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Noriyuki Shuke

Publications and source records attributed to Noriyuki Shuke.

At least 19 recordsLinked to original sources

Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal dissemination of human colon cancer cells in a murine model.

BACKGROUND AND AIM: In patients with a high risk of peritoneal dissemination of colon cancer, a treatment adjuvant to surgical resection would improve their prognosis. We aimed to determine whether radioimmunotherapy employing radiolabelled monoclonal antibody would work in this situation. METHODS: A murine model of peritoneal dissemination was established in female Balb/c nu/nu mice by intraperitoneal injection of LS180 human colon cancer cells. Radioimmunotherapy with 7.4 MBq of a murine IgG1, anti-colorectal A7 monoclonal antibody, radiolabelled with (131)I by the chloramine-T method was conducted intraperitoneally on days 0, 3, 7 and 14 after cell inoculation, respectively. RESULTS: Radioimmunotherapy at any timing improved survival of mice as compared with those of non-treated mice and mice treated with a daily dose of 30 mg x kg(-1) of 5-fluorouracil for 4 consecutive days. The best improvement was obtained when radioimmunotherapy was conducted on day 0. CONCLUSION: These results indicate that intraperitoneal radioimmunotherapy may effectively kill colon cancer cells disseminated in the peritoneal cavity before formation of tumours and, therefore, may work as an adjuvant treatment to prevent peritoneal metastasis of colon cancer.

Animals↗

99mTc-sestamibi to monitor treatment with antisense oligodeoxynucleotide complementary to MRP mRNA in human breast cancer cells.

OBJECTIVE: Technetium-99m sestamibi (MIBI) has been utilized to evaluate multi-drug resistance (MDR) phenomenon of malignant tumors and to predict chemotherapeutic effects on them. The current investigation examined the possibility of monitoring changes with respect to mRNA expression of multi-drug resistance associated protein (MRP) following antisense oligodeoxynucleotide (AS-ODN) treatment involving 99mTc-MIBI. METHODS: The human breast cancer MCF-7 cell line and its MDR-induced MCF-7/VP cell line were employed. Cell suspensions of the two cell lines at 1 x 10(4) cells/ml were inoculated in 24-well plates (0.2 ml/well) and incubated for one day. Antisense (AS) 20-mer phosphorothioate ODN complementary to the coding region of MRP mRNA and its sense (S) ODN were administered at final concentrations up to 25 microM, followed by a 5-day incubation. 99mTc-MIBI solution was added to each well and incubated for 30 min. Cellular 99mTc-MIBI uptake was corrected for protein concentration. MRP mRNA expression levels were analyzed via the reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Cellular uptake of 99mTc-MIBI in MCF-7/VP cells was only 15% of that of MCF-7 cells. Following AS-ODN treatment at 25 microM for five days, 99mTc-MIBI uptake in MCF-7/VP cells increased 2.4-fold in comparison with non-treated control cells. 99mTc-MIBI uptake in MCF-7 cells was unaffected by AS-ODN administration. Sense ODN did not alter uptake in either cell line. RT-PCR confirmed reduction of MRP mRNA in MCF-7/VP cells following AS-ODN treatment. CONCLUSION: Effects of AS-ODN administration on MRP function can be monitored via assessment of cellular uptake of 99mTc-MIBI.

Breast Neoplasms↗

Cerebral activation during withholding urine with full bladder in healthy men using 99mTc-HMPAO SPECT.

UNLABELLED: The aim of this study was to identify the brain areas that control urinary continence in healthy men by 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT. METHODS: SPECT scans were performed on 15 right-handed healthy male volunteers, 24-45 y old. Each subject was scanned twice without movement in a supine position, and 444 and 555 MBq 99mTc-HMPAO were separately injected intravenously during the following 2 conditions: resting state with an empty bladder and urine-withholding state with a full bladder. The final image during urine withholding was obtained by subtracting the first scan data from the second scan data. The images were analyzed by statistical image analysis software and displayed on Z-score images at a significance threshold of P < 0.05 with correction for multiple comparisons. RESULTS: In the urine-withholding state, as compared with resting, there was a significant increase in tracer activity in the bilateral inferior frontal gyri and the right superior and the middle temporal gyri. Among the regions, the right inferior frontal gyrus was distinctly prominent. When the threshold value was decreased to P < 0.005 without correction, there was a vast network of cortical and subcortical regions involved during urine withholding. CONCLUSION: Our results suggest that the right inferior frontal gyrus plays an important role in brain control of urinary continence. This study also suggests that brain control of continence can be confirmed by statistical image analysis software using SPECT.

Adult↗

Locoreginal radioimmunotherapy with 186Re-labeled monoclonal antibody in treating small peritoneal carcinomatosis of colon cancer in mice in comparison with 131I-counterpart.

The efficacy of locoregional radioimmunotherapy (RIT) in treating peritoneal tumors of colon cancer of <2 mm in diameter was examined at maximum tolerated doses, focusing the comparison between 186Re and 131I labeled to an anti-colorectal cancer IgG1. Estimated radiation doses to tumors were considerably higher with 186Re-RIT than with 131I-RIT. The advantage of 186Re-RIT decreased with decreasing tumor size, but 186Re-RIT delivered 1.6-times higher radiation to tumors of 1 mm. Consequently, 186Re-RIT attained better survival of mice than 131I-RIT or chemotherapy with 5-fluorouracil did. Therefore, locoregional 186Re-RIT may be an option in an adjuvant setting of colon cancer with high risk of peritoneal dissemination.

Animals↗

Impaired cardiac sympathetic nerve function in patients with Kawasaki disease: comparison with myocardial perfusion.

Kawasaki disease (KD) is a leading cause of CAD in children. The impairment of cardiac sympathetic nerve function (CSNF) in the adult patients with coronary artery disease (CAD) could often be seen. However, little is known concerning the impairment of CSNF in KD patients. We investigated CSNF and its relationship with myocardial perfusion in KD patients. Eleven children with KD and 4 controls were studied with 123I-metaiodobenzylguanidine (MIBG) and stressed 201Tl single photon emission computed tomography. By the findings on coronary artery angiography (CAG), the patients were divided into 2 groups: A, without stenosis; B, with significant stenosis and/or old myocardial infarction. CSNF was evaluated from the uptake of 123I-MIBG. While myocardial perfusion was evaluated from 201Tl uptake. The numbers of patients in the groups A and B were 7 and 4. Perfusion defect was found in 0, and 2 patients in group A (0%), and B (50%). 123I-MIBG defects were found in 1 and 4 patients in the group A (14%) and B (100%). There were excellent concordances between the finding of 201Tl and 123I-MIBG in group A. While in group B, the coronary territories with 123I-MIBG defects were significantly more than those with perfusion defects (p < 0.05). In KD patients, the impairment of CSNF might be subsequent to coronary artery stenosis and was more severe than the injury of myocardial perfusion.

3-Iodobenzylguanidine↗

Evaluation of normal fatty replacement of the thymus with chemical-shift MR imaging for identification of the normal thymus.

PURPOSE: To clarify the influences of age and gender on normal fatty replacement of the thymus in childhood, adolescence, and early adulthood using chemical-shift MRI. MATERIALS AND METHODS: A total of 95 normal subjects (52 males and 43 females, mean age = 15.6 years, range = 7-25 years) who underwent chemical-shift MRI of the thymus were assessed prospectively. Signal intensity loss (SIL) of the thymus was determined by dividing the thymus/muscle ratio on the opposed-phase image by that on the in-phase image. We evaluated SIL for its correlation with age and gender, and assessed SIL of the thymus with uncommon morphological features. RESULTS: A significant correlation was found between SIL and age (r = 0.750, P < 0.001). There was no significant difference in SIL between the genders. No significant SIL was identified in any of the subjects aged 10 years or less. However, significant SIL was found in 70.8% of those aged 11-20 years, 100% of those aged 21 years or more, and 46.2% of subjects with uncommon morphological features of the thymus. CONCLUSION: Chemical-shift MRI can depict physiologic fatty infiltration within the normal thymus in subjects over 11 years of age. It is crucial to correlate these normal age-related findings with clinical cases in order to avoid misinterpretation.

Adolescent↗

Anti-angiogenic therapy and chemotherapy affect 99mTc sestamibi and 99mTc-HL91 accumulation differently in tumour xenografts.

BACKGROUND: Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumulation of radiotracers such as 99mTc sestamibi (MIBI). Anti-angiogenic therapy is primarily cytostatic; consequently, its influence on tracer accumulation may differ from that of cytotoxic treatments. METHODS: Anti-angiogenic therapy employing 2-methoxyestradiol was administered in mice bearing subcutaneous xenografts of LS180 colon cancer cells. The effects of chemotherapy with 5-fluorouracil were examined as a cytotoxic counterpart. Treatments were conducted for 4 days from day 8. Distribution of 99mTc-MIBI and Tc-HL91, a hypoxic marker, was observed on days 8 and 12. Oxygen tension (PO2) in tumours was measured by a microelectrode. Cellular uptake of tracers was examined in vitro in normoxic and hypoxic conditions. RESULTS: 99mTc-MIBI accumulation decreased with increasing tumour weight when no treatment was conducted. Tumour growth was suppressed by anti-angiogenic therapy and chemotherapy. 99mTc-MIBI accumulation in tumours decreased after chemotherapy as compared to pre-therapeutic values, whereas accumulation of 99mTc-HL91 increased. In contrast, accumulation of tracers did not significantly change after anti-angiogenic therapy as compared to that observed pre-therapeutically. Tumour PO2 decreased with increasing tumour volume when no treatment was conducted. Chemotherapy reduced PO2 in tumours. PO2 in tumours treated with anti-angiogenic therapy was as high as that observed before treatment. 2-Methoxyestradiol or 5-fluorouracil did not significantly affect tracer accumulation in cells under both normoxic and hypoxic conditions in vitro. CONCLUSION: These findings indicate that scintigraphic assessment of therapeutic efficacy of anti-angiogenic therapy should be performed from a perspective distinct from that of cytotoxic treatment.

2-Methoxyestradiol↗

Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy.

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, or (131)I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation ( n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice ( n=8) ( P<0.05). (131)I-A7 RIT displayed a marked therapeutic effect ( n=8) ( P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of (131)I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy ( n=10) ( P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and (131)I-HPMS-1 RIT failed to provide an appreciable benefit ( n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.

Angiogenesis Inhibitors↗

Correct localization of epileptogenic focus with I-123 iomazenil cerebral benzodiazepine receptor imaging: a case report of temporal lobe epilepsy with discordant ictal cerebral blood flow SPECT.

A 26-year-old female with intractable epileptic seizures was studied with I-123 iomazenil cerebral benzodiazepine receptor, I-123 IMP inter-ictal and Tc-99m ECD ictal cerebral blood flow SPECT. The ictal cerebral blood flow SPECT indicated the location of the seizures to be in the left temporal lobe, where increased regional cerebral blood flow was noted in marked contrast to the inter-ictal SPECT. Ictal electroencephalograms (EEGs) recorded with scalp and sphenoidal electrodes also suggested the left temporal lobe as the location of the seizures. On I-123 iomazenil SPECT, however, decreased benzodiazepine receptor density was demonstrated in the right temporal lobe. MRI showed mild atrophy and abnormal signal intensity in the right temporal lobe. Ictal EEGs recorded with intracranial electrodes revealed that abnormal electrical activity of the brain always emerged from the right temporal lobe and then propagated to the contralateral side. Based on the findings of intracranial EEGs, partial resection of the right anterior temporal lobe including hippocampus was performed. After the surgery, no seizure occurred. Pathological examination of the surgical specimens revealed hippocampal sclerosis. This case suggested that cerebral benzodiazepine receptor imaging with I-123 iomazenil can be helpful for correct localization of epileptogenic foci.

Adult↗

Optimization of the uptake method for estimating renal clearance of 99mTc mercaptoacetyltriglycine.

OBJECTIVE: To improve the estimation of 99mTc mercaptoacetyltriglycine clearance in the renal uptake method by optimizing the conditions of renal depth, background, threshold for renal boundary determination, and time interval for integrating renal counts. METHODS: Dynamic renal imaging was performed in 232 patients with dual energy window acquisition (main, 140 +/- 14keV; sub, 122.5 3.5keV). For drawing renal regions of interest (ROIs), cut-off methods with 50% and 70% of the highest renal pixel counts were used. For drawing the backgrounds, circumferential and lateral-inferior quadrant peri-renal ROIs were used. For setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post-injection were used. For determining renal depth, three methods of a theoretical exponential function using scatter fraction, Tønnesen's formula, and linear combination of scatter fraction and Tønnesen's formula were used. The scatter fraction was calculated using the counts in renal ROIs in the two energy windows. Using every combination of these conditions, renal uptake was calculated. As a reference, one-sample clearance was calculated from a blood sample taken at 30 min post-injection following Bubeck's formula. According to the methods for estimating renal depth, three non-linear regression models were derived to convert renal uptake to clearance. Using one-sample clearance and integrated renal counts as dependent and independent variables, data were fitted to the models to determine the necessary constants. The correlations between the model estimated clearances and one-sample clearance were investigated. RESULTS: One-sample clearance ranged from 11 to 404 ml x min(-1) per 1.73 m2. More than half of the regression using renal depth determined by the scatter fraction alone failed to converge. Among the successfully converged regressions, all model estimated clearances showed significant correlations (P<0.01) with one-sample clearance. The best correlation was observed in the model using renal depth determined by the combination of scatter fraction and Tønnesen's formulas, renal ROIs by 50% cut-off, lateral-inferior background and time interval of 2-3 min (r=0.898, P<0.001). CONCLUSION: The renal uptake method for estimating the clearance of mercaptoacetyltriglycine can be improved by the processing conditions proposed here.

Adolescent↗

Limitations of (99m)Tc tetrofosmin in assessing reversal effects of verapamil on the function of multi-drug resistance associated protein 1.

BACKGROUND: Previous reports have demonstrated the feasibility of scintigraphic assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding cassette (ABC) transporters by using Tc cationic tracers such as Tc tetrofosmin (TF). Furthermore, the potential of these tracers for evaluating the effects of reversal agents for MDR has been documented. However, most reversal agents simultaneously affect cationic ion transporters related to tracer accumulation in tumours. METHODS: The uptake of Tc-TF was examined in the MCF7/WT cell line, a wild-type breast cancer cell line that does not exhibit MDR, and its subclonal etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one of the multi-drug resistance associated proteins (MRPs), in the presence of increasing concentrations of verapamil, a classical MDR modulator. In the absence of verapamil, MCF7/VP cells showed significantly lower Tc-TF uptake than did MCF7/WT cells, indicating that Tc-TF is a substrate for MRP1. The presence of verapamil enhanced the uptake of Tc-TF in MCF7/VP cells. On the other hand, verapamil also increased tracer uptake in MCF7/WT cells, which was readily appreciated when the uptake values were corrected by viable cell numbers: an approximately 100% increase of Tc-TF uptake was observed in comparison with that in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention of radioactivity in both MCF7/WT cells and MCF7/VP cells. CONCLUSION: These results suggest that cellular functions other than MRP1 function, probably cationic ion transporters, are simultaneously and significantly involved in the verapamil induced changes of cellular uptake of Tc-TF. Tc-TF scintigraphy may overestimate the reversal effects of modulators on chemoresistance caused by MRP1 when the modulators simultaneously affect ion transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The radiotoxicity of 131I therapy of thyroid cancer: assessment by micronucleus assay of B lymphocytes.

UNLABELLED: We investigated cytologic radiation damage in thyroid cancer after (131)I therapy using micronucleus assay (MNA) of B lymphocytes exclusively, as opposed to our previous study in which MNA of all lymphocyte subsets was used. METHODS: We studied 22 thyroid cancer patients treated with 3.7 GBq of (131)I. Peripheral lymphocytes were harvested, and B lymphocytes were isolated by an immunomagnetic method and assayed for the frequency of micronuclei. RESULTS: The frequency of micronuclei among B cells after (131)I therapy was significantly increased relative to that in untreated control subjects, and the (131)I-induced increase in micronuclei frequency among B cells was significantly greater than that among all lymphocytes. CONCLUSION: Compared with the MNA of all lymphocytes, the MNA among specifically B cells may more sensitively detect cytologic radiation damage associated with (131)I therapy of thyroid cancer.

Adult↗

Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function.

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

Biomarkers, Tumor↗

Feasibility of 186Re-radioimmunotherapy for treatment in an adjuvant setting of colon cancer.

PURPOSE: (186)Re displays abundant intermediate energy beta emission, and possesses an appropriate physical half-life of 3.7 days. We compared the efficacy of radioimmunotherapy (RIT) with an anti-colorectal cancer monoclonal IgG1, (186)Re-A7, with that of RIT employing (131)I in a mouse liver metastasis model. METHODS: Liver metastases were established by intrasplenic injection of LS180 human colon cancer cells. Based on the results of toxicity assessment with escalated administration doses, 21 MBq (186)Re-A7 and 7 MBq (131)I-A7 were chosen as maximum tolerated doses. In the first experiment, mice underwent RIT at 2 weeks when metastases attain a diameter of several millimeters, and were killed 2 weeks later to assess metastatic burden in the liver. In the second experiment, RIT was conducted at 1 week when metastases of several hundred micrometers in diameter were observed, and survival of mice was examined. RESULTS: (186)Re-A7 RIT inhibited the growth of liver metastases better than (131)I-A7 RIT ( P<0.02). Furthermore, (186)Re-A7 RIT induced better improvement in survival of mice than (131)I-A7 RIT ( P<0.002). (186)Re-A7 RIT caused slightly more severe myelotoxicity in mice, but they eventually recovered. Radiation dose estimation demonstrated a significant advantage of (186)Re-A7 RIT over (131)I-A7 RIT. CONCLUSION: These results support the use of RIT with (186)Re-MAb in an adjuvant setting in cases involving minimal disease.

Animals↗

Local delivery of (131)I-MIBG to treat peritoneal neuroblastoma.

Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine ((131)I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of (131)I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of (131)I-MIBG. Mice were treated with 55.5 MBq of (131)I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of (131)I-MIBG produced significantly higher tumour accumulation than did i.v. injection ( P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered (131)I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of (131)I-MIBG was 59.3+/-3.9 days and 60.6+/-2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of (131)I-MIBG prolonged survival of mice to 94.7+/-17.5 days ( P<0.02 vs untreated controls and mice treated with i.v. (131)I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of (131)I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of (131)I-MIBG in the treatment of peritoneal neuroblastoma.

3-Iodobenzylguanidine↗

Estimation with Tc-99m tetrofosmin SPECT of salvaged myocardial mass after emergent reperfusion therapy in acute myocardial infarction.

OBJECTIVES: The purpose of this study was to validate a new quantitative index of salvaged myocardial mass calculated from Tc-99m tetrofosmin SPECT for evaluating the therapeutic effect of emergent reperfusion therapy in acute myocardial infarction (AMI). METHODS: Tc-99m tetrofosmin SPECT was performed before and after emergent percutaneous transluminal coronary angioplasty (PTCA) in eight patients with AMI. In the pre-PTCA study, Tc-99m tetrofosmin was injected before emergent PTCA. Two weeks after the PTCA, post-PTCA study was performed. As a quantitative index of salvaged myocardial mass, salvaged myocardial volume (SMV) was defined as the difference of myocardial functional volume between the SPECT studies before and after the PTCA. To investigate the clinical significance of SMV, SMV was compared with the grade of therapeutic efficacy determined visually from pre- and post-PTCA SPECT images and clinical parameters, namely peak creatine phosphokinase level (pCK) and the time from the onset of the AMI to reperfusion (RPT). RESULTS: SMV showed a significant correlation with the visual grade of therapeutic efficacy (r = 0.737, p < 0.037) and a trend toward significant correlation with pCK (r = -0.622, p < 0.1). SMVs in early- and late-reperfusion groups (RPT < or = 6 hr and RPT > 6 hr) were 30.0 +/- 14.0 and -6.2 +/- 25.5 ml, showing a greater mean SMV value in the early-reperfusion group (p < 0.07). CONCLUSION: SMV could be used as a quantitative index of salvaged myocardial mass for evaluating the therapeutic effect of emergent reperfusion therapy.

Aged↗

Asialoglycoprotein receptor concentration in tumor-bearing livers and its fate early after their sectorial resection.

UNLABELLED: The aim of the present study was to investigate asialoglycoprotein receptor (ASGP-R) status in tumor-bearing livers and early after their sectorial resection employing 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) dynamic SPECT. METHODS: Ten normal liver controls and 44 liver tumor patients who underwent sectorial hepatectomy were included in the study. 99mTc-GSA dynamic SPECT study was performed 7 +/- 3 d before (pre-operative) and 34 +/- 13 d after surgery (post-operative) in liver tumour patients. Pre- and post-operative parameters including hepatic functional volume and 99mTc-GSA clearance of unit hepatic functional volume, representing ASGP-R concentration, were measured. The sum of functional volume of the sectors uninvolved in hepatectomy was defined as residual functional volume. Subsequently, post-operative change in functional volume (the ratio of post-operative to residual functional volume), post-operative change in 99mTc-GSA clearance of unit hepatic functional volume (the ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional volume) and percent resection of functional volume were calculated. RESULTS: Pre-operative 99mTc-GSA clearance of unit hepatic functional volume in tumor-bearing livers was significantly lower than that in non-tumor bearing control liver. The ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional volume showed marked variation from 0.57 to 2.14, which negatively correlated with the percent resection of functional volume (r = -0.58, p < 0.0001). The ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional volume exhibited a negative correlation with the ratio of post-operative to estimated residual functional volume (r = -0.67, p < 0.0001). CONCLUSION: ASGP-R concentration is reduced in the presence of liver tumor. ASGP-R concentration reveals variable changes early after sectorial resection; the change negatively correlates with percent resection of hepatic functional volume. Post-operative change in ASGP-R concentration negatively correlates with change in functional volume.

Asialoglycoprotein Receptor↗