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N Tonami

Publications and source records attributed to N Tonami.

At least 91 records · Page 5Linked to original sources
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

Prediction of prognosis in peripheral facial nerve paralysis using submandibular gland scintigraphy.

UNLABELLED: In this study, we evaluated the ability of submandibular gland scintigraphy to predict the prognosis of peripheral facial nerve paralysis. METHODS: Submandibular gland scintigraphy was performed in 78 patients with acute peripheral facial nerve paralysis. After injection of 180-370 MBq [99mTc]pertechnetate, serial 1-min images were acquired for 25 min. At 15 min after injection of radionuclide, ascorbic acid was administered intraorally to stimulate salivary secretion. Regions of interest were set manually on both submandibular glands, and time-activity curves were generated. The ratios of peak count density (PCR) and washout (WR) of the affected side to the normal side were calculated. Parameters of > or = 0.8 suggested normal affected submandibular function and indicated a good prognosis. RESULTS: Complete recovery of facial nerve paralysis was observed in 52 of 78 patients. The sensitivity, specificity and accuracy of PCR for a good prognosis were 79%, 50% and 69%, and those of WR were 85%, 77% and 82%, respectively. Positive and negative predictive values for a good prognosis were 76% and 54% in PCR and 88% and 71% in WR, respectively. When WR obtained within 14 days of the onset was used, positive and negative predictive values for a good prognosis were 94% and 73%, respectively. None of the eight patients who had values of <0.8 for both parameters within 14 days of the onset recovered completely. CONCLUSION: Submandibular gland scintigraphy can serve as a reliable indicator to predict the prognosis of acute peripheral facial nerve paralysis in its early symptomatic period.

Acute Disease↗
PubMed1998

Assessment of P-glycoprotein in patients with malignant bone and soft-tissue tumors using technetium-99m-MIBI scintigraphy.

UNLABELLED: Overexpression of P-glycoprotein (Pgp) has been detected in many malignant tumors including bone and soft-tissue tumors. Technetium-99m-MIBI has proved to be a transport substrate for Pgp. The purpose of our study was to explore 99mTc-MIBI as a functional imaging agent reflecting Pgp expression in malignant bone and soft-tissue tumors. METHODS: Technetium-99m-MIBI scintigraphy was performed in 30 patients with malignant bone and soft-tissue tumors. Radionuclide angiography with 99mTc-MIBI was done and, at 15 min and 3 hr postinjection of the radiopharmaceutical, imaging was performed. The 99mTc-MIBI uptake ratio was calculated by dividing the lesion count by the background count. The washout rate (WR) for 99mTc-MIBI was calculated by the following formula: WR = 100 x [(Te-Be)-(Td-Bd)]/(Te-Be) (%), where Te and Td = decay-corrected count density of the tumor in the 15-min and 3-hr images, respectively. Be and Bd = decay-corrected count density of the background in the 15-min and 3-hr images, respectively. The lesions were resected by open biopsy to obtain a histopathological diagnosis, and immunohistochemical staining was performed to detect Pgp. RESULTS: Twenty-four of 30 patients showed significant uptake at the 15-min image. In these 24 patients, the lesions with a high Pgp expression showed a similar 99mTc-MIBI perfusion index (3.00 +/- 1.04) and uptake ratio (2.05 +/- 0.58) at the 15-min image to those of lesions without a high Pgp expression (2.65 +/- 0.85 and 2.28 +/- 0.64, respectively). On delayed images, the 99mTc-MIBI uptake ratio was lower in patients with a high Pgp expression than in patients without a high Pgp expression (1.37 +/- 0.41 versus 1.87 +/- 0.39, p < 0.01). The washout ratio of 99mTc-MIBI was higher in patients with a high Pgp expression than in patients without a high Pgp expression (66% +/- 25% versus 29% +/- 18%, p < 0.001). None of the 6 patients without 99mTc-MIBI uptake at the 15-min imaging showed 201TI uptake, and only 2 had a high Pgp expression. CONCLUSION: In malignant bone and soft-tissue tumors, perfusion and initial 99mTc-MIBI uptake were not related to the Pgp expression; however, washout of 99mTc-MIBI from the tumor was related to Pgp expression. Technetium-99m-MIBI scintigraphy with washout analysis may be a useful method for the evaluation of Pgp overexpression and its function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Estimation of cardiac output by first-pass data with technetium-99m-labeled myocardial perfusion imaging agent].

Technetium-99m-tetrofosmin, a myocardial perfusion imaging agent was used for estimation of cardiac output by means of first-pass radionuclide angiography performed in the anterior projection. Region of interests (ROIs) were assigned over right ventricle, left ventricle and whole chest, and time activity curves (TACs) were obtained. Cardiac output indices (COIs) were calculated by the following equation; COI = p3/2. Qc/[symbol: see text] A(s)ds, where p = number of pixels of the ventricular ROI, Qc = the peak count rate of the TAC obtained from the whole chest's ROI and [symbol: see text] A(s)ds = the area under ventricular TAC. The COI (y) determined by ROI over the left ventricle yield the best correlation with the cardiac output by conventional radionuclide method (x) (y = 0.0381x + 6.22, r = 0.828, n = 48, p < 0.001). In conclusion, cardiac output can be easily measured with first pass data using myocardial perfusion imaging agent.

Adult↗
PubMed1998

Midcourse thallium-201 scintigraphy to predict tumor response in bone and soft-tissue tumors.

UNLABELLED: The purpose of this study was to assess the predictive power of 201TI scintigraphy in the midcourse of chemotherapy for the final tumor response to chemotherapy in malignant bone and soft-tissue tumors. METHODS: The 21 patients studied with 201TI scintigraphy were 14 males and 7 females (average age 39.8+/-22.1 yr; age range 8-74 yr). Planar scintigraphy was performed 15 min after injection of 111 MBq 201TI before chemotherapy, after the third chemotherapy cycle (midcourse) in all 21 patients and after the final chemotherapy cycle but before surgery in 11 patients. The 201TI uptake ratio was calculated by dividing the count density of the lesion by that of the contralateral normal area. The percent reduction of the 201TI uptake ratio calculated by 100 x [(prechemotherapy ratio - postchemotherapy ratio)/prechemotherapy ratio] in the midcourse was compared with that after the final course of chemotherapy, and it also was compared with the histologic response. RESULTS: In patients with histologically complete response [(CR), n=6] and with partial response [(PR), n=5], the percent reduction in 201TI uptake ratio after three cycles of chemotherapy was 64.1%+/-14.4% and 50.9% +/-10.5%, respectively. In patients with histologically no change [(NC), n=10], the percent reduction was 0.40%+/-18.2% after the third cycle; -5.3%+/-20.9% in four patients with full courses of chemotherapy (p < 0.0001 and p < 0.005 compared with the CR and PR groups, respectively). After the final cycle of chemotherapy, the percent reduction in 201TI uptake ratio was 68.6%+/-14.7%, 56.2%+/-6.1% and -0.3%+/-17.2% in the CR, PR and NC groups, respectively (NC versus CR, p < 0.0005; NC versus PR, p < 0.005). CONCLUSION: Thallium-201 scintigraphy performed in the midcourse of chemotherapy is predictive of the final response to chemotherapy that can be demonstrated histologically. Serial 201TI scintigraphy in the midcourse of chemotherapy is useful in assessing final chemotherapeutic response in the early stage of chemotherapy, and it helps clinicians when choosing the most appropriate treatment strategies in patients with bone and soft-tissue tumors.

Adolescent↗
PubMed1998

Absent myocardial iodine-123-BMIPP uptake and platelet/monocyte CD36 deficiency.

UNLABELLED: Global absence of myocardial 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) uptake is occasionally noted, and it reflects myocardial long-chain fatty acid uptake abnormality. CD36, a membrane glycoprotein expressed on platelet, monocyte and endothelial cells, may contribute to myocardial fatty acid transport, and its deficiency has been reported in a small subset of the population. We hypothesized that CD36 deficiency may be related to absent myocardial BMIPP uptake. Thus, we investigated CD36 expression of platelet/monocyte in patients with absent myocardial BMIPP uptake. METHODS: Peripheral blood of 7 patients with global absence of myocardial BMIPP uptake (3 of 7 patients in one family) and 3 control subjects were examined in flow cytometric analysis. Platelet/monocyte surface CD36 was detected by using OKM5, an anti-CD36 mouse monoclonal antibody. RESULTS: There were no apparent relationships between specific clinical symptoms and absent myocardial BMIPP uptake. None of the blood samples of the 7 patients were stained with OKM5 on the platelet/monocyte cell surface, indicating that all of these patients were Type I CD36-deficient subjects. In contrast, all the control subjects showed normal staining. CONCLUSION: The fact that rare Type I CD36 deficiency was observed in all patients with absent myocardial BMIPP uptake suggests that CD36 plays a role in the myocardial long-chain fatty acid uptake process in humans.

Adult↗
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↗
PubMed1998

[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↗
PubMed1998

[Evaluation of the safety and clinical feasibility of exercise 99mTc-MIBI SPECT using one day protocol--multicenter phase III clinical trial report].

We evaluated the safety and clinical usefulness of the same day protocol of exercise 99mTc-MIBI SPECT in 107 patients with heart diseases. No adverse event was observed except for one case of transient hypotension caused by the exercise. More than 95% of stress images and all of the rest images were judged as "Excellent" or "Good" in image quality. Overall sensitivity was 84.3% in detecting coronary artery disease, and no statistical difference was observed between the results obtained with Re-Ex and Ex-Re protocols. The examination was "Quite Effective" or "Effective" in diagnostic efficacy in 96.2% of the cases. We concluded that the same day protocol is a safe and useful method for diagnosing myocardial ischemia, which provides high image quality and valuable information.

Adult↗
PubMed1997

Discrepancy between blood flow and muscarinic receptor distribution in rat brain after middle cerebral artery occlusion.

To clarify whether muscarinic acetylcholine receptor (mAChR) binding can be a viable muscarinic neuronal marker which provides therapeutic information different from perfusional information in global brain, we evaluated the discrepancy between the distribution of cerebral blood flow (CBF), mAChR and its five subtypes of messenger ribonucleic acid (mRNA) in the acute (n=9) and chronic (n=8) phases of a middle cerebral artery (MCA) occlusion model and in sham-operated controls (n=6). In the acute phase, regional CBF was markedly reduced in the MCA territory, whereas mAChR was not reduced and the mRNA was reduced only slightly. In the chronic phase, mAChR was reduced markedly in the infarcted lesion and the mRNA was also reduced. The mAChR was slightly reduced in the ipsilateral substantia nigra and pontine nucleus because of remote effects; however, regional CBF in the substantia nigra was slightly increased and did not change in the pontine nucleus. The discrepancy between CBF and mAChR was clarified, and the tendency toward a reduction in mRNA in the acute ischaemic region without a reduction in mAChR suggested the presence of cholinergic neurons which were viable but hypometabolic. It is concluded that mAChR imaging may be of value for the assessment of the viable cholinergic neuron density in vivo.

Animals↗
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

Functional imaging of gated Tc-99m tetrofosmin study as a simple method to quantify ventricular wall motion.

Myocardial perfusion scintigraphy with wall motion analysis is known to enhance accuracy in diagnosing ischemic heart disease. The purpose of this study is to determine the best method to evaluate regional wall motion in a gated planar perfusion study. Planar gated 99mTc tetrofosmin (GTF) study in two projections was performed after rest-exercise sequence SPECT studies (n = 29). To evaluate wall motion, cine-mode display, wall thickening, and inverted tetrofosmin studies including ventricular inner border tracing, segmental wall shortening and functional images were used. The results were compared with gated blood-pool (GBP) study in the same projections. In the GTF study, functional image identified asynergy significantly better than cinematic display. The best correlation between GTF and GBP studies was observed with functional images of phase and amplitude, with complete visual agreement seen in 145 of 168 (86%) segments. With quantitative analysis by means of regions of interest (n = 280), a good correlation was observed between GTF and GBP regarding regional amplitude (r = 0.78), regional phase (r = 0.84), average left ventricular phase (r = 0.91) and standard deviation of phase values (r = 0.90). The value for the count-based "ejection fraction" derived from inverted GTF showed insufficient correlation to that of the GBP study (r = 0.69). Functional imaging with myocardial perfusion imaging is a simple and effective means to evaluate ventricular asynergy. Similar diagnostic criteria to gated blood-pool imaging and comparable diagnostic accuracy are advantages of this approach.

Aged↗
PubMed1997

Comparison of flow capacities of arterial and venous grafts for coronary artery bypass grafting: evaluation with exercise thallium-201 single-photon emission tomography.

Stress thallium-201 tomography was performed to compare the flow capacities of arterial and saphenous vein grafts in patients with coronary artery bypass grafting (CABG). One hundred and seven consecutive patients (95 male and 12 female; mean age 58+/-9.1 years) underwent exercise-redistribution 201Tl myocardial single-photon emission tomography 4-5 weeks after CABG. When a reversible perfusion defect was present in the area covered by a patent bypass graft, the flow capacity of the graft was defined as insufficient. Of all 285 grafts, 211 were considered as complete bypass. Reversible perfusion defects were present in 29 (27%) of 108 myocardial areas supplied by patent arterial grafts but in only 5 (5%) of 103 myocardial areas supplied by patent saphenous vein grafts (P<0.0001). In the LAD area reversible defects were observed in 22 of 82 areas covered by arterial grafts, in contrast to only 1 of 29 areas covered by venous grafts (P<0.01); in the RCA area reversible defects were observed in 7 of 17 and 4 of 41 areas respectively (P<0.01). There was no difference between the native coronary artery stenosis bypassed by patent arterial and venous grafts (88%+/-12% vs 86%+/-14% respectively, P=0.27). In conclusion, flow capacities during peak myocardial demand were more frequently insufficient in arterial bypass grafts than in saphenous vein grafts.

Coronary Artery Bypass↗
PubMed1997

Quantitative rest technetium-99m tetrofosmin imaging in predicting functional recovery after revascularization: comparison with rest-redistribution thallium-201.

OBJECTIVES: This study was undertaken to 1) compare the regional myocardial tracer distributions between rest technetium (Tc)-99m tetrofosmin and rest-redistribution thallium (Tl)-201 images in patients with coronary artery disease and left ventricular dysfunction; and 2) assess the comparative values of these agents for predicting functional recovery after revascularization. BACKGROUND: Tc-99m tetrofosmin is a new myocardial perfusion imaging agent, but its role for detecting viable myocardium is still unclear. METHODS: Thirty-six patients with coronary artery disease and left ventricular dysfunction underwent rest Tc-99m tetrofosmin, rest-redistribution Tl-201 and gated blood pool scintigraphy. In 21 patients with successful revascularization confirmed by follow-up angiography, gated blood pool scintigraphy was repeated after revascularization. Optimal threshold cutoffs to separate reversible from irreversible dysfunction were determined by receive operating characteristic analysis. RESULTS: Regional Tc-99m tetrofosimin activity highly correlated with redistribution Tl-201 activity (r = 0.93). The diagnostic performance for predicting functional recovery, as measured by the area under the receiver operating characteristic curves, measured 0.66 +/- 0.07 (mean +/- SD) for Tc-99m tetrofosmin and 0.67 +/- 0.07 for Tl-201 (p = 0.60, 96.7% power to detect difference in area of 0.10). The optimal threshold cutoffs for viability were considered to be 50% of peak activity for Tc-99m tetrofosmin and 55% of peak activity for Tl-201. The positive and negative predictive values for reversible dysfunction were, respectively, 69% and 82% for Tc-99m tetrofosmin and 69% (p = 0.99 vs. Tc-99m tetrofosmin) and 71% (p = 0.66 vs. Tc-99m tetrofosmin) by Tl-201. CONCLUSIONS: The diagnostic performance of quantitative rest Tc-99m tetrofosmin imaging in predicting functional recovery after revascularization is comparable to that of rest-redistribution Tl-201.

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↗