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Seigo Kinuya

Publications and source records attributed to Seigo Kinuya.

At least 37 records · Page 2Linked to original sources

Single dose planning for radioiodine-131 therapy of Graves' disease.

OBJECTIVE: Patients with Graves' disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used. METHODS: Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. RESULTS: No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. CONCLUSIONS: No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed.

Adult↗

227Th-EDTMP: a potential therapeutic agent for bone metastasis.

The biodistribution of 227Th-EDTMP and retention of its daughter nuclide 223Ra were examined. 227Th-EDTMP was found to show high uptake and long-term retention in bone. The clearance of 227Th-EDTMP from blood and soft tissues was rapid and the femur-to-tissue uptake ratios reached more than 100 within 30 min for all tissues except the kidney. Seven and 14 days after injection of 227Th-EDTMP, the retention index of 223Ra in bone showed high values, and the differences between these time points were not significant. Therefore, 227Th-EDTMP is a potential radiotherapeutic agent for bone metastasis.

Animals↗

Role of brain perfusion single-photon emission tomography in traumatic head injury.

This investigation examined the role of brain perfusion single-photon emission tomography (SPET) in traumatic head injury in 35 patients. The results were compared with those of X-ray computerized tomography (CT) and magnetic resonance imaging (MRI). CT and MRI detected brain contusions in seven patients, subarachnoid haemorrhage in one patient and both in nine patients. In 16 of the 17 subjects (94%), SPET with technetium-99m-hexamethylpropyleneamine oxime (Tc-HMPAO) revealed CT/MRI-negative abnormalities, such as hypoperfusion in the contre-coup region, frontal hypoperfusion related to personality change and cerebellar hypoperfusion associated with vertigo. In two patients presenting with diffuse axonal injury in the brainstem, hypoperfusion in the frontal cortex on the affected side was observed on SPET. SPET demonstrated hypoperfusion in the adjacent cortex, with no abnormality on either CT or MRI, in six of seven patients exhibiting acute epidural haematoma. SPET failed to provide additional information in two of five patients with acute subdural haematoma and in one of two patients displaying chronic subdural haematoma. In four of nine patients with post-traumatic amnesia, SPET detected hypoperfusion in the temporal lobe, with no abnormality on either CT or MRI. In five of eight patients with vertigo, SPET detected hypoperfusion in the morphologically normal cerebellum. In seven cases involving personality change, frontal hypoperfusion was observed in four; moreover, a markedly non-homogeneous pattern was evident in the remaining three. Overall, SPET afforded additional information in 26 patients (74%). CT possesses an advantage with respect to the detection of haemorrhagic lesions. MRI provides more precise information regarding contusions and axonal injury. Frequently, SPET may be the only examination to reveal perfusion abnormalities which are related to symptoms in the absence of other objective findings, such as post-traumatic amnesia, vertigo or personality change.

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↗

Detection of cardiomyocyte death in a rat model of ischemia and reperfusion using 99mTc-labeled annexin V.

UNLABELLED: There is increasing evidence that cell death after myocardial ischemia and reperfusion may begin as apoptosis rather than necrosis. To determine the time course, location, and extent of this process, we studied groups of rats after a 20-min interval of coronary occlusion and reperfusion. METHODS: After thoracotomy, the left coronary artery was occluded for 20 min. After release and before study, groups of animals were allowed to recover for various intervals: 0.5 h (n = 6), 1.5 h (n = 7), 6 h (n = 7), 1 d (n = 8), 3 d (n = 8), or 2 wk (n = 5). At the time of study, the rats were injected with 99mTc-annexin V (80-150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess 99mTc-annexin V uptake and the area at risk. RESULTS: Extensive 99mTc-annexin V uptake was observed in the mid myocardium after 0.5-1.5 h of reperfusion. The area of annexin uptake had expanded in the subendocardial and subepicardial layers at 6 h after reperfusion and then gradually lessened over 3 d. At 0.5 and 1.5 h of reperfusion, 99mTc-annexin V uptake ratios were 7.36 +/- 2.95 and 6.34 +/- 2.24 (mean +/- SD), respectively. The uptake ratios gradually decreased at 6 h, 1 d, 3 d, and 2 wk after reperfusion (4.65 +/- 1.93, 3.27 +/- 0.92 [P < 0.01 vs. 0.5 h], 1.84 +/- 0.55 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], and 1.65 +/- 0.31 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], respectively). CONCLUSION: These data indicate that annexin binding commences soon after ischemia and reperfusion in the mid myocardium within the area at risk and expands to include the subendocardial and subepicardial layers at 6 h after reperfusion, followed by gradual reduction of activity over 3 d.

Animals↗

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↗

Thallium-201 brain SPECT to diagnose aggressiveness of meningiomas.

This investigation was conducted to determine the ability of 201Tl brain SPECT with respect to preoperative prediction of lesional aggressiveness of meningioma. Fifty-nine lesions in 42 patients were examined. Early (15 min) and late (3 h) SPECT were obtained. Early uptake ratio (ER; lesion to normal brain average count ratio), late uptake ratio (LR) and the ratio of LR to ER (L/E ratio) were calculated. Twenty-three lesions exhibited malignant features based on histologic or clinical course such as recurrence or skull invasion. Both ER and LR of malignant meningiomas were significantly higher than those in thirty-six benign lesions. Benign lesions were classified into two groups for further analysis: meningotheliomatous type, which is the most common histology, and benign lesions other than the meningotheliomatous (other benign) type. ER in other benign type was lower than the meningotheliomatous and the malignant type. LR afforded differentiation of the malignant type from the two benign types. These two benign types could be distinguished on the basis of the L/E ratio. These results indicate that high pre-operative ER and LR values in patients with meningioma are indicators of the aggressiveness of lesions, i.e., malignant meningioma, recurrence or skull invasion.

Brain Neoplasms↗

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↗

Discrepant uptake between fluorine-18 fluorodeoxy glucose and Tc-99m sestamibi in bronchioloalveolar cell carcinoma.

Several studies have shown the benefit of fluorine-18 fluorodeoxy glucose (FDG) imaging in the differentiation of solitary pulmonary nodules. The majority of malignant tumor have a higher glucose metabolic rate as compared to benign lesions. However, there is a considerable variety in glucose metabolic rate that depends on the aggressiveness and histological subtype of the tumor. Technetium-99m sestamibi (MIBI) is another tumor imaging agent for SPECT. We present a case of bronchioloalveolar cell carcinoma with a false negative finding in FDG imaging and a positive finding in MIBI imaging. This case clearly indicates that the FDG uptake and MIBI uptake might provide different information regarding characteristics of lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗

Preliminary evaluation of image reconstruction by ordered-subset expectation maximization in thallium-201 lung scintigraphy.

OBJECTIVES: We observed whether clearer tumor delineation and greater tumor to non-tumor (T/N) count ratios could be obtained using an iterative ordered-subsets expectation maximization (OSEM) algorithm than conventional filtered-back projection algorithm (FBP) in the image reconstruction of thallium-201 (201Tl) lung scintigraphy. METHODS: In 29 patients with lung cancer and phantom studies, tomograms were reconstructed using FBP and OSEM algorithms, with and without a prefilter (Butterworth filter: BW), whose cut-off frequencies were 0.10 cycles/pixel for FBP and 0.10 and 0.17 cycles/pixel for OSEM. Visual interpretation and tumor to non-tumor (T/N) count ratios were obtained and compared. RESULTS: Without a prefilter, T/N ratios from OSEM and FBP were 1.89 +/- 0.31 (early) and 2.00 +/- 0.54 (late) for OSEM, 1.90 +/- 0.33 (early) and 2.05 +/- 0.59 (late) for FBP, respectively. The OSEM reconstruction without prefiltering showed clearer tumor contours than FBP without a prefilter. Incorporation of BW showed visually low-noised images but decreased T/N ratios in both reconstructions with BW (0.10 cycles/pixel). No greater T/N ratios were obtained by OSEM than FBP, with or without prefiltering. With BW with a cut-off frequency of 0.17 cycles/pixel, the same T/N ratios as those without BW were obtained. The tumor model sized 0.9 cm in the phantom study was invisible in both OSEM and FBP reconstructions without a prefilter, but visible with a prefilter. The influence of prefiltering on T/N ratios was also observed in phantom studies. CONCLUSIONS: Visually improved tumor delineation could be obtained in OSEM reconstruction without a prefilter as compared to FBP reconstruction without a prefilter for tumors greater than 2 cm. Prefiltering should be incorporated into OSEM reconstruction in diagnosing small tumors. However, the influence of prefilter (BW) setting on semi-quantitative interpretation needs further discussion.

Adult↗

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↗

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↗

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↗

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↗

Radionuclide cisternography in intracranial hypotension syndrome.

A 44-year-old male patient complaining of severe headache right after twisting his body during aerobic exercises in a swimming pool underwent In-111 DTPA radionuclide cisternography. Leakage of cerebrospinal fluid (CSF) was proved on the right side of T2 and T3 vertebrae. Cisternography after bed and conservative treatments demonstrated the disappearance of abnormal tracer accumulations. Radionuclide cisternography is of great value in diagnosing cerebral-spinal fluid leak and in evaluating the therapeutic effect.

Adult↗