losing enteropathy.

Adult↗

PubMed1989

Thallium-201 single photon emission computed tomography in the evaluation of suspected lung cancer.

Thallium-201 SPECT was performed in 30 patients with suspected lung cancer. Both early and delayed scans demonstrated abnormal accumulation in all of 23 malignant pulmonary lesions including 21 lung cancer and in two of seven benign conditions. There were significant differences in delayed ratio (uptake ratio of the lesion to the normal lung on delayed scan) and retention index (degree of retention in the lesion) between lung cancer and benign conditions, respectively (p less than 0.01, p less than 0.05). The delayed ratio and retention index revealed that adenocarcinoma showed higher 201Tl accumulation than squamous cell carcinoma and small cell carcinoma (p less than 0.05) and 201Tl clearance in squamous cell carcinoma was faster than in the other two (p less than 0.05). Mediastinal involvement was detected in five of seven patients on delayed scans. The smallest lesion depicted was 1.5 cm in diameter. Two false negatives had small metastases less than 1.0 cm in diameter. This method seems to be useful to detect lung cancer, to differentiate malignant from benign lesions, and to evaluate mediastinal involvement from lung cancer.

Adenocarcinoma↗