Bsh distributions in the canine head and a human patient using 11b mri

A 3D projection reconstruction (3DPR) method was used to obtain in vivo ¹¹B images in a large canine brain tumor model and in a human infused with borocaptate sodium (BSH). Studies were performed in dogs with and without gliosarcomas implanted and grown to a size of 2–3 cm. The 3DPR method demonstrates a signal-to-noise ratio (SNR) that allows qualitative kinetic studies of the boron compound in normal and tumor tissue of the head. The measurements indicate initial uptake of the BSH compound in tumor to be less than that in muscle with no uptake in normal brain tissue. Moreover, uptake of BSH in tissue was found to lag the boron concentration in blood with delays that depend on tissue type. In addition, the first human boron images were obtained on a patient who underwent surgical resection and volumetric debulking of a large (7 cm) glioblastoma multiforme. BSH was readily taken up in residual tumor tissue, while diffusion into the resection volume was slower.     

Pretreatment with buthionine sulfoximine enhanced uptake and retention of BSH in brain tumor

To determine the influence of buthionine sulfoximine (BSO) on boron biodistribution after sulfhydryl borane (BSH) administration for boron neutron capture therapy, the effectiveness of the combination of BSO with sulfhydril- (BSH) and non-sulfhydril (B₁₂H₁₂ and BNH₃) boron compounds, and the interval between BSO and BSH administration, the retention of boron in tissues have been evaluated using a 9L rat tumor model. Simultaneous administration of BSH and BSO showed significantly higher boron accumulation compared to that without BSO, however there was no difference in tissue boron level between B₁₂H₁₂ and BNH₃ administration with BSO or without BSO. The longer interval (6 h) between BSH and BSO administration related to the highest boron concentration in the brain and subcutaneous tumors compared to shorter intervals (0.5, 3 h). Boron concentration in subcutaneous and brain tumors was maintained for 6 and 12 h after the administration of BSH following BSO pretreatment.     

Changed delivery of boron to tumours using electroporation for boron neutron capture therapy with BSH

For effective boron neutron capture therapy (BNCT) it is important that a sufficient concentration of boron (10B) is present in the tumour during irradiation. This requirement represents a specific problem. The aim of this study was to test whether electroporation can be used as a non-specific drug delivery system to increase the delivery of sodium borocaptate-10B (BSH) into MCF7 (breast carcinoma) and B16F1 (melanoma) tumour cells in vitro and in B16F1 tumours in vivo. For the in vitro determination of 10B uptake, the cells were incubated in medium containing BSH and exposed to electric pulses. Boron levels were determined by inductively coupled plasma atomic emission spectrometry. In vivo, tumours were exposed to electric pulses 3 min after intravenous BSH injection. At different times after exposure the 10B concentration was determined in tumours and in blood. A difference in the 10B accumulation in the two cell lines was observed after continuous incubation of cells with BSH. No accumulation of 10B was observed in MCF7 cells, whereas in B16F1 cells, 10B accumulated well and reached a plateau within 30 min. Electroporation of these cells resulted in an accumulation of 10B into MCF7 cells up to the level of 10B in B16F1 cells. In vivo, the application of electric pulses increased and prolonged the entrapment of 10B (BSH) in the B16F1 melanoma tumours. A sufficient concentration of 10B was present in the tumour exposed to electric pulses for up to 24 h. Boron was quickly washed out from the blood and the level was below the concentrations in the tumours exposed to electric pulses at 2 h. The results of this study show that electroporation may provide a tool to increase boron concentration in the cells that have impaired transport of BSH through the plasma membrane. Furthermore, prolonged entrapment of BSH in tumours in vivo may, in addition to electroporation, be caused by the modifying effect of electric pulses on blood flow.     

In vivo imaging of the neutron capture therapy agent BSH in mice using (10)B MRI.

Boron neutron capture therapy (BNCT) is an experimental cancer treatment modality requiring the targeting of (10)B-enriched compounds to the tumor, which is then irradiated by low-energy neutrons. One of the boron-containing compounds used for this purpose is the mercaptoborane Na(2)B(12)H(11)SH (BSH). The first in vivo MR images of (10)B-enriched BSH are presented here. BSH, injected into the tail vein of mice with implanted M2R melanoma xenografts, was imaged using 3D gradient echo (10)B MRI. (10)B NMR spectroscopy, localized mainly to the tumor by virtue of the use of a small surface coil, was applied to measure the T(1) (2.9 +/- 0.3 ms) and T(2) (1.75 +/- 0.25 ms) values of the (10)B signal. The MRI experiments detected levels of about 20 ppm (microg boron / g tissue) at 6 x 6 x 6 mm spatial resolution in a total scan time of 16 min. Magn Reson Med 46:13-17, 2001.     

Boron biodistribution in beagles after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose complex.

Boron biodistribution after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose (BPA-F) complex was investigated in six dogs. Blood samples were evaluated during and following doses of 205 and 250 mg/kgbw BPA in a 30 min infusion, and 500 mg/kgbw in a 1h infusion. Samples from whole blood, urine, brain and other organs were analysed for boron content after varying times following the onset of infusion. The whole blood boron concentrations declined from 27 to 8.4 ppm over the period of 39-165 min after the onset of infusion and the levels increased from 1.9 to 12 ppm in the grey matter of the brain over the same period. The boron concentrations in whole blood decreased steadily, whereas the boron values in brain tissue rose steadily with time. It was concluded that whole blood boron concentrations do not seem to reflect accurately the boron concentration in brain tissue at respective time points.     

Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: Combined administration of BSH and BPA

Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70–85 ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy.     

Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood–brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.     

Assessment of perfusion, function, and myocardial metabolism after infarction with a combination of low-dose dobutamine tetrofosmin gated SPECT perfusion scintigraphy and BMIPP SPECT imaging

BACKGROUND: Tetrofosmin gated single photon emission computed tomography (SPECT) allows simultaneous assessment of regional myocardial perfusion, global and regional left ventricular function, and function at rest and during pharmacologic intervention. SPECT with fatty acid analogues, such as beta-methyl-iodophenyl-pentadecanoic acid (BMIPP), can be used to monitor metabolic changes induced by myocardial ischemia. In this work, the results of both studies obtained in patients with recent myocardial infarction are integrated. METHODS: Twenty patients underwent tetrofosmin and BMIPP scintigraphy with a 3-head camera. Two consecutive tetrofosmin gated SPECT acquisitions were performed 60 minutes after administration of technetium-99m tetrofosmin (925 MBq) at rest (3x20 stops of 9 s; matrix 64x64 over 360 degrees . One acquisition was made at rest, and the second was made during dobutamine infusion (10 microg/kg/min). Regional functional abnormalities were quantified and expressed as wall thickening severity (WTsev) in arbitrary units. Left ventricular ejection fraction and volumes were assessed with the Cedars Sinai algorithm. BMIPP imaging started 20 minutes after iodine 123-BMIPP (150 MBq) administration at rest (3x32 stops of 60 s; matrix 64x64 over 360 degrees; medium energy collimators). Tracer uptake was scored according to a 25-segment model. RESULTS: Sixteen of 18 patients had regional functional abnormalities at baseline (average WTsev 13.7 units). The WTsev score at baseline correlated well with the degree of residual perfusion. During dobutamine infusion, WTsev did not change (from 23.4 to 23.6 units) in 5 patients; it decreased (from 16.1 to 5.9 units) in 11 patients; and it increased (from 13.0 to 22.3 units) in 3 patients. An increase or decrease in WTsev during dobutamine infusion was associated with the presence of a considerable amount of BMIPP mismatched myocardium, whereas no change in WTsev was preferentially associated with a BMIPP matched pattern and perfusion defects with a higher severity score. CONCLUSION: Immediately after infarction, the severity of regional dysfunction at rest correlated well with the perfusion defect severity. Improvement in regional function during dobutamine administration is associated with less severe perfusion defects and a considerable amount of BMIPP mismatched myocardium, both suggesting viability.     

Intravenous cholangiography in different degrees of common bile duct obstruction. An experimental study in the dog.

A total of 83 cholangiograms was performed in three cholecystectomized dogs equipped with Thomas cannulas through which complete and different degrees of incomplete common bile duct obstruction were produced. With incomplete common bile duct obstruction, the iodine concentration in the bile necessary for radiographic visualization of the common duct was always obtained for all three tested iodipamide dosages of .3, .6, and 1.2 ml/kg, infused over 30 minutes. The largest dose resulted in the highest biliary iodine concentrations. With increasing obstruction, an increasing delay of the biliary iodipamide excretion was noted. With complete common bile duct obstruction the iodine concentration in the bile necessary for radiographic visualization of the common duct was never obtained, even with an iodipamide dose increased to 1.8 ml/kg and/or prolongation of the contrast material infusion time from 30 minutes to 2 and 6 hours. Nevertheless, the highest biliary iodine concentration in complete common bile duct obstruction resulted with the largest iodipamide dose (1.8 ml/kg) and the shortest infusion time (30 minutes).     

Hepatobiliary toxicity of 5-fluoro-2'-deoxyuridine. Intra-arterial versus portal venous routes of infusion.

Biliary sclerosis remains the dose-limiting toxicity in a subset of patients receiving hepatic arterial (HA) floxuridine (FUDR) for the treatment of hepatic malignancy. To investigate the etiology of FUDR-associated sclerosing cholangitis, portal vein catheters were placed in mixed-breed hounds (N = 4) and connected to an implanted infusion pump system. Floxuridine 0.3 mg/kg/day was infused for 49 to 77 days each, as a continuous infusion. Cholangiograms were performed before and after infusion, and weekly liver function tests were obtained. The results were compared to dogs (N = 6) that received HA FUDR 0.3 mg/kg/d x 30 days, and dogs (N = 5) that received HA saline for 100 days. Elevation in the serum glutamic pyruvic transaminase and alkaline phosphatase, indistinguishable from the HA group, was seen in all four dogs with portal vein infusion. Maximum bilirubin levels ranged from 0.6 to 3.0 (mean 1.7), compared to a range of 6.4 to 28 (mean 13.4) for the HA dogs. Cholangiograms demonstrated hepatic volume loss consistent with hepatocellular injury, but no biliary sclerosis. These data suggest that sclerosing cholangitis resulting from intra-arterial infusion of FUDR is unlikely to be due to metabolites of the drug excreted in the bile, but due to direct toxicity to the biliary tree.     

Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits

PURPOSE: To evaluate gadoterate meglumine as a contrast agent for interstitial magnetic resonance (MR) lymphography in combination with an adapted fast three-dimensional (3D) MR sequence. MATERIALS AND METHODS: In 12 New Zealand White rabbits, 0.5 mL of undiluted gadoterate meglumine was injected subcutaneously into the dorsal foot pad (n = 9) or the foreleg (n = 3) bilaterally. Immediately after administration, a slight massage was performed at the injection site. Imaging was performed with a 3D spoiled gradient-recalled echo sequence (6.7/1.6 [repetition time msec/echo time msec]; field of view, 28.0 x 19.6; two signals acquired) similar to that used for 3D MR angiography. Thus, 3D maximum intensity projection images could be obtained. Images were obtained before injection and 5, 15, 30, 60, and 120 minutes after injection. RESULTS: In the hind legs, as many as four successive lymph node groups were depicted with maximum enhancement after 5-15 minutes for the popliteal lymph node group, 15-30 minutes for the inguinal lymph group, and 30-60 minutes for the iliac-paraaortal lymph node group; the iliac-paraaortal lymph node group was not consistently enhanced. In the forelegs, four successive lymph node groups, including axillary and mediastinal lymph node groups, showed marked gadolinium uptake, with maximum enhancement 5-15 minutes after injection. CONCLUSION: As a widely tested positive-enhancing T1 contrast agent with favorable safety features, gadoterate meglumine allows the depiction of three to four successive lymph node groups early after subcutaneous injection. With the sequence used, 3D MR lymphangiograms can be obtained.     

Porphyrin-mediated boron neutron capture therapy: evaluation of the reactions of skin and central nervous system

PURPOSE: Recently, various boronated porphyrins have been shown to preferentially target a variety of tumour types. Of the different porphyrins evaluated, copper tetra-phenyl-carboranyl porphyrin (CuTCPH) is a strong candidate for future preclinical evaluation. In the present study, the responses of two critical normal tissues, skin and central nervous system (CNS), to boron neutron capture (BNC) irradiation in the presence of this porphyrin were evaluated. MATERIALS AND METHODS: Standard models for the skin and spinal cord of adult male Fischer 344 rats were used. CuTCPH was administered by intravenous infusion at a dose of 200 mg x kg(-1) body weight, over 48 h. The thermal beam at the Brookhaven Medical Research Reactor was used for the BNC irradiations. The 20-mm diameter irradiation field, for both the skin and the spinal cord, was located on the mid-dorsal line of the neck. Dose-response data were fitted using probit analysis and the doses required to produce a 50% incidence rate of early and late skin changes or myeloparesis (ED(50) +/- SE) were calculated from these curves. RESULTS: Biodistribution studies indicated very low levels of boron (<3 microg x g(-1)) in the blood 3 days after the administration of CuTCPH. This was the time point selected for radiation exposure in the radiobiological studies. Levels of boron in the CNS were also low (2.8 +/- 0.6 microg x g(-1)) after 3 days. However, the concentration of boron in the skin was considerably higher at 22.7 +/- 2.6 microg x g(-1). Single radiation exposures were carried out using a thermal neutron beam. The impact of CuTCPH-mediated BNC irradiation on the normal skin and CNS at therapeutically effective exposure times was minimal. This was primarily due to the very low blood boron levels (from CuTCPH) at the time of irradiation. Analysis of the relevant dose-effect data gave compound biological effectiveness factors of about 1.8 for skin (moist desquamation) and about 4.4 for spinal cord (myeloparesis) for CuTCPH. These values were based on the BNC radiation doses to tissues calculated using the blood boron levels at the time of irradiation. CONCLUSIONS: CuTCPH-mediated BNC irradiation will not cause significant damage to skin and CNS at clinically relevant radiation doses provided that blood boron levels are low at the time of radiation exposure.     

Three-dimensional gadolinium-enhanced MR imaging of the breast: pulse sequence with fat suppression and magnetization transfer contrast. Work in progress

A pulse sequence with magnetization transfer contrast and fat suppression was used in three-dimensional magnetic resonance imaging of the breast. Two healthy volunteers, one person with silicone implants, and 12 patients with clinical and/or mammographic findings suspicious for malignancy were evaluated prior to and following infusion of gadopentetate dimeglumine. Imaging time was approximately 7 minutes for each set of data (128 sections). Final voxel dimensions ranged from 1.4 x 0.8 x 0.8 mm to 1.6 x 0.9 x 0.9 mm. All carcinomas, including ductal and lobular types, were enhanced before and after infusion of contrast medium. Multifocal carcinoma and inflammatory carcinoma could be clearly visualized. Enhancement was not evident in patients with fat necrosis (n = 1) or scar (n = 1). Fibrocystic changes in one patient were visible as areas of increased signal intensity on preinfusion images. Resolution and contrast of MR images obtained with this pulse sequence appeared to be improved over that achieved with conventional breast MR imaging techniques. This method has the potential to supplement conventional diagnostic methods in the evaluation of breast disease.     

The effect of moderate aerobic exercise and relaxation on secretory immunoglobulin A

A deficiency in secretory immunoglobulin A (sIgA) is associated with recurrent upper respiratory tract infections both in the general community and in elite athletes. The aim of this paper was to investigate the effect of aerobic exercise and relaxation on various indices of sIgA in 12 male and 8 female adults who varied in levels of recreational activity. Salivary samples were obtained before, immediately after and 30 minutes after an incremental cycle ergometer test to fatigue, after 30 minutes of cycling at 30% or 60% of maximum heart rate, and after 30 minutes of relaxation with guided imagery. Each session was run on a separate day. When expressed in relation to changes in salivary flow rate, sIgA did not change after exercise. However, both the absolute concentration and secretion rate of sIgA increased during relaxation (167 +/- 179 microg x ml(-1), p < 0.001; and 37 +/- 71 microg x min(-1), p < 0.05 respectively). Nonspecific protein increased more than sIgA during incremental exercise to fatigue (decrease in the sIgA/protein ratio 92 +/- 181 microg x mg protein(-1), p < 0.05), but sIgA relative to protein did not change during relaxation. Our findings suggest that sIgA secretion rate is a more appropriate measure of sIgA than sIgA relative to protein, both for exercise and relaxation. These data suggest the possibility of using relaxation to counteract the negative effects of intense exercise on sIgA levels.     

Magnetic resonance angiography with gadolinium (Gd-DTPA) versus baseline magnetic resonance angiography in the study of the intracranial circulation]

The authors evaluated the role of GdDTPA in magnetic resonance angiography (MRA) of intracranial vessels. Fifteen patients affected with different conditions underwent MRA of intracranial vessels before and after paramagnetic contrast medium infusion. A superconductive 1.5-T magnet (Magnetom Siemens) was used, and a head circular coil, together with the 3DFT TOF technique. The enhanced exam was performed following the infusion of 0.2 ml/kg of GdDTPA in about 2 minutes, with simultaneous MRA image acquisition. To compare enhanced with unenhanced images relative to signal intensity, the signal increase at the basilar artery and carotid sinus was studied, together with signal-to-noise (S/N) ratio and spatial resolution. During acquisition, enhanced MRA images at the basilar artery showed a mean intensity value of 423.8 +/- 33.2 vs 357.8 +/- 53.2 of unenhanced scans; a statistically significant difference (p < 0.05; p < 0.01) was observed in favor of enhanced images. At the carotid sinus, enhanced MRA showed 184.5 +/- 28.4 mean intensity value vs 190.5 +/- 19.8 of unenhanced exams; no statistically significant difference was observed (p < 0.05; p < 0.01) in favor of unenhanced exams. At the basilar artery the S/N ratio of baseline exams was 1.9 vs 2.2 for enhanced scans; at the carotid sinus S/N ratio was 2.4 (unenhanced) vs 2.3 (enhanced). Thus, MRA allowed better visualization of peripheral branches of arterial (95.6%) and venous vessels, which unenhanced scans always failed to depict; on the other hand, enhanced images exhibited poorer definition of arterial vessels which were never isolated from the background. The simultaneous visualization of arterial and venous vessels, of choroid plexus and mucosae, affect the quality of enhanced angiograms. At present, GdDTPA is the sole contrast medium suitable for MRA intracranial vessels even though, due to its pharmacokinetic features, it is not the optimum medium.     

Hepatic MR imaging with ferumoxides: multicenter study of safety and effectiveness of direct injection protocol

PURPOSE: To compare the safety and effectiveness of an undiluted direct injection of ferumoxides with those of a diluted slow infusion of ferumoxides during 30 minutes in patients with known liver lesions or in those suspected of having them. MATERIALS AND METHODS: Two hundred thirty-three patients at 16 institutions were randomized to receive either an undiluted direct injection of 0.56 mg of iron per kilogram of body weight of ferumoxides administered during 2 minutes (2 mL/min) or a diluted slow infusion administered during 30 minutes. Safety was assessed with monitoring for adverse events and laboratory tests. For sensitivity, specificity, and accuracy analysis, two independent blinded observers identified and classified lesions as benign or malignant with precontrast images and with pre- and postcontrast images combined. RESULTS: There was no statistically significant difference in adverse events in the group with direct injection compared with those in the group with infusion (21 [18%] of 114 patients vs 19 [17%] of 112 patients, respectively). No serious adverse events were observed. The most common adverse events in the group with direct injection versus the group with infusion were headache (five [4%] of 114 vs three [3%] of 112, respectively) and back pain (five [4%] of 114 vs three [3%] of 112, respectively). Overall, in 68 (62%) of 109 patients with direct injection and 71 (66%) of 108 patients with infusion, additional magnetic resonance (MR) imaging information was obtained after ferumoxides administration (P =.67). Sensitivity, specificity, and accuracy for the diagnosis of malignancy were significantly improved by adding images obtained after ferumoxides administration to the images obtained before contrast agent administration (P <.05 for all comparisons). CONCLUSION: Direct injection of ferumoxides has safety and effectiveness profiles similar to those of slow infusion of the agent. Further findings indicate that the addition of ferumoxides increases the sensitivity and specificity of hepatic MR evaluation when compared with unenhanced MR imaging.     

New generation of monomer-stabilized very small superparamagnetic iron oxide particles (VSOP) as contrast medium for MR angiography: preclinical results in rats and rabbits

The purpose of this study was to evaluate the signal enhancement characteristics of very small superparamagnetic iron oxide particles (VSOP)-C63, a new monomer-coated, iron oxide-based magnetic resonance (MR) blood pool contrast medium with a very small particle size and optimized physical properties. Equilibrium MR angiography (MRA) of rats (thoracic and abdominal vessels) was performed at 1.5 T with a three-dimensional gradient-recalled echo (3D GRE) technique (TR/TE 6.6/2.3 msec, flip angle 25 degrees ) before and after (every 3-5 minutes up to 50 minutes) i.v. injection of VSOP-C63 [dosages: 15, 30, 45, 60, 75, and 90 micromol Fe/kg; diameter: 8 nm; relaxivities at 0.47 T: R1 = 30 l/(mmol * s); R2 = 39 l/(mmol * s)]. First-pass MRA images (3D-GRE, TR/TE 4.5/1.7 msec, flip angle 25 degrees ) were obtained with 45 micromol Fe/kg VSOP-C63 in comparison with 0.2 mmol Gd/kg of gadolinium diethylene triamine pentaacetic acid (Gd DTPA; before and every 5 seconds p.i.). MRA (3D GRE, TR/TE 4.5/1.7 msec, flip angle 25 degrees) of coronary vessels in rabbits was performed after i.v. injection of 45 micromol Fe/kg of VSOP-C63. In rats maximal S/N ratio in thoracic and abdominal arteries directly after i.v. injection of VSOP-C63 was 25 +/- 1, 43 +/- 2, 49 +/- 4, 57 +/- 3, 64 +/- 3, and 63 +/- 3 for the different dosages. Blood half-life was dose dependent (15 +/- 2, 20 +/- 3, 29 +/- 6, 37 +/- 5, 61 +/- 16, and 86 +/- 21 minutes). At a dose of 30 micromol Fe/kg even small intrarenal arteries were sharply delineated. First-pass MRA showed no significant difference in the S/N ratio between Gd-DTPA (71.5 +/- 11.5) and VSOP-C63 (65.1 +/- 18. 3). The proximal segments of the coronary arteries in rabbits were clearly depicted at a dose of 45 micromol Fe/kg. The monomer-coated, iron oxide-based contrast medium VSOP-C63 exhibits favorable properties as a blood pool agent for both equilibrium and first-pass MRA. J. Magn. Reson. Imaging 2000;12:905-911.     

Normal values for sincalide cholescintigraphy: comparison of two methods.

PURPOSE: To establish normal gallbladder ejection fraction (GBEF) values for two sincalide (cholecystokinin [CCK]) infusion dose rates, 0.01 microg per kilogram of body weight infused for 3 minutes and 0.01 microg/kg infused for 60 minutes. MATERIALS AND METHODS: Twenty healthy subjects were examined. GBEFs were calculated for the 3-minute infusion and for each 15-minute interval for the 60-minute infusion. Normal values were determined by using the mean +/- 2 SDs and a more rigorous statistical analysis. RESULTS: With the 3-minute infusion, GBEFs were significantly more variable than with the 45- and 60-minute values for the 60-minute infusion (P < .01, .002). With intervals including 95% of the population, the GBEF lower normal range was 16.8% for the 3-minute infusion but 31% and 41% for the 45- and 60-minute values, respectively. GBEFs of less than 35% were noted in six (30%) of 20 healthy subjects with the 3-minute infusion but in only one with the 60-minute infusion. Hepatobiliary ultrasonography was performed in six of seven subjects with GBEF of 36% or less, and US findings in all six were normal. CONCLUSION: A 3-minute infusion of sincalide, 0.01 microg/kg, produces too variable a GBEF response to establish a clinically useful normal range. With 0.01 microg/kg infused for 60 minutes, clinically useful normal values were established at 45 and 60 minutes.     

Current clinical results of the Tsukuba BNCT trial.

Nine high grade gliomas (5 glioblastomas and 4 anaplastic astrocytomas) were treated with BSH-based intaoperative boron neutron capture therapy (IOBNCT). BSH (100 mg/kg body weight) was intravenously injected, followed by single fraction irradiation using the mixed thermal/epithermal beam of Japan Research Reactor 4. The blood boron level at the time of irradiation averaged 29.9 (18.8-39.5)microg/g. The peak thermal neutron flux as determined by post-irradiation measurements varied from 1.99 to 2.77x10(9) n cm(-2)s(-1). No serious BSH-related toxicity was observed in this series. The interim survival data in this study showed median survival times of 23.2 months for glioblastoma and 25.9 months for anaplastic astrocytoma, results which are consistent with the current conventional radiotherapy with/without boost radiation. Of the 4 residual tumors, 2 showed complete response (CR) and 2 showed partial response (PR) within 6 months following BNCT. No linear correlation was proved between the dose and the occurrence of early neurological events. The maximum boron dose of 11.7-12.2 Gy in the brain related to the occurrence of radiation necrosis. The clinical application of a mixed thermal/epithermal beam and JRR-4 facilities on BSH-based IOBNCT proved to be safe and effective in this series.     

The usefulness of 18F-FDG PET images obtained 2 hours after intravenous injection in liver tumor

Liver tumors, especially hepatocellular carcinomas (HCCs), often exhibit no contrast with surrounding non-tumorous liver tissue in F-18-fluoro-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) images obtained at the usual interval of one hour after intravenous FDG injection. We evaluated the usefulness of FDG PET studies of liver tumors performed 2 hours after intravenous injection. METHODS AND MATERIALS: Fifteen pretherapeutic patients with 33 liver tumors were studied, including 11 patients with 18 HCCs, and 4 patients with 15 metastatic liver tumors (METAs) from 3 colorectal carcinomas and 1 esophageal carcinoma. After transmission scans, emission scans were obtained 45-55 minutes and 115-125 minutes after intravenous injection of 185-370 MBq FDG as early images and delayed FDG PET images, respectively. Visual analysis of early and delayed images was performed, and the FDG uptake in the tumor to that in nontumorous liver ratio (T/N ratio), the FDG uptake in tumor to that in soft-tissue ratio (T/S ratio) and the FDG uptake in non-tumorous liver to that in soft-tissue ratio (N/S ratio) were calculated for each image. RESULTS: In visual analysis, visual improvement seen in images was observed in 6 of 18 HCC lesions and all 15 META lesions. In quantitative analysis, the mean T/S ratio and T/N ratio of HCCs in early images were 4.97 and 1.90, respectively, and those in delayed images were 6.24 and 2.20, respectively. The mean T/S ratio and T/N ratio of METAs in early images were 5.97 and 2.21, respectively, and those in delayed images were 6.99 and 3.80, respectively. The T/S ratio of HCCs and T/S ratio and T/N ratio of METAs were significantly higher in delayed images than in early images. The mean N/S ratios of HCC cases were 2.58 in the early images and 2.57 in the delayed images, but the ratio showed no constant tendency in the images. All N/S ratios of META cases were decreased in delayed images, although the significance of the difference between early and delayed images in N/S ratios was not analyzed because of the small number of cases. CONCLUSION: FDG PET studies performed 2 hours after intravenous injection were useful for clear visualization of liver tumors, especially metastatic liver tumors.