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Local hyperthermia (HT) may enhance the efficacy of radioimmunotherapy (RIT). However, the optimal timing of HT relative to administration of antibody is unknown. Human colon cancer xenografts (290 +/- 26 mm3) were treated with 4.63 MBq 131I-A7 monoclonal antibody (MAb) anti-Mr 45,000 glycoprotein antigen on colorectal cancer, and HT at 43 degrees C for 1 h was administered at: (A), 2 days after the 131I-A7 injection at the maximum 131I-A7 tumor accumulation (radiation); (B), soon after the 131I-A7 injection aiming to increase the tumor accumulation of 131I-A7 due to HT vascular effects; or (C), 2 days before the 131I-A7 injection in an attempt at injecting 131I-A7 when increased antigen expression could be expected. Specific growth delay (SGD) of tumors was calculated as (Tqtreat-Tqcontrol)/Tqcontrol where Tq was tumor quadrupling time. The biodistribution and intratumoral distribution of 131I-A7 were investigated to explore the mechanism of tumor response among the different HT regimens. HT alone produced some antitumor effect (SGD 1.90 +/- 0.26), which was less effective than RIT (3.11 +/- 0.50). HT soon after 131I-A7 RIT (B) significantly enhanced RIT efficacy (6.57 +/- 0.51, p < 0.0001) whereas neither HT at 2 days after RIT (A) nor at 2 days before RIT (C) did so. Biodistribution study revealed that HT soon after RIT (B) increased the tumor radiation absorbed dose by a factor of 2.4, while HT after RIT (A) did not increase radiation dose and HT before RIT (C) decreased it. Radioluminograms of tumor sections indicated that HT soon after RIT (B) improved the uniformity of 131I-A7 distribution whereas HT after RIT (A) did not and HT before RIT (C) diminished the uniformity of A7 distribution. In conclusion, the best therapeutic efficacy was obtained when HT was combined soon after the initiation of RIT with 131I-A7. The increased tumor radiation absorbed dose and the uniform intratumoral distribution of 131I-A7 were important factors underlying this improvement, and the additive cytotoxicity of HT is suspected to some extent. HT-induced radiosensitization of tumor was not apparent in this model when HT was given 2 days after 131I-A7 MAb.

Cerebral blood flow(CBF) in 34 patients with bilateral chronic subdural hematoma was measured by 99mTc-HMPAO SPECT before operation. The regional CBF was measured in 26 regions of the 10 cortical regions, putamen, thalamus and cerebellar hemisphere on both sides. According to the thickness of subdural hematoma, the thicker hematoma side was measured and examined as the thick hematoma side, and the other side as the thin hematoma side. Thirty four cases with bilateral chronic subdural hematoma were classified into four groups on the basis of clinical symptoms: 13 cases with headache(headache group), 10 cases with hemiparesis(hemiparesis group), 5 cases with tetraparesis(tetraparesis group) and 6 cases with consciousness disturbance or dementia(consciousness disturbance group), and into two groups according to the degree of midline brain shift on MRI: 14 cases of non-shifted group and 20 cases of shifted group. The average CBF of 34 patients in each region indicated a regional CBF reduction in the frontal, parietal and occipital cortices on the thin hematoma side, and in the putamen on the thick hematoma side. In the headache group, the regional CBF reduction on the thin hematoma side was found in the frontal, parietal and occipital cortices compared with the corresponding regions on the thick hematoma side, and in thalamus on the thick hematoma side. In the hemiparesis and tetraparesis groups, there was no statistically significant CBF reduction between the thick and thin hematoma sides. In the consciousness disturbance group, the CBF reduction in whole brain was remarkably significant. By the degree of the midline brain shift, the CBF reductions between the thick and thin hematoma sides were observed. Namely, in the shifted group, the CBF reductions were noted in the frontal, parietal and occipital cortices in the thin hematoma side, and in the putamen in the thick hematoma side. We concluded that the CBF reduction of bilateral chronic subdural hematoma was bilaterally found in the hemiparesis and tetraparesis groups, and which was finally observed in whole brain in the consciousness disturbance group.

A 31-year-old woman visited an out-patient clinic, because of low-grade fever and general fatigue. She was referred to our hospital and admitted for examination of an abnormal shadow which had been found on the chest radiograph. She had experienced faint right lateral chest pain several times on the deep inspirations. Chest radiography showed a mass shadow with calcification in the right lower lung field on the mediastinal side. Chest radiographic computed tomography showed a 6x6 cm tumor in the right lung field. There were low-density areas with septae inside the tumor. Bone scintigraphy showed extremely high uptake of (99m)Tc-HMDP in the tumor. After surgical resection and pathological examination, we concluded that the tumor was an extensively calcified benign hemangioma of the diaphragm.

Purpose: The purpose of this work was to evaluate the ability of breath-hold gadolinium-enhanced three-dimensional (3D) MR angiography to assess the invasion of the pulmonary vein and the left atrium by lung cancer., Method: Gadolinium-enhanced 3D MR angiography was performed in 20 consecutive patients with lung cancer., Results: At two sites with left atrial invasion shown by MR angiography, associated partial resection of the left atrium was performed. At five sites with invasion of the proximal pulmonary vein within 1.5 cm from the left atrium on MR, partial resection of the left atrium was performed at one site, and the pulmonary vein was resected at the intrapericardial portion at three sites. At two sites with invasion of the proximal pulmonary vein 1.5 cm more distal to the left atrium, the pulmonary vein was resected at the extrapericardial portion., Conclusion: Breath-hold gadolinium-enhanced 3D MR angiography is suitable for assessing invasion of the pulmonary vein and the left atrium by lung cancer.

Using direct measurement, we investigated entrance surface doses of patients for routine radiographs in attempt to develop evaluation methods of patient dose in order to establish the guidance level in Japan. To date, patient doses have been evaluated by calculations based on radiographic conditions, or model experiments using phantoms. Their patient doses are then evaluated based on several assumptions. Direct measurement of patient dose is difficult to perform in many patients due to its time requirement, level of expertise required and difficulty in providing an explanation of the procedure to the patient. However, such direct measurement is essential since it incorporates all aspects of radiography from the radiographic equipment used, to the actual conditions of each patient without assumption. In this study, we examined the (1) need for introducing the guidance level, (2) controversial points in the calculation method for patient dose evaluation, (3) evaluation accuracy required for introducing the guidance level, and (4) necessity for a standardized method.

We previously found that the efficacy of radioimmunotherapy (RIT) with (131)I-A7, an IgG(1) against M(r) 45000 glycoprotein on colon cancer, was enhanced by local hyperthermia (HT) or chemotherapy with 5-fluorouracil (5-FU). In this study, we aimed to further enhance its efficacy by combining these three modalities. Human colon cancer xenografts (146 x 12 mm(3)) in Balb / c nu / nu female mice were treated with 9.25 MBq (131)I-A7 i.v. combined with HT (43 degrees C for 1 h) and 5-FU (30 mg / kg / day i.p. for 5 days). Tumor growth delay, (Tq(treated) - Tq(control) )/ Tq(control) where Tq is tumor quadrupling time, in mice treated with RIT + HT + 5-FU was improved to 12.7 from 5.90, 7.55 and 10.1 with RIT alone, RIT + 5-FU and RIT + HT, respectively. Complete response was observed in 4 out of 8 tumors with RIT + HT + 5-FU and 3 out of 10 with RIT + HT. No tumor showed complete response with RIT + 5-FU or RIT alone. 5-FU slightly increased myelotoxicity of RIT, but HT did not affect it. Body weight loss was not enhanced by the combination. These results indicate that the combination of three modalities is a feasible approach to enhance the antitumor efficacy of RIT without serious increase of toxicity.

99mTc-HL91, a hypoxic marker, may be a predictor of tumor response to radiotherapy and an indicator of tumor oxygenation in the course of treatment. In this study, serial changes in 99mTc-HL91 uptake were observed in the normoxic condition in a human bladder cancer cell line exposed to a single dose or a fractionated dose of 10 Gy with an x-ray beam. The uptake per cell increased during cell growth retardation induced by the irradiation. This finding indicates that 99mTc-HL91 uptake is affected by injury to cells due to radiation; it may therefore be difficult to correctly assess the tissue oxygenation status during radiotherapy with 99mTc-HL91.

A rare, benign congenital lymphangioma has been reported to occur frequently in the neck and axilla, but rarely in the retroperitoneal space. We report a case of a retroperitoneal lymphangioma associated with hypoproteinemia caused by protein-loss into the tumor. In this case, lymphoscintigraphy with subcutaneously injected Tc-99m-human serum albumin (HSA) disclosed the communication between the tumor and the lymphatic system, and sequential abdominal scintigraphy with intravenously injected Tc-99m-HSA revealed the protein loss into the tumor. Abdominal scintigraphy with Tc-99m-HSA injected intravenously or subcutaneously is occasionally useful for determining the etiology of hypoproteinemia.

Cerebral blood flow (CBF) measured by 99mTc-HMPAO SPECT before operation was studied in 60 patients with unilateral chronic subdural hematoma. The regional CBF was measured in 26 regions of the fronto-occipital 10 cortices, putamen, thalamus and cerebellar hemisphere on both sides. Sixty cases with unilateral chronic subdural hematoma were classified into four groups on the basis of clinical symptoms: 17 cases with headache (headache group), 34 cases with hemiparesis (hemiparesis group) and 9 cases with consciousness disturbance or dementia (consciousness disturbance group), and into three groups on the basis of the degree of midline brain shift on MRI: 7 cases of mild shift group, 24 cases of moderate shift group and 29 cases of severe shift group. The average CBF in 60 patients in each region indicated that the regional CBF was reduced in frontal, occipital cortices and cerebellum on the non-hematoma side, and in putamen and thalamus on the hematoma side. In the headache group, the regional CBF reduction on the non-hematoma side was found in only frontal and occipital cortices compared with the corresponding regions on the hematoma side. In the hemiparesis group, the regional CBF was reduced in frontal and occipital cortices on the non-hematoma side and in putamen and thalamus on the hematoma side. The part of CBF reduction in both hemispheres was also noted in the hemiparesis group. In the consciousness disturbance group, the CBF reduction was markedly noted in whole brain. The CBF reductions in frontal and occipital cortices on the non-hematoma side and in putamen, thalamus and cerebellum on the hematoma side was not mutually related with the degree of midline brain shift. We concluded that the disturbance of CBF in chronic subdural hematoma was started from frontal and occipital cortices on the non-hematoma side observed in the headache group, and which was extended to putamen and thalamus on the hematoma side and a part of both hemispheres observed in the hemiparesis group. And such disturbance was finally observed as the CBF reductions in whole brain in the consciousness disturbance group.

Purpose: The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated., Methods: Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) (131)I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg(-1)day(-1) for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy., Results: The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 +/- 9.59 days to 31.3 +/- 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU., Conclusion: The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

Unlabelled: Preoperative assessment of residual hepatic functional reserve offers important strategic information for hepatic resection. To predict the postoperative residual liver function, we assessed the value of hepatic 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) clearance estimated by dynamic SPECT analysis., Methods: We investigated 114 consecutive patients with liver disease, including 55 hepatectomy cases. One minute after injection of 185 MBq 99mTc-GSA, 15 serial dynamic SPECT images were obtained every minute. The initial five sets of SPECT images were analyzed by Patlak plot to estimate the sequential initial hepatic 99mTc-GSA clearance (mL/min) as an index of hepatic function. The sum of hepatic 99mTc-GSA clearance of the segments immune from resection was categorized as predicted residual 99mTC-GSA clearance. In the hepatectomy cases, scintigraphy was performed before and 37 +/- 10 d after the operation., Results: Good correlation was observed between the total hepatic 99mTc-GSA clearance and conventional hepatic function tests: plasma retention rate of iodocyanine green (ICG) at 15 min (ICG R15), r = -0.600, P < 0.0001, n = 94; plasma disappearance rate of ICG (K ICG), r = 0.670, P < 0.0001, n = 83; cholinesterase, r = 0.539, P < 0.0001, n = 121; serum albumin, r = 0.421, P = 0.0001, n = 123; and hepaplastin test, r = 0.456, P < 0.0001, n = 120. There was good correlation between the predicted residual 99mTc-GSA clearance and the postoperative total hepatic 99mTc-GSA clearance in patients who underwent segmentectomy or lobectomy (r = 0.84, P < 0.0001, n = 28) and between the pre- and postoperative total hepatic 99mTc-GSA clearance in patients who underwent subsegmentectomy (r = 0.91, P < 0.0001, n = 25). Five patients who had postoperative complications due to hepatic insufficiency (2 patients died of postoperative hepatic failure within 2 mo after operation) showed significantly lower predicted residual 99mTc-GSA clearance compared with the patients without complications (90.3 +/- 37.2 versus 320.9 +/- 158.8 mL/min; P < 0.005)., Conclusion: The total hepatic 99mTC-GSA clearance reflected hepatic function. In addition, preoperative predicted residual hepatic 99mTc-GSA clearance was a good indicator of postoperative hepatic function and early prognosis. 99mTc-GSA dynamic SPECT is assumed to be a useful method for determining the surgical strategy in patients with hepatic tumor and especially in patients with hepatic dysfunction.

A 67-year-old man presented with malaise and marked anemia. A diagnostic workup revealed severe pancytopenia on a complete blood count and diffuse sclerotic change in the axial skeleton on a plain abdominal radiograph. Bone metastases being suspected from these findings, bone scintigraphy was performed. The bone scan demonstrated uniformly increased skeletal activity with faint soft-tissue activity. The findings of the bone scan, however, appeared atypical of the super scan caused by diffuse bone metastases, without any decrease in radioactivities of the appendicular skeleton and kidneys. Bone marrow scintigraphy with In-111 chloride demonstrated central marrow failure and peripheral expansion, which indicated the possibility of myelophthisis. The patient underwent bone marrow biopsy, which revealed replacement of the bone marrow by metastatic adenocarcinoma. Further examinations detected the primary lesion in the prostate. In this case, the findings of the bone scan were insufficient for the super scan, and might be categorized as a sub-super scan. It would be important to recognize this incomplete form of super scan as a rare scintigraphic pattern of diffuse bone marrow metastases.

A 68-year-old man with pneumoconiosis was thought to have small-cell lung cancer based on the results of a biopsy of a bone tumor. Three pulmonary nodules were observed on a chest radiograph. Compared with a chest radiograph taken 4 months earlier, one of the nodules had grown. It was difficult to differentiate this nodule from pneumoconiosis-related benign pulmonary nodules from the appearance on the chest radiograph and CT. Ga-67 scintigraphy and TI-201 lung SPECT were performed to characterize these nodules. TI-201 SPECT showed differential high uptake in the enlarged nodule, whereas Ga-67 scintigraphy showed equally intense uptake in all these nodules. Transbronchial biopsy of the nodule that showed high TI-201 uptake revealed cancer cell nests against a background of interstitial fibrosis. The pathologic diagnosis was small-cell lung cancer that had developed in lung scar tissue. This case suggests the utility of TI-201 in scintigraphic assessments of pneumoconiosis-related pulmonary nodules when lung cancer is suspected.

A 69-year-old man had hypothyroid dementia as a result of I-131 therapy and an overdose of methimazole. Tc-99m HMPAO SPECT revealed diffuse cerebral hypoperfusion. The findings of brain SPECT normalized with the disappearance of symptoms and a return to the euthyroid state. There was a 25% or 26% reduction of the mean cerebral blood flow during dementia. This may be the first report in which SPECT brain imaging revealed reversible hypoperfusion associated with reversible hypothyroid dementia.

Epidemiological studies recently have indicated that magnetic fields and radiofrequency (RF) radiation have an adverse influence on the living body. The purpose of this study was to examine the safety of magnetic resonance imaging (MRI) by observing whether bacterial mutation occurs in an approximate MRI environment. We employed a GX-270 FT-NMR unit (JEOL, Ltd.) with a magnetic field strength of 6.3 Tesla. The Salmonella typhimurium tester strains used in the AMES test were exposed, and the incidence of point and frameshift mutations was evaluated. TA98 and TA7001-7006 mixed strains were used to detect frameshift and point mutations, respectively. Tester strains were exposed to the 6.3 Tesla magnetic field with RF radiation (90 degrees and 180 degrees refocusing pulses were repeated using the hydrogen Lamor frequency at 2-second intervals) for 15, 30, 45, and 60 minutes. After each exposure, the rate of revertant mutation was counted. The rates of revertant mutation in mixed strains and the TA98 strain were not statistically significant. Therefore, it was concluded that bacterial mutation is not increased by RF radiation under a 6.3 Tesla magnetic field.

Experimentally we investigated the detection of lung cancer with N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP). Various tumors including Lewis lung cancer were used as tumor models. Serial images were obtained. Biodistribution of Lewis lung cancer was performed. In Lewis lung cancer good visualization as in B-16 melanoma and high tumor accumulation were found with IMP. In conclusion, due to its greater accumulation almost equivalent to that in melanotic melanoma, I-123 IMP may have a role in the detection of lung cancer.

The uptake and retention of single photon tracers in irradiated tumour cells was observed in an attempt at the early evaluation of the effect of radiation. T24 human bladder cancer cells were exposed to a single dose of 10 Gy or 20 Gy or a fractionated dose of 10 Gy (2 Gy for 5 days). The uptake of 201Tl chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin was observed by incubating in vitro for 60 min. The retention of the tracers was observed at 60 min after changing the incubation medium for a tracer-free medium. Uptake per culture well of all tracers in the cells exposed to 20 Gy declined as viable cell number decreased, but uptake per cell increased progressively. Uptake per cell of all tracers in the cells exposed to either a single dose or a fractionated dose of 10 Gy also increased, while a delay in growth was observed. The retention of these tracers decreased during this period and recovered thereafter. A binding assay with purified human leukocytes indicated that assessment with 99Tcm-sestamibi and 99Tcm-tetrofosmin is influenced by inflammatory cells. In conclusion, the effect of radiation may be underestimated if assessed by tracer uptake alone because of the increase in tracer uptake in viable irradiated cells. Observation of the retention of tracers may provide additional information.

Hyperthermia (HT) may increase tumor targeting of a radiolabeled antibody by its effects on tumor vasculature and antigen expression. Expression of a 45-kDa glycoprotein antigen on LS180 colon cancer cells was 2.7-fold enhanced 2 days after heating at 43 degrees C for 1 h. Preferential tumor accumulation of 125I-A7 recognizing this antigen was doubled and the antitumor effect of 131I-A7 was significantly improved by HT. Hyperthermia also increased tumor uptake of an irrelevant antibody but its radioactivity was rapidly cleared. These results indicate that HT increased the initial delivery of an antibody to a tumor by its vascular effect, and radioactivity was retained in tumors by increased specific binding, resulting in a better radioimmunotherapy outcome.

Purpose: To evaluate the indication and advantages of venous sac embolization of pulmonary arteriovenous malformations (PAVMs) using interlocking detachable coils (IDCs)., Methods: We performed percutaneous embolization in 12 PAVMs in four patients using IDCs, initially placed in the venous sac or at the feeding artery to prevent systemic migration of additional coils. We placed the IDCs in the venous sac in PAVMs with the following vascular architecture: the draining vein was larger than the feeding arteries and both vessels were interposed with the venous sac or there were short feeding arteries., Results: Complete occlusion was achieved in all 12 PAVMs without significant complications. We deployed IDCs in the venous sac in eight PAVMs and in the feeding artery in four., Conclusion: Venous sac embolization may be beneficial in PAVMs with large out-flow vessels or short feeding arteries. IDCs are suitable for this procedure.

Phase III clinical study in 78 patients with hyperparathyroidism was performed to determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning parathyroid lesions. Except slight tremor in one patient, no adverse events were reported. No abnormal changes in clinical laboratories or vital signs were noted. The clinical utility of the agent was evaluated in 70 patients. Out of 108 hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of their histology, numbers, or location. Specifically, single or ectopic lesions were detected with high sensitivity (97% and 100%, respectively). Sensitivity in 53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is extremely high compared to the 201T1-99mTc subtraction method. Specificity in a group of PHP patients with single adenoma who underwent surgery was 100% (63/63), though in case of coexistent thyroid disease obviously interfered parathyroid images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of hyperfunctioning parathyroid tissues. Especially, the fact that 99mTc-MIBI detected ectopic glands with high specificity is a great advantage over the ultrasound or 201Tl-99mTc subtraction method.

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.

Stability and immunoreactivity of 186Re-labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor-bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A murine IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re-MAG3 complex was conjugated to A7 after esterification of 186Re-MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively. Immunoreactivity of purified 186Re-MAG3-A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re-MAG3-A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at -80 degrees C could effectively prevent the radiolysis of 186Re-MAG3-A7 for 7 days. Immunoreactivity of 186Re-MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after the preparation. In colon cancer xenografted mice, 31.0% of the injected dose/g of 186Re-MAG3-A7 had accumulated in the tumors at 24 h postinjection. Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12-fold greater than the whole-body radiation dose. These in vivo characteristics were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131I-A7. Because of the better image quality of 186Re-MAG3-A7 as well as more favorable dosimetry, 186Re-MAG3-A7 would be a better choice for RIT of colon cancer than 131I-A7. These results indicated the feasibility of RIT with 186Re-MAG3-A7, though the prevention of radiolysis of the labeled antibody should be considered.

The diagnostic value of Tc-99m leukocyte imaging for evaluating disease activity and monitoring treatment response in ulcerative colitis was compared with that of colonoscopy. A total of 48 studies were performed in 28 patients with ulcerative colitis. Forty-six studies had both Tc-99m leukocyte imaging and colonoscopy within 2 weeks of each other, and the remaining two studies had only Tc-99m leukocyte imaging. In 46 studies, semiquantitative grading of colonic radioactivity by comparison with iliac crest marrow activity on radionuclide imaging correlated well with macroscopic grading based on Matts' criteria on colonoscopy. Fourteen (82%) of 17 studies with slight colonoscopic change showed a negative result on the radionuclide image. In 15 patients treated with glucocorticoids or leukapheresis, radionuclide imaging showed nearly the same statistical results as colonoscopy in monitoring treatment response. Tc-99m leukocyte imaging could be used as an alternative to colonoscopy to evaluate the disease activity of ulcerative colitis or to monitor the treatment response, although it is insensitive for detecting disease with only slight macroscopic changes.

A 19-year-old man with a double-chambered right ventricle (DCRV) and an associated ventricular septal defect was admitted to the hospital for surgical correction. Preoperative study of myocardial perfusion with Tc-99m tetrofosmin SPECT depicted the two chambers of the right ventricle. There was a substantial differential in the radioactive uptake between these two chambers. The inflow and outflow chambers with different peak-pressures (94 and 18 mm Hg) showed different uptakes reflecting the pressure difference, which was intense in the inflow chamber and weak in the outflow.

To obtain both hepatic blood flow and an index of asialoglycoprotein receptor amount by simple calculation in the asialoglycoprotein receptor imaging with 99mTc-DTPA-Galactosyl Human Serum Albumin (99mTc-GSA), we have tested the applicability of the direct integral linear least square regression (DILS) method based on a linear 3-compartment model (Bronqvist, 1984) to the kinetic analysis of 99mTc-GSA scintigraphy. DILS method can provide hepatic blood flow (k1) and the product of receptor amount and forward binding rate constant (k1k3/k2) as a receptor index, without requiring iterative calculation and initial estimates of the parameters. To compare DILS method with nonlinear least square regression (NLS) method as a standard, data from 35 patients with liver dysfunction were analyzed by both methods. The effect of the data noise to parameter estimate were simulated, and both DILS and NLS method could provide reliable parameter estimate which is relatively insensitive to the data noise. In estimated model parameters, both hepatic blood flow (k1) and the receptor index (k1k3/k2) showed significant correlation between 2 methods (r2 = 0.96, p < 0.0001; r2 = 0.99, p < 0.0001, respectively). We concluded that DILS method was comparable to NLS method in determination of the model parameters and could be useful in the asialoglycoprotein receptor imaging.

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.

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

We report discordant splenic uptake of Tc-99m colloid and Tc-99m heat-denatured red blood cells (RBC) which occurred in a 21-year-old female with candidiasis-endocrinopathy syndrome. Tc-99m colloid liver-spleen imaging showed no splenic uptake, suggesting the presence of functional asplenia. A subsequent Tc-99m heat-denatured RBC study clearly revealed a small spleen with preserved sequestrating function. These results may demonstrate that the qualitative dissociation of splenic functions in processing colloid and denatured RBC in functional asplenia: the sequestration function remains while the reticuloendothelial system is impaired.

We retrospectively reviewed the records of 11 thymoma patients to clarify the role of hemithoracic irradiation and chemotherapy for patients with thoracic dissemination at the initial presentation. Radiotherapy was administered postoperatively in all but two patients who were not candidates for surgical treatment. Radiotherapy doses ranged from 10 to 17 Gy for the entire hemithorax of the disseminated site and from 30 to 55 Gy to the primary tumor bed. Chemotherapy of various protocols was also employed preceding radiotherapy in seven cases. Cumulative 5- and 10-year survival rates were 80% and 64%, respectively. Regrowth-free 5- and 10-year survival rates were 55% and 37%, respectively. Six of the 11 patients were free from regrowth at a median follow-up interval of 60 months. The role of chemotherapy remained unclear. Acute or late sequelae were modest and acceptable. In conclusion, entire hemithoracic irradiation is justified as postoperative or definitive radiotherapy treatment for disseminated thymoma unless there is a risk of radiation pneumonitis. Further evaluation should be conducted.

We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum 123I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of 123I-MIBG was significantly high respectively compared with normal subjects (n = 8). H/M was negatively correlated with serum norepinephrine level, wall thickness of left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, 123I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM.

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.

In herpes simplex encephalitis (HSE), the authors noted an evident dissociation between the 99mTc-ethyl cysteinate dimer (ECD) and 99mTc-d,l-hexamethyl-propylene-amine oxime (HMPAO) single photon emission computed tomographies (SPECTs). The patient was a 5-year-old boy with diffuse type of pontine glioma, which was treated with hyperfractionated radiotherapy. Two weeks after the completion of radiation therapy, a lesion suggesting that of HSE was noted in the right fronto-temporal region on magnetic resonance images. 99mTc-HMPAO SPECT showed an increased accumulation of the tracer in this lesion. On the 99mTc-ECD dynamic SPECT, an exaggerated accumulation of the tracer was noted within 80 s of administration, followed by a rapid drop in the accumulation, resulting in a low accumulation in 10 min. It was assumed that this dissociation was due to the different mechanisms to trap HMPAO and ECD in the brain tissue.

Wilms' tumor (nephroblastoma), the most common renal neoplasm in children, is rarely found in adults. A 73-year-old woman with asymptomatic adult Wilms' tumor, incidentally detected by CT, is reported. CT and MRI showed a small mass with homogeneous enhancement after the administration of contrast medium. Ultrasonography demonstrated a well-defined echogenic mass with a halo-like, peripheral hypoechoic area. Selective angiography showed no tumor vessels. Although renal cell carcinoma should be considered in the differential diagnosis, it is still difficult to distinguish from small Wilms' tumor like this case.

We synthesized a radiosensitizer KADTF, consisting of a hypoxic radiosensitizer, KU2280, bound to the side chain group of Mn-metalloporphyrin, which accumulates in tumor tissue. In the in vitro colony-forming activity test using HeLa cells, KADTF enhanced the effect of radiation under hypoxic conditions. Radiation therapy at 20 Gy, 1.5 h after infusion of KADTF (0.15 mM/kg), inhibited tumor growth more markedly than did a single radiation treatment. A clear tumor MR images of the SCCVII tumor was obtained at 1.5 h after administration of KADTF (0.1 mM/kg).

We examined a series of 21 peripheral facial palsy patients attempted to (17 Bell's palsy, 4 Hunt syndrome) with Gd-DTPA-enhanced MRI and attempted to determine the relation between prognosis and MRI findings. We divided patients into two groups based on facial palsy scores of Japanese facial nerve research: a good group (G-Group) and a bad group (B-group). The G-group scored over 20 points on the 20th day after the first visit and the B-group under 20 points. G-group consisted of 9 Bell's palsy and 1 Hunt syndrome patients, and the B-group of 8 Bell's palsy and 3 Hunt syndrome patients. The averaged facial palsy score of both groups was analyzed every week during 4 weeks. Recovery from the palsy was better in the G-group than the B-group (P < 0.05); the scores at the 4th week of the G- and B-groups were 32.6 +/- 15.2 and 7.8 +/- 7.4, respectively. The MRI findings of both groups were examined retrospectively. Nine of 10 G-group and nine of 11 B-group patients had abnormal contrast enhancement. The result of enhanced facial nerve segment was as follows:G-group, auditory canal 1, labyrinthine/geniculate 7, tympanic 7, mastoid 7; B-group, auditory canal 2,labyrinthine/geniculate 8,tympanic 8, mastoid 7. Our results indicate no relation between the prognosis and the MRI findings. Therefore, it is impossible to predict the prognosis of facial palsy from the results of Gd-DTPA-enhanced MRI.

A patient with neuro-Behçet's disease was studied with both Tc-99m-HMPAO and Tc-99m-ECD brain perfusion SPECT during the same time period. In Tc-99m-HMPAO SPECT, focal high uptake was observed in the left basal ganglia where MRI depicted abnormal signal intensity. Conversely, Tc-99m-ECD SPECT did not show corresponding high uptake, but demonstrated rather low uptake in contrast to the Tc-99m-HMPAO SPECT. This case suggests that Tc-99m-HMPAO and Tc-99m-ECD may show discordant distribution in inflammatory brain disease such as neuro-Behçet's disease.

Inflammatory imaging using 99mTc-HMPAO-labeled mixed leukocytes was assessed for use in treating 11 cases diagnosed as ulcerative colitis: 10 cases with total colitis and 1 with left-sided colitis. They consisted of 8 patients with relapse-remitting type and 3 with chronic continuous type. Radionuclide abdominal images were obtained at 1 hr, 4 hr and 24 hr after intravenous injection of 200 MBq prepared 99mTc leukocytes. Obvious colonic activity noted at 4 hr served as the basis for positive comparative criterion in the present study. The diagnostic efficacy of radionuclide imaging was compared with endoscopic findings (based on Matts' classification) and the clinical manifestations as reference. The sensitivity and specificity of this imaging were 83.3% and 85.7%, respectively, these values being consistent with endoscopic findings and clinical manifestations at sites of disease activity. All of positive images changed to negative after treatment by leukocyte apheresis or glucocorticoid. Based on these results, 99mTc leukocyte imaging can be used to accurately evaluate severity and treatment response in ulcerative colitis. Leukocytes may be closely related to the pathogenesis of ulcerative colitis.

We studied 50 patients with mild to moderate renal dysfunction to compare pharmacokinetics of 99mTc-MAG3 with that of 131I-OIH. After simultaneous bolus injection of both 99mTc-MAG3 and 131I-OIH, 8-point venous blood sampling was performed from 2 to 44 min post injection. Aliquoted plasma samples were counted for radioactivity along with the injected standard to obtain % injected dose/ml plasma for each tracer. Using obtained time-concentration data, classical 2 compartment model analysis was performed for both tracers to obtain various pharmacokinetic parameters, including distribution volumes (Vds), inter-compartmental rate constants, and plasma clearance. In these parameters, Vd of central compartment, Vd at steady state, central to peripheral inter-compartmental rate constant, and plasma clearance were significantly larger for 131I-OIH. In all parameters, significant correlation was found between 99mTc-MAG3 and 131I-OIH. The best correlation was seen in plasma clearance (r = 0.891, p < 0.0001). Plasma clearance ratio (99mTc-MAG3/131I-OIH), however, showed weak but significant negative correlation with serum creatinine, although this correlation was not likely to affect the overall correlation of clearance between 131I-OIH and 99mTc-MAG3. From these results, we confirmed that 99mTc-MAG3 clearance could be used as an alternative to 131I-OIH clearance, although pharmacokinetic behavior of 99mTc-MAG3 was not exactly the same as that of 131I-OIH.

We retrospectively reviewed the case histories of 45 patients with invasive thymoma who underwent postoperative or definitive radiotherapy. Patients in stage II or stage III were classified according to the treatment volume as follows: a) those who received irradiation confined to the primary tumor site with a generous margin (involved field group, n = 17) and b)those who received prophylactic whole mediastinal irradiation with or without entire hemithoracic irradiation (prophylactic group, n = 21). Seven recurrences were observed among the involved field group, while all patients in the prophylactic group were relapse-free and alive after a median follow-up interval of 50 months. Major side effects were observed in two patients who received entire hemithoracic irradiation. One developed severe pneumonitis resulting in lung fibrosis that required hospitalization, while the other developed nephrotic syndrome of unknown cause. We conclude that whole mediastinal irradiation with or without entire hemithoracic irradiation can be used as a treatment of choice for postoperative invasive thymoma.

Forty-one patients with non-hodgkin's lymphoma at stages I and II who had received radiation therapy were reviewed to analyze the prognosis and prognostic factors, with the main focus on a comparison of elderly (age > 65 years) and younger patients. In terms of clinical and histological characteristics, there were no differences between the elderly and younger patients. The 5-year-survival rate (5YS) in elderly patients was 52.8%, compared with 68.6% for younger patients. In patients treated with irradiation alone, the 5YS was 49.5% in elderly patients and 22.1% in younger patients. Combination treatment consisting of irradiation and chemotherapy improved 5YS markedly to 84.9% in the younger patients, while no apparent improvement was seen in the elderly patients, in whom 5YS was 54.1%. Using Cox's multiregression life table, two prognostic factors, the presence of symptoms and LDH, were extracted and found to have a significant influence upon the survival of the elderly patients. Complete response was 90.2% in the elderly patients, although relapse was seen in 54.1% of the complete responders. Relapse occurred overwhelmingly outside the irradiated regions. Since the prognosis of elderly patients could not be improved with the current chemotherapy regimen, some different regimen must be established to lower the high relapse rate in the area outside the irradiated field.

We report two cases of alveolar echinococcosis (AE) of the bone, and present the computed tomography (CT) and magnetic resonance (MR) imaging findings of these surgically proven cases of AE of the ilium and clavicle. CT and MR imaging showed destruction of the ilium and clavicle, and numerous cysts of the bone and surrounding tissues. Moreover, CT and MR imaging clearly demonstrated spread of the parailiac region and superior mediastinum. CT and MR imaging were very useful in determining the extent of surgery. Our experience suggested that CT and MR imaging are complementary studies.

Presently, radionuclide imaging in hepatobiliary disease is mainly used to evaluate the functional aspect in hepatobiliary disease. For the evaluation of hepatic function, three kinds of radiopharmaceuticals are now commercially available: these are the Kupffer-cell oriented radiotracer of 99mTc-colloid, the hepatocyte oriented radiotracer of 99mTc-PMT, and the receptor-binding radiopharmaceutical of 99mTc-GSA. These radiopharmaceuticals must be properly used, according to the purposes. 99mTc-PMT can be used to determine the degree of functional disorder in acute hepatic disease and evaluate the severity of diffuse hepatic disease, whereas 99mTc-colloid can effectively evaluate the potential etiology of the disease process and its chronicity. And 99mTc-GSA may also be used to evaluate the severity of the disease. In particular, the hepatic functional reserve must be evaluated with 99mTc-GSA. The biliary patency from the intrahepatic bile canaliculi to the common bile duct can be effectively evaluated with 99mTc-PMT. The diagnosis of acute cholecystitis is most reliably made by radionuclide imaging. And radionuclide imaging is sometimes to be used for the differentiation of cholestasis. In particular, the discrimination among the disease entities of chronic intermittent intrahepatic cholestasis including primary biliary cirrhosis, primary sclerosing cholangitis and juvenile intrahepatic bile duct hypoplasia can be made. Moreover, it is also be used in evaluating constitutional hyperbilirubinemia, biliary leakage, infantile jaundice and gallbladder or syphinctor Oddi motor dysfunction.