Biomedical subjects

Noriyuki Shuke

Publications and source records attributed to Noriyuki Shuke.

27 records · Page 2Linked to original sources

PubMed2003

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by 123I-BMIPP SPECT and 99mTc-tetrofosmin electrocardiographically gated SPECT.

OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p > 0.05) but had a significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p < 0.005) and perfusion (p < 0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.

Adolescent↗

PubMed2003

Improved accuracy in estimation of left ventricular function parameters from QGS software with Tc-99m tetrofosmin gated-SPECT: a multivariate analysis.

UNLABELLED: The purpose of this study was to verify whether the accuracy of left ventricular parameters related to left ventricular function from gated-SPECT improved or not, using multivariate analysis. METHODS: Ninety-six patients with cardiovascular diseases were studied. Gated-SPECT with the QGS software and left ventriculography (LVG) were performed to obtain left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV). Then, multivariate analyses were performed to determine empirical formulas for predicting these parameters. The calculated values of left ventricular parameters were compared with those obtained directly from the QGS software and LVG. RESULTS: Multivariate analyses were able to improve accuracy in estimation of LVEF, EDV and ESV. Statistically significant improvement was seen in LVEF (from r = 0.6965 to r = 0.8093, p < 0.05). Although not statistically significant, improvements in correlation coefficients were seen in EDV (from r = 0.7199 to r = 0.7595, p = 0.2750) and ESV (from r = 0.5694 to r = 0.5871, p = 0.4281). CONCLUSION: The empirical equations with multivariate analysis improved the accuracy in estimating LVEF from gated-SPECT with the QGS software.

Adolescent↗

PubMed2003

Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy.

Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radioimmunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I-A7 and i.p. administered irrelevant 131I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n = 11), mice undergoing i.p. RIT with 131I-A7 (n = 11), mice undergoing i.v. RIT with 131I-A7 (n = 11) and mice undergoing non-specific i.p. RIT with 131I-HPMS-1 (n = 5). Intraperitoneal injection of 131I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2 +/- 16.5% of the injected dose per g (% ID/g) and 11.1 +/- 3.6% ID/g at 2 h, respectively (P < 0.0001). Consequently, cumulative radioactivity in tumors was 1.73-fold higher with i.p. injection. 131I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131I-HPMS-1 (mean survival, 26.0 +/- 2.5 days) did not affect the survival as compared to no treatment (26.7 +/- 1.9 days). Intravenous RIT with 131I-A7 prolonged the survival of mice to 32.8 +/- 1.8 days (P < 0.01). Intraperitoneal RIT with 131I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P < 0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.

Animals↗

PubMed2003

Functional mapping of regional liver asialoglycoprotein receptor amount from single blood sample and SPECT.

UNLABELLED: The objective of this study was to validate a method for estimating regional liver asialoglycoprotein (ASGP) receptor amount from single blood samples using static SPECT with (99m)Tc-diethylenetriaminepentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA). METHODS: Based on a 2-compartment nonlinear model, regional ASGP receptor amount could be calculated from total liver ASGP receptor amount (Ro) and regional GSA uptake at a specific time. Because Ro could be estimated from single blood samples using an empiric formula, regional GSA uptake obtained as a SPECT voxel count could be converted to regional ASGP receptor amount by solving a nonlinear model equation. To validate this method, data from 62 patients with chronic liver disease underwent dynamic SPECT (30 rotations per 30 min) and simultaneous multiblood sampling and were analyzed by this method. Ro was calculated as the sum of voxel values of parametric receptor images generated from plasma concentration of GSA at 20 min and of static SPECT images generated by merging dynamic SPECT data (12-20 min). Ro was also estimated by fitting time-activity curves (4-30 min) of plasma and whole liver to the nonlinear model using the nonlinear regression method. Ro obtained from the receptor image was compared with that from curve fitting in relation to the results of hepatic function tests (indocyanine green test, hepaplastin test, and branched-chain amino acids/tyrosine plasma concentration ratio) and Child's classification. RESULTS: Ros from the 2 methods showed a significant linear correlation (r(2) = 0.938; P < 0.0001; slope = 0.90; y-intercept = 1.5). Both Ros had significant correlations with the results of hepatic function tests (P < 0.001) and differed significantly among the 3 groups of Child's classification (P < 0.0001). CONCLUSION: The present method could provide a quantitative ASGP receptor image without dynamic data acquisition. This approach could be useful for quantitative evaluation of regional liver function and estimation of residual liver function in hepatectomy.

Adolescent↗

PubMed2002

Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells.

The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tumour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current investigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metastases were established in nude mice by intrasplenic inoculation of LS180 colon cancer cells; following such inoculation, metastases of <1 mm in diameter can be observed at 1 week and these lesions can attain a size of several millimetres at 2 weeks. Daily AT with 2-methoxyoestradiol (2-ME), 75 mg/kg, was initiated at 1 week. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, (131)I-HPMS-1, was implemented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on (131)I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or (131)I-A7 RIT significantly suppressed metastasis growth ( P<0.0001): metastasis weight was 5.96+/-0.87 g in non-treated controls, 2.67+/-1.89 g in cases receiving AT and 0.85+/-0.68 g in those receiving (131)I-A7 RIT. Combination of AT and (131)I-A7 RIT more effectively suppressed the growth to 0.28+/-0.32 g ( P<0.05 vs RIT alone). The effect of (131)I-HPMS-1 RIT, which suppressed metastasis growth to 2.25+/-0.88 g, was significant in comparison with the control ( P<0.0001); however, the combination of AT and (131)I-HPMS-1 RIT (which suppressed growth to 1.41+/-0.68 g) was far less effective than the combination of AT and (131)I-A7 RIT. AT did not decrease (131)I-A7 accumulation in metastases. AT did not affect RIT myelotoxicity. The results of this study demonstrating the combined effects of AT and (131)I-A7 RIT in a small metastasis model indicate that such combination therapy may be suitable for the treatment of minimal disease.

Angiogenesis Inhibitors↗

PubMed2002

Hypoxia-induced alteration of tracer accumulation in cultured cancer cells and xenografts in mice: implications for pre-therapeutic prediction of treatment outcomes with (99m)Tc-sestamibi, (201)Tl chloride and (99m)Tc-HL91.

Weak visualization of tumours in pre-therapeutic scintigrams with technetium-99m sestamibi (MIBI) is likely a predictive sign of unfavourable tumour response to radiotherapy and chemotherapy. However, factors relating to this scintigraphic finding are not well understood. The presence of hypoxic tumour cells is one of the major reasons for therapeutic failure; consequently, we attempted to determine whether oxygenation status affects (99m)Tc-MIBI accumulation in tumour cells. LS180 human colon cancer and T24 human bladder cancer cells were incubated in air or N(2) gas at 37 degrees C. Cellular uptake of (99m)Tc-MIBI was subsequently determined at 15, 60 and 120 min. Uptake of thallium-201 chloride was also assessed. Uptake of (99m)Tc-HL91 was assessed as a hypoxic marker. Accumulation of the tracers in LS180 xenografts was observed in mice treated with 5 mg/kg hydralazine and compared with that in untreated mice. pO(2) in the medium and tumours was measured with O(2) microelectrodes. N(2) gas flow gradually reduced pO(2) in the cell suspension to 1-2 mmHg in 60 min. Cellular uptake of (99m)Tc-MIBI in LS180 cells decreased by approximately 30% in N(2) gas in comparison to that in air throughout the study. Hypoxia had a more prominent influence on (201)Tl uptake, which displayed a reduction of approximately 60% in N(2) gas at 120 min, than on (99m)Tc-MIBI uptake. On the other hand, N(2) gas induced an increase of 170% in (99m)Tc-HL91 uptake at 120 min, indicating the hypoxic condition of cells. The results of in vitro assays employing the T24 cell line were similar to those obtained with the LS180 cell line. Hydralazine treatment markedly reduced (99m)Tc-MIBI and (201)Tl accumulation in LS180 xenografts; moreover, intratumoural pO(2) decreased from 14.5 +/- 6.6 mmHg to 7.6 +/- 6.2 mmHg. (99m)Tc-HL91 accumulation in xenografts was markedly increased by hydralazine. In conclusion, hypoxia reduced accumulation of (99m)Tc-MIBI and (201)Tl in tumour cells. Accordingly, hypoxia may be an important factor in terms of the interpretation of scintigraphic findings obtained with these tracers for pre-therapeutic prediction of tumour response to treatment. Furthermore, the enhanced (99m)Tc-HL91 accumulation in hypoxic tumour cells indicates the usefulness of this tracer in this regard.

Animals↗

PubMed2002

Radioimmunotherapy with 186Re-labeled monoclonal antibody to treat liver metastases of colon cancer cells in nude mice.

The efficacy of radioimmunotherapy (RIT) in the treatment of minimal disease has been previously shown, despite the limitation of beta-emitters suggested by a mathematical model. In the present study, the efficacy of RIT with an anti-colorectal cancer IgG1 A7 conjugated with 186Re was examined in a liver metastasis model established by intrasplenic inoculation of human colon cancer cells. In this model, small metastases of less than 1 mm in diameter can be observed 1 week after cell inoculation. Metastases attain a diameter of several millimeters at 2 weeks. 186Re-A7 accumulated exclusively in metastases, displaying a value of 24.1 +/- 8.7% ID/g 2 days after the injection. 186Re-A7 accumulation in liver metastases increased with decreasing size. RIT with 7 MBq 186Re-A7 at 2 weeks significantly suppressed the growth of metastases; weight of metastases 4 weeks after cell inoculation was 5.96 +/- 0.87 g in nontreated control mice and 1.25 +/- 0.75 g in mice receiving 186Re-A7 RIT (p < 0.0001). RIT at 1 week more effectively inhibited metastatic growth to 0.08 +/- 0.05 g (p < 0.002 vs. RIT at 2 weeks). RIT with a class-matched irrelevant MAb 186Re-HPMS-1 at 1 week after cell inoculation somewhat suppressed metastatic growth, 3.39 +/- 0.25 g at 4 weeks, as compared with the control; however, 186Re-HPMS-1 RIT was far less effective than 186Re-A7 RIT (p < 0.0001). These results support the use of RIT with 186Re-MAb in an adjuvant setting in cases involving minimal disease. Factors such as higher and homogeneous MAb accumulation in small nodules, better perfusion, and subsequent better oxygenation likely compensate for the loss of beta radiation outside small metastases.

Animals↗

PubMed2002

Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts.

UNLABELLED: Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth. METHODS: Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq (131)I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections. RESULTS: Antiangiogenic therapy and RIT with (131)I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using (131)I-HPMS-1 was far less effective than (131)I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy). CONCLUSION: The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.

Angiogenesis Inhibitors↗

PubMed2001

Relation between technetium 99m-methoxyisobutylisonitrile accumulation and multidrug resistance protein in the parathyroid glands.

Technetium 99m ((99m)Tc)-methoxyisobutylisonitrile (MIBI) scintigraphy has been reported to be a useful method for visualizing the parathyroid glands for the diagnosis of hyperparathyroidism. Some drug metabolism transporters, such as p-glycoprotein (P-GP) or multidrug resistance-associated protein (MRP), are believed to be involved with one mechanism of (99m)Tc-MIBI accumulation in the parathyroid glands. We analyzed the expression of P-GP and MRP in 40 parathyroid glands from eight patients with primary hyperparathyroidism and six patients with secondary hyperparathyroidism using an immunohistochemical procedure. These patients underwent (99m)Tc-MIBI scintigraphy and thallium 201 ((201)Tl)/(99m)Tc subtraction scintigraphy preoperatively. We investigated the relation between the scintigraphic images and the expression of P-GP and MRP. The positive findings of (99m)Tc-MIBI accumulation in the hyperfunctioning parathyroids were increased significantly. There was a significant difference between the expression of P-GP and the (99m)Tc-MIBI scintigraphy findings. High expression of P-GP in parathyroid cells resulted in the negative image of (99m)Tc-MIBI, and low or no expression of P-GP made the image positive. There was no significant difference between the expression of MRP and the (99m)Tc-MIBI scintigraphic imaging. The (99m)Tc-MIBI image was also related to the weight of the parathyroid glands but not to the type of the parathyroid cells. Based on these clinical findings, we can hypothesize that P-GP functions as a drug transporter not only for chemotherapeutic agents but also for (99m)Tc-MIBI.

ATP Binding Cassette Transporter, Subfamily B, Mem↗