Comparison of iodine-123-disintegrins for imaging thrombi and emboli in a canine model

Disintegrins are peptides found in viper venoms which bind to platelets through the glycoprotein IIb-IIIa receptor. The purpose of this work was to evaluate the ability of disintegrins to image thrombi and emboli in vivo. METHODS: Eight disintegrins (bitistatin, albolabrin, echistatin, eristostatin, kistrin, mambin, halysin and barbourin) were purified from snake venom. After radiolabeling with 123I, disintegrins were tested for their ability to image 24-hr-old experimental deep vein thrombi (DVT) and pulmonary emboli in a canine model. Labeled fibrinogen and platelets were used as controls. Gamma camera imaging was performed during the first 4 hr, after which tissue samples were collected for counting. RESULTS: Of the disintegrins tested, 123I-bitistatin had higher uptake in DVT (0.21 +/- .06% ID/g) than any other disintegrin (0.009-0.036%/g, p < 0.05). Bitistatin had higher DVT-to-blood ratios (9.8 +/- 2.5) than all other disintegrins, 125I-fibrinogen or 99mTc-HMPAO-platelets (p < 0.05). Images of DVT obtained with 123I-bitistatin were focally positive within 1 hr and improved by 4 hr. In pulmonary emboli, the absolute uptake of 123I-bitistatin (0.64 +/- 0.17% ID/g) was higher than all other compounds (p < 0.05), although barbourin had moderate uptake (0.23 +/- 0.11% ID/g) and may also be useful for imaging pulmonary embolism (PE). The uptake of bitistatin in PE was superior to both 125I-fibrinogen (0.18 +/- 0.02% ID/g) (p < 0.05) and 99mTc-HMPAO-platelets (0.14 +/- 0.02% ID/g, p < 0.05). Iodine-123-bitistatin had embolus-to-blood ratios averaging 27 +/- 7, which was higher than platelets, fibrinogen, echistatin, mambin or halysin (p < 0.05). Iodine-123-bitistatin background in lungs, liver and heart were low, which permitted visualization of all pulmonary emboli by 2-4 hr after injection. CONCLUSION: Labeled bitistatin should be investigated further as an agent which may permit rapid imaging of both thrombi and emboli.     

Bispecific monoclonal antibody-mediated targeting of an indium-111-labeled DTPA dimer to primary colorectal tumors: pharmacokinetics, biodistribution, scintigraphy and immune response

Eleven patients with primary colorectal carcinoma tumors (4 +/- 2 cm) were given intravenous injections of 1-10 mg of an anti-CEA, anti-In-DTPA bispecific Fab'-Fab monoclonal antibody, and 2-8 days later, were injected with 1.2-4.2 nmol of an 111In-labeled DTPA dimer (6 mCi). The bispecific antibody exhibited good stability and F(ab)'2-like pharmacokinetics. After injection, the 111In-DTPA dimer distributed in a large volume (88 ml/kg-180 ml/kg) and cleared through the kidneys (mean residence time in the whole body: 9 hr-16 hr). Uptake of 111In by the tumor using this two-step technique (1.8%-17.5% injected dose ID/kg, measured from surgical samples 48 hr after hapten injection) was not found significantly lower than that achieved with our reference 111In-labeled anti-CEA F(ab)'2 1 to 4 days after injection in six patients with similar clinical status (5.5%-30.2% ID/kg). In addition, tumor-to-blood and tumor-to-liver uptake ratios were significantly improved (blood 7.8 versus 4.2, liver 2.8 versus 0.8). As a result, low background images allowed detection of 12 of 13 lesions, 4 hr and 24 hr after hapten injection. However, 7 of 11 patients developed HAMA.     

Sensitivity reaction to parenteral vitamin B12: recurrence of symptoms after Marmite ingestion

No other successful nuclear method, besides bone scanning, has been reported in the literature for in vivo imaging of olfactory neuroblastoma. In this article, excellent uptake is reported by an In-111 labeled bleomycin complex (BLMC) in the ethmoid region of a histologically confirmed olfactory neuroblastoma. The uptake of BLMC was 0.7 x 10(-3)% ID/g at 48 hours after injection, and tumor-to-muscle and tumor-to-fat ratios were 6:1 and 11:1, respectively. The authors conclude that BLMC should be considered as a useful imaging agent, and the BLMC has potential as a radiochemotherapeutic agent against an olfactory neuroblastoma.     

Imaging experimental osteomyelitis using radiolabeled liposomes

We evaluated radiolabeled liposomes (liposomes labeled both with 99mTc and 111In) for the early detection of osteomyelitis in an experimental model. METHODS: Liposomes, containing 5% polyethylene glycol-distearoyl phosphatidylethanolamine with encapsulated glutathione and deferoxamine, were prepared and labeled with 99mTc and 111In by a previously described method. Acute osteomyelitis was induced in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and Staphylococcus aureus in the tibial bone marrow. Serial imaging studies, consisting of radiolabeled liposome imaging (2-4 mCi 99mTc and 75-125 microCi 111In), 99mTc-methylene diphosphonate (MDP) (3-5 mCi) and 67Ga-citrate (500 microCi), were performed starting at the third day after injection. Each radionuclide study was separated by at least 2 days. The animals also underwent radiography of the lower extremities. The animals were then killed and the infected tibia was excised for histopathology. RESULTS: For interpreting relative efficacy of individual radiopharmaceuticals, only animals showing positive histopathological findings (n = 9) were considered. Radiographs (Days 12, 13) were conclusive for osteomyelitis in only 3 rabbits. Radiolabeled liposome imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Though the lesion could be delineated as early as 8 hr postinjection in the 99MTc window, the best target-to-nontarget ratio (T/NT) of 1.86 +/- 0.19 was obtained at 48 hr in the 111In window. Three-phase 99mTc-MDP scan (Day 7) was positive in only 5 rabbits with 3 hr T/NT of 1.6 +/- 0.23. Galium-67-citrate images (Days 9-11) were positive in 8 cases and equivocal in 1, the mean 48 hr T/NT being 1.74 +/- 0.24. These results show liposomes are better than 99mTc-MDP for imaging bone infection. Given the early localization and better quality of the images, radiolabeled liposomes also exhibited advantages over 67Ga-citrate for detection of acute osteomyelitis.     

Indium-111-DOTA-lanreotide: biodistribution, safety and radiation absorbed dose in tumor patients

Imaging with radiolabeled somatostatin/vasoactive intestinal peptide analogs has recently been established for the localization diagnosis of a variety of human tumors including neuroendocrine tumors, intestinal adenocarcinomas and lymphomas. This study reports on the biodistribution, safety and radiation absorbed dose of 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N'-tetraacetic acid (DOTA)-lanreotide, a novel peptide tracer, which identifies hSST receptor (R) subtypes 2 through 5 with high affinity, and hSSTR1 with low affinity. METHODS: The tumor localizing capacity of 111In-DOTA-lanreotide was initially investigated in 10 patients (3 lymphomas, 5 carcinoids and 2 intestinal adenocarcinomas). Indium-111 -DOTA-lanreotide was then administered to 14 cancer patients evaluated for possible radiotherapy with 90Y-DOTA-lanreotide (8 neuroendocrine tumors, 4 intestinal adenocarcinomas, 1 Hodgkin lymphoma and 1 prostate cancer). After intravenous administration of 111In-DOTA-lanreotide (approximately = 150 MBq; 10 nmol/patient), sequential images over one-known tumor site were recorded during the initial 30 min after peptide application. Thereafter, whole-body images were acquired in anterior and posterior views up to 72 hr postinjection. Dosimetry calculations were performed on the basis of scintigraphic data, urine, feces and blood activities. A comparison with 111In-DTPA-D-Phe1-octreotide (111In-OCT) scintigraphy was performed in 8 of the patients. RESULTS: After an initial rapid blood clearance [results of biexponential fits: T(eff1) 0.4 min (fraction a1 80%) and T(eff2) 13 min (fraction a2 14%)], the radioactivity was excreted into the urine and amounted to 42% +/- 3% of the injected dose (%ID) within 24 hr and 62% +/- 6%ID within 72 hr after injection of 111In-DOTA-lanreotide. In all patients, tumor sites were visualized during the initial minutes after injection of 111In-DOTA-lanreotide. The mean radiation absorbed dose amounted to 1.2 (range 0.21-5.8) mGy/MBq for primary tumors and/or metastases. The effective half-lives of 111In-DOTA-lanreotide in the tumors were T(eff1) 4.9 +/- 2.2 and T(eff2) 37.6 +/- 6.6 hr, and the mean residence time tau was 1.8 hr. The highest radiation absorbed doses were calculated for the spleen (0.39 +/- 0.13 mGy/MBq), kidneys (0.34 +/- 0.08 mGy/MBq), urinary bladder (0.21 +/- 0.03 mGy/MBq) and liver (0.16 +/- 0.04 mGy/MBq). The effective dose was 0.11 +/- 0.01 (range 0.09-0.12) mSv/MBq. During the observation period of 72 hr, no side effects were noted after 111In-DOTA-lanreotide application. The 111In-DOTA-lanreotide radiation absorbed tumor dose was significantly higher (ratio 2.25 +/- 0.60, p < 0.01) when directly compared with 111In-OCT. CONCLUSION: Indium-111 -DOTA-lanreotide shows a high tumor uptake for a variety of different human tumor types, has a favorable dosimetry over 111In-OCT and is clinically safe.     

Influenza A virus interaction with murine lymphocytes. II. Changes in lymphocyte surface properties induced by influenza virus A/Japan 305 (H2N2)

This report describes changes in surface properties of rat thoracic duct lymphocytes (TDL) induced by influenza virus A/Japan 305 (H2N2). After incubation with virus at 37 degrees C, sialic acids were released from the membranes of TDL WITH CONCOMItant reduction in their mean electrophoretic mobility. Autoradiographs of TDL which had been incubated with 125I virus at 4 degrees C showed that the particles attached to nearly all the lymphocytes although there was variation in the amount of virus bound per cell. Attachment occurred rapidly with maximum labeling evident after incubation at 4 degrees C for 5 min. Incubation at 37 degrees C for 1 hr resulted in a 10 to 18% reduction in the incidence of labeled TDL suggesting that some virus eluted spontaneously. When 125I-virus-treated TDL were incubated in syngeneic serum, substantial amounts of virus eluted reducing the incidence of labeled cells by 50%. In addition, evidence was obtained by indirect immunofluorescence that syngeneic serum contains antibodies which react with sites on the lymphocyte surface exposed by the viral neuraminidase.     

Macromolecular intravenous contrast agent for MR lymphography: characterization and efficacy studies

PURPOSE: To determine the pharmacokinetic and magnetic resonance (MR) imaging properties of diethylenetriaminepentaacetic acid (DTPA) conjugated with a polyglucose-associated macrocomplex (PGM), which accumulates in lymph nodes. MATERIALS AND METHODS: In 124 normal and 20 tumor-bearing rats, Gd-DTPA PGM was administered intravenously in doses of 2, 10, 20 mumol gadolinium per kilogram of tissue. RESULTS: Mean blood half-life was 2 hours. Maximum accumulation in peripheral (33.0% injected dose [ID]/g +/- 16.2 [standard deviation]) and central lymph nodes (63.2% ID/g +/- 16.5) was observed within 24 hours after administration. The optimum dose range was 10-20 mumol Gd/kg in rats. At 24 hours after administration of 20 mumol Gd/kg, the signal-to-noise ratio increased from 30.9 +/- 0.4 to 83.2 +/- 5.2 in normal lymph nodes (P < .001). Differentiation between normal and metastatic lymph nodes was improved. CONCLUSION: When labeled with Gd-DTPA, the PGM-based graft copolymer significantly increases signal intensity at MR imaging of normal but not metastatic lymph nodes without causing distortion artifacts.     

Oxygen consumption, lactate metabolism, and gastric intramucosal pH in an experimental liver transplantation model

We have evaluated whether myocardial uptake of the fatty acid analog 123I-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) is dependent on the dietary state. METHODS: We compared the biodistribution of 150 MBq of 123I-BMIPP in six healthy volunteers in two states: after at least 12 hr of fasting and after oral glucose loading (75 g) 60 min before tracer administration, followed by a meal enriched in carbohydrates and protein. Planar and tomographic acquisitions were performed over a 4-hr time period after tracer injection; data were corrected for radioactive decay and injected dose. Radioactivity was measured in blood samples drawn at several points. RESULTS: Significant increases of glycemia and insulinemia and a significant drop in plasma nonesterified acids were documented after glucose loading. Half-time values for plasma radioactivity were significantly shorter in the glucose-loaded state than in the fasted state (4.3 +/- 1.4 min compared to 6.3 +/- 1.3 min, p < 0.05). Activity in the heart and liver tended to be higher in the glucose-loaded state than in the fasted state. SPECT images at 0.5 hr after tracer injection demonstrated that the myocardial wall-to-cavity ratio was higher after glucose than in the fasted state (2.53 +/- 0.59 compared to 2.11 +/- 0.21, p = 0.15). Washout from the liver between 1 and 4 hr after injection increased from 18.6% +/- 4.4% in the fasted study to 24.1% +/- 2.4% after glucose (p = 0.04). Washout from the myocardium between 0.5 and 3.5 hr after injection increased from 13.1% +/- 8.8% in the fasted study to 24.0% +/- 3.7% after glucose (p = 0.05). CONCLUSION: These results indicate that fasting before BMIPP scintigraphy is not mandatory to obtain adequate SPECT images. At the tire when SPECT is usually performed, glucose loading may provide improved ratios between myocardial and blood pool activity.     

Aspects of 1,25-dihydroxyvitamin D3 binding sites in fish: an autoradiographic study

The distribution of specific binding sites for vitamin D3 in adult female and male Xiphophorus helleri is studies after injection of tritiated 1,25-dihydroxyvitamin D3 (vitamin D) by thaw-mount autoradiography. Five hours after injection of labeled vitamin D specific nuclear binding is present in brain, pituitary, skin, gills, cartilage, gut, liver, pancreas, spleen, kidney, muscle, ovary, and testis. Cytoplasmic binding exists strongest in gills, gut, and kidney while it is comparatively weak in hepatocytes. In reproductive organs cytoplasmic retention of radioactivity is also present in oocytes. Weak nuclear labeling exists in interstitial cells in ovary. Conspicuous nuclear labeling exists in active lobules of testis, while inactive lobules show occasionally a few labeled cells. The results demonstrate specific binding and retention of vitamin D in many target organs of teleost fish, suggesting an extensive and multifunctional regulatory role of this steroid hormone of sunlight.     

Intra-individual comparison of 3(R)-BMIPP and 3(S)-BMIPP isomers in humans

The racemic 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) is currently used at several centers for myocardial metabolic imaging with SPECT. Recently, the 3(R)-BMIPP isomer showed a 20%-25% higher myocardial uptake and lower liver uptake than 3(S)-BMIPP in fasted rats. The aim of this study was to determine if these differences in myocardial and liver uptake also occur in humans. METHODS: Iodine-123-labeled 3(R)-BMIPP and 3(S)-BMIPP isomers were injected at rest, on two separate days, in six patients with stable coronary artery disease. Dual-head, whole-body scintigraphy was performed 20 min and 3 hr after injection. SPECT cardiac imaging was performed 60 min after injection. RESULTS: Myocardial activity averaged (% injected dose +/- s.d.) 3.15 +/- 0.49 versus 3.01 +/- 0.44 at 20 min (p = ns) and 2.64 +/- 0.38 versus 2.55 +/- 0.41 at 3 hr postinjection (p = ns) for the 3(R)-BMIPP and 3(S)-BMIPP isomers, respectively. Liver activity averaged 9.50 +/- 1.18 versus 9.44 +/- 0.66 at 20 min and 5.33 +/- 0.64 versus 5.43 +/- 0.66 at 3 hr, respectively (p = ns). SPECT showed no difference in the distribution of the two isomers between normal and infarcted myocardium. CONCLUSION: There is no significant difference in myocardial and liver distribution of the 3(R)-BMIPP and 3(S)-BMIPP isomers in humans.     

Evaluation of the in vivo biodistribution of yttrium-labeled isomers of CHX-DTPA-conjugated monoclonal antibodies

We evaluated the in vivo stability and biodistribution of four isomers (CHX-A', CHA-A", CHX-B' and CHX-B") of 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriaminepentaaceti c acid (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA. METHODS: The ligands were conjugated to monoclonal antibody B3, a murine IgG1 kappa, and labeled with 88Y at 55.5-66.6 MBq/mg (1.5-1.8 mCi/mg). Nontumor-bearing nude mice were injected intravenously with 55.5-66.6 kBq (1.5-1.8 microCi) of 88Y-labeled B3 conjugates and with 125I-labeled B3 as an internal control. The mice were then killed at 6, 24, 48, 96 and 168 hr postinjection. RESULTS: At 168 hr, the concentration of 88Y in processed bone of either CHX-A' [4.6% injected dose (ID)/g] or CHX-A" (4.0%ID/g) was less than that of either the CHX-B' (21.9%ID/g) or B" (12.1%ID/g) ligands. The two ligands CHX-B" and CHX-B' were not acceptable for yttrium labeling of antibody because of their high and progressive bone accumulation. The accumulation of 88Y in bone of CHX-B' was five times greater than that of CHX-A' at 168 hr. The CHX-A" cleared from the circulation slightly faster than CHX-A' without releasing the yttrium and showed the lowest uptake by bone of any of the four isomers. The accumulation in the other normal organs was similar for all four isomers of 88Y-CHX-B3 conjugates. CONCLUSION: Although the CHX-B" and CHX-B' were not acceptable for labeling with yttrium, the CHX-A' and CHX-A" were suitable, indicating that differences in stereochemistry can greatly influence stability of radionuclide in the chelate.     

Preclinical evaluation of 111In-labeled B3 monoclonal antibody: biodistribution and imaging studies in nude mice bearing human epidermoid carcinoma xenografts

Biodistribution and imaging characteristics of monoclonal antibody B3 were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. B3 is a murine IgG1k, recently isolated, reacting with a carbohydrate epitope abundantly and uniformly expressed by most carcinomas. B3 was conjugated to a new backbone-substituted derivative of diethylenetriaminepentaacetic acid, 2-(p-isothiocyanato benzyl)-cyclohexyl-diethylenetriaminepentaacetic acid, and labeled with 111In. Tumor-bearing mice were given i.v. injections of approximately 5 microCi of either 111In-B3 or 111In-MOPC-21, an isotype-matched control, and sacrificed in groups of five at 6 h and daily up to 168 h. Imaging was performed at 24, 72, and 144 h. Significant differences were observed in tumor uptake at all time points with peak values at 48 h (25 +/- 5.2% versus 6.3 +/- 0.4% of the injected dose/g tissue) (mean +/- SD) for 111In-B3 and 111In-MOPC-21, respectively (P < 0.001). All tumor to organ ratios increased with time for 111In-B3. In particular, tumor:liver ratios rose from 3.2 +/- 0.6 at 24 h to 6.3 +/- 1.2 at 168 h. Imaging results showed selective and progressive accumulation of 111In-B3 at the tumor site, whereas 111In-MOPC-21 did not show specific localization. In summary, 111In-labeled B3 demonstrated good and specific tumor targeting, which warrants its future clinical evaluation.     

Autoantibodies to tissue transglutaminase as predictors of celiac disease

Our aim was to study the prognostic value of growth hormone (GH) -stimulated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP) score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7) with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were followed prospectively for three years. Six patients (40%) died during the follow-up period, of whom half had a CP score <9. Mean serum IGF-I levels 24 hr after rhGH injection (group 1 vs group 2, 17.4 +/- 6.8 vs 7.4 +/- 0.7 nmol/liter) predicted survival with 93% accuracy. Levels <10 nmol/liter portended a poor prognosis, with 15% survival at one year, whereas levels >10 nmol/liter had a 100% survival rate at one and two years, respectively. Baseline IGF-I (9.98 +/- 2.0 vs 6.38 +/- 0.8 nmol/liter), GHBP (9.2 +/- 3 vs 5.7 +/- 0.8%/50 microl), and IGFBP-3 serum levels at baseline (1.7 +/- 0.3 vs 0.86 +/- 0.2 mg/liter) and at 24 hr (2.04 +/- 0.38 vs 0.99 +/- 0.3 mg/liter) did not add to the predictive value of stimulated IGF-I levels at 24 hr and were less accurate in predicting the outcome in comparison to CP score (80%). We conclude that stimulated IGF-1 <10 nmol/liter may be a true predictor of a negative prognosis in patients with liver cirrhosis.     

Expression of tissue factor in hepatic ischemic-reperfusion injury of the rat

BACKGROUND: Tissue factor (TF) is a membranous protein normally present on the surface of the fibroblasts and smooth muscle cells of vessels. TF is an initiation factor for blood coagulation, and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response. We studied the significance of TF expression in warm ischemic-reperfusion injury of the liver using a rat model. METHODS: Following laparotomy of Lewis rats, the branches of the hepatic artery and portal vein leading to the median, left, and caudate lobes of the liver were clamped for 2 hr. The liver was reperfused after 120 min of ischemia. Rats were killed at 0, 1, 3, 5, 8, and 12 hr after reperfusion, and liver tissues were harvested. TF activity was measured by the chromophilic substrate S-2222. TF expression was studied by immunohistochemical staining with the monoclonal antibody HTF-K108. RESULTS: TF activity in the blood showed a peak at 3 hr after reperfusion (8.9+/-0.5 U/L), then decreased and returned to the normal level by 12 hr (0.9+/-0.3 U/L). TF activity in ischemic liver tissue increased gradually over 12 hr after reperfusion (1223+/-275 U/g dry weight before ischemia and 2545+/-284 U/g weight at 12 hr after reperfusion). Histologically spotty necroses were observed in the liver tissue 5 hr after reperfusion. The necrotic area extended and encompassed almost all of the ischemic liver by 12 hr after reperfusion. Histochemically, TF staining was negative on the hepatocytes and slightly positive on sinusoid cells of the normal liver. On the other hand, TF was strongly stained, especially on the hypertrophic monocytic cells accumulating at the site of the necrosis, but staining was not evident on the necrotic hepatocytes. A slight degree of TF staining was observed on the alveolar epithelium of the lung, irrespective of liver ischemia and reperfusion. CONCLUSION: These results demonstrate that TF plays an important role in the development of the hepatic ischemic-reperfusion injury, and the subsequent microcirculatory incompetence might cause the formation of microthrombus and the development of necrosis.     

Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800+/-3813 vs 6382+/-184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00+/-1.75 vs 0.28+/-0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631+/-2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55+/-0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.     

Misoprostol protection against acetaminophen-induced hepatotoxicity in the rat

The hepatoprotective effects of misoprostol on acetaminophen (APAP)-induced toxicity were studied in the rat. Liver injury was evaluated at 36 hr after APAP administration by measuring serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels, by using tetranitroblue tetrazolium (TNBT) staining and by histological analysis. After APAP administration, peak serum levels of the drug were detected at 15 min. Liver GSH was depleted from control levels of 448 +/- 48 micrograms/g to 82 +/- 2 micrograms/g (P < 0.01) within 3 hr. Serum ALT levels increased significantly after 16 hr and H&E staining revealed significant hepatic necrosis after 12 hr. Rats treated with misoprostol before and after APAP administration showed reduced OCT and ALT levels at 36 hr of overdose (454 +/- 446 IU/liter and 2571 +/- 2944 IU/liter, respectively) compared to those without misoprostol treatment (1348 +/- 480 IU/liter and 6077 +/- 3025 IU/liter, respectively, P < 0.01). TNBT staining showed a reduced area of damage from 28.6 +/- 22.3% to 7.3 +/- 8.9% (P < 0.01), and H&E staining also showed less extensive hepatic necrosis in rats treated with misoprostol before and after the overdose. In a time sequence study, misoprostol treatment starting within 10 hr of overdose showed the same protective effect as when it was given before and after APAP ingestion. No protection was detected when the treatment was started during the development of hepatic injury. However, misoprostol given when injury was established seemed to be protective. Our results show that misoprostol protects the liver against APAP-induced injury if given within 10 hr of overdose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Imaging experimental infective endocarditis with indium-111-labeled blood cellular components

The capability of radionuclide imaging to detect experimental aortic valve infective endocarditis was assessed with indium-111 (111In)-labeled blood cells. Sequential cardiac imaging and tissue distribution studies were obtained in 17 rabbits with infective endocarditis after administration of 111In-platelets and in five after 111In-polymorphonuclear leukocytes. Forty-eight to 72 hours after platelet administration, in vivo imaging demonstrated abnormal 111In uptake in all animals in the region of the aortic valve in an anatomically distinct pattern. Images of the excised heart showed discrete cardiac uptake conforming to the in vivo image and gross pathological examination. 111In platelet uptake in vegetations from the 17 animals averaged 240 +/- 41 times greater than that in normal myocardium and 99 +/- 15 times greater uptake in blood. In contrast, 111In-leukocyte cardiac imaging showed no abnormal aortic valve uptake 24 hours after tracer administration and the lesion myocardium activity ratio was only 5 +/- 2 (3 +/- 1 for lesion/blood activity). Four normal rabbits demonstrated neither positive 111In platelet scintigraphs nor abnormal cardiac tissue uptake. Likewise, noncellular 111In was not concentrated to any significant extent in three animals with infective endocarditis. This study demonstrates that 111In platelet, but not leukocyte cardiac imaging, is a sensitive technique for detecting experimental infective endocarditis. The imaging data conform to the cellular pathology of the infective endocarditis vegetation.     

Dual contrast enhancement of both T1- and T2-weighted sequences using ultrasmall superparamagnetic iron oxide

BMS 180549 (previously AMI-227), an ultrasmall superparamagnetic iron particulate agent, was investigated to determine its utility as a contrast agent on T1-weighted, as well as T2-weighted sequences, as a function of route of administration, (intravenous versus selective arterial) and concentration. Twelve farm pigs were divided into three groups of four each by route of administration (intravenous, selective superior mesenteric, or selective hepatic arterial injection). 10 mumol/kg and 20 mumol/kg dosages were given and evaluated both immediately after and 20-24 hr after contrast infusion, using both spin-echo and gradient-echo T1 and T2-weighted sequences. Significant postcontrast liver and spleen enhancement was noted at both concentrations, regardless of route of administration on both T1- and T2-weighted sequences. The earliest postcontrast T1-weighted sequence obtained during the 1-3 min interval following IV administration of high dose (20 mumol/kg) contrast demonstrated an average of +42.8% liver and +249.0% spleen enhancement; 24 hr later this decreased to 0 and 7.2%, respectively. The earliest postcontrast T2-weighted sequence obtained during the 8-17 min interval post high-dose IV contrast showed an average of -75.8% decrease in liver and -28.7% decrease in spleen signal intensity; 24 hr later the magnitude of these changes diminished to -33.1% and +2.5%, respectively. No significant difference was noted in liver or spleen enhancement, regardless of route of contrast administration (intravenous versus intraarterial).     

The results of questionnaire on quantitative assessment of 123I-metaiodobenzylguanidine myocardial scintigraphy in heart failure

This study was done by working group under the cooperation between Japanese Society of Nuclear Medicine and Japanese Circulation Society. We evaluated the usefulness of quantitative assessment of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in heart failure by the results of questionnaire. Forty-nine (72.1%) of 68 selected institutions participated in this study. The incidence of MIBG myocardial scintigraphy used in heart failure was 41.1%. The imaging protocol was mostly done by both planar and SPECT at 15 min and 3.6 hr after intravenous injection of 111 MBq of MIBG. The quantitative assessment was mostly done by heart/mediastinum (H/M) ratio and washout rate analysis based on planar imaging. The mean normal value of H/M ratio were 2.34 +/- 0.36, and 2.49 +/- 0.40, at early and delayed images, respectively. The normal value of washout rate was 27.74 +/- 5.34%. On the other hand, those of H/M ratio in heart failure were 1.87 +/- 0.27, and 1.75 +/- 0.24, at early and delayed images, respectively. That of washout rate was 42.30 +/- 6.75%. These parameters were very useful for the evaluation of heart failure. In conclusion, MIBG myocardial scintigraphy was widely used for not only early detection and severity assessment, but also indication for therapy and prognosis evaluation in heart failure patients.     

Relationship between symptoms of jumper''s knee and the ultrasound characteristics of the patellar tendon among high level male volleyball players

In this study we investigated the applicability of 99mTc-labeled CD19 monoclonal antibody (mAb) for tumor imaging in patients with B cell non-Hodgkin's lymphoma. A 1-mg sample of murine CD19 mAb was labeled with approximately 550 MBq [99mTc]pertechnetate. The labeled mAb was administered i.v. to seven patients, four without and three with pretreatment with 10 mg unlabeled CD19 mAb. The number of circulating B cells was decreased by 44 +/- 5% 1 h after injection of the radiolabeled mAb. Peripheral B cells were coated with CD19, resulting in partial modulation of CD19, most pronounced in the three pretreated patients. Whole-body images were obtained with a gamma camera and compared with results obtained by conventional imaging techniques. Initially, blood-pool activity dominated, whereas 24 h after injection the radioactivity was mainly located in the spleen, kidneys and liver. In two patients, a lesion in the spleen appeared as an unlabeled spot. In one patient, a lesion in the femur, which was detected by computed tomography (CT) and gallium-67 scans, was also seen on the CD19 scan from 1 h after administration of the radioimmunoconjugate onwards. Good imaging of bone marrow infiltration was observed in one of three patients. Lymph node involvement was not observed in any of the patients in whom affected lymph nodes were detected by CT or gallium-67 scan. In conclusion, in the present study radioimmunodetection with 99mTc-labeled CD19 mAb was found to be inferior to CT and gallium-67 scanning in the diagnosis of patients with B cell non-Hodgkin's lymphoma.