Proximal sciatic axotomy does not inhibit the induction of neurofilamentous inclusions following intracisternal aluminum chloride exposure

The present study evaluated 99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to 99mTc(III) DMSA and 99mTC-HIG. All three radiopharmaceuticals were prepared with commercial kits. 99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 microliters turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1, 3, 6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with 99mTc(V) DMSA compared to 99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with 99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 +/- 3.20 (24 h), 4.19 +/- 1.39 (6 h) and 5.98 +/- 1.17 (24 h) and max. abscess/blood ratios were 6.22 +/- 1.41, 4.09 +/- 0.84 and 0.914 +/- 0.351 all at 24 h for 99mTc(V) DMSA, 99mTc(III) DMSA and 99mTc-HIG, respectively. Experimental arthritis was produced in New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of 99mTc(V) DMSA and 99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROI's over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 +/- 0.31 (3 h) and 2.92 +/- 0.99 (24 h) for 99mTc(V) DMSA and 99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with 99mTc(V) DMSA.     

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.     

Impingement syndrome following total shoulder arthroplasty and humeral hemiarthroplasty: treatment with arthroscopic acromioplasty

In this pilot study, 99Tcm-labelled human immunoglobulin G (99Tcm-HIG) was evaluated as a lymphoscintigraphic agent in five rabbits. It was injected intradermally into the web space of the hind legs of the rabbits (37 MBq/0.1 ml). Sequential scintigrams were obtained using a gamma camera for 120 min. The injection site and the hind legs were massaged post-injection. Blood samples were obtained at 5, 15, 30, 60, 90 and 120 min. Two of the rabbits were killed after 2 h. Their organs were weighed and tissue specimens were obtained, weighed and counted against a standard using a gamma counter. The lymph channels and the lymph nodes were well visualized on the scintigrams. The background activity was very low, making interpretation easier. About 30% of the injected dose migrated from the injection site by 2 h. The mean popliteal lymph node uptake was 5.71 +/- 4.62% per gram of tissue. The lymph node to other tissue concentration ratios were very high, ranging from 63:1 for the kidneys to 1099:1 for the heart. We conclude that 99Tcm-HIG is a promising new agent for the visualization of the lymphatic system due to its easy labelling procedure, the stability of the label, its widespread availability and good image quality. It may potentially be useful in detecting and evaluating inflammatory lymph nodes.     

Retention of insoluble particles after local intrabronchial deposition in dogs

Recent studies have challenged the generally accepted hypothesis that bronchial particle clearance is complete within 24-48 h postdeposition. We studied bronchial retention of inert particles using a bronchoscope and microspray nozzle to localize deposition in a bronchus while avoiding alveolar deposition. Six-microliter aliquots (444 kBq) of submicrometer (number mean diameter = 0.22 microns, geometric standard deviation = 1.75) technetium-99m-labeled (99mTc) sulfur colloid (SC) particles (n = 6) or the unbound radiolabel 99mTc-pertechnetate (99mTcO4-; n = 3) were sprayed onto a 5-mm-diam bronchus in halothane-anesthetized dogs. Radioactivity at the deposition site and clearance pathway was monitored externally with a gamma camera beginning immediately postspray. Bronchial retention of SC was 8.5 +/- 2.4 and 1.5 +/- 0.7% at 3 and 24 h postspray, respectively. Tracheal mucus velocity was measured at 10.4 +/- 2.2 mm/min. For comparison, clearance of inhaled submicrometer SC particles was also measured in the same dogs. Retention of inhaled aerosolized SC (peripheral lung deposition) was 98.1 +/- 1.1 and 76.3 +/- 1.8% at 3 and 24 h, respectively. 99mTcO4- cleared from the bronchi slightly more rapidly than did SC. Radioactivity was readily detected in the blood after deposition of 99mTcO4- but not of SC. Thus SC cleared by mucociliary transport, whereas 99mTcO4- cleared predominantly by transepithelial absorption. We conclude that clearance of submicrometer particles from a 5-mm conducting airway is very nearly complete by 24 h, with approximately 92% of the clearance occurring within the first 3 h postdeposition.     

Competent transcription initiation by RNA polymerase II in cell-free extracts from xeroderma pigmentosum groups B and D in an optimized RNA transcription assay

99Tcm-glucarate accumulation in human mammary BT-20 tumours hosted in severe combined immune deficiency (SCID) mice was compared to 111In-monoclonal antibody 103D2-F(ab')2, 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) and 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA). The intracellular tumour distribution of 99Tcm-glucarate was also determined. SCID mice injected with a mixture of 99Tcm-glucarate and 111In-103D2-F(ab')2 were imaged serially up until 24 h. Computer planimetered tumour-to-blood activity (in the heart) ratios (T/BH) to 8 h were significantly greater for 99Tcm-glucarate than 111In-103D2. The mean (+/-S.D.) tumour-to-blood ratio (T/B) from biodistribution was 1.21 +/- 0.31 and 0.35 +/- 0.06 (P < 0.0001) at 5 h, and 1.526 +/- 0.29 and 0.75 +/- 0.2 (P < 0.0001) at 8 h, for 99Tcm-glucarate and 111In-103D2 respectively. At 24 h, T/B for 111In-103D2 (1.76 +/- 0.22) exceeded that of 99Tcm-glucarate (1.44 +/- 0.2, P = 0.01). 99Tcm-glucarate uptake in the tumours at 5 h (1.133 +/- 0.25 %ID g-1) and 8 h (1.213 +/- 0.23 %ID g-1) was significantly greater than that of 99Tcm-MIBI (0.340 +/- 0.09, P = 0.0002; 0.220 +/- 0.04, P = 0.0001) and 99Tcm-DTPA (0.091 +/- 0.03, P < 0.0002; 0.016 +/- 0.01, P < 0.0001) respectively. Intracellular tumour distribution of 99Tcm-glucarate was 50.91 +/- 6.55% in the nuclear fraction, 34.34 +/- 2.88% in the cytoplasmic fraction and 14.75 +/- 7.66% in the mitochondrial fraction. Thus glucarate may provide a 99Tcm-based mammary tumour imaging modality for visualization of tumours very quickly after tracer administration with maximal targeting in the nuclei of the tumour cells.     

Uptake of 67Ga in the lactating breast and its persistence in milk: case report

The concentration of 67Ga in the milk of a postpartum woman was measured at intervals up to 8 days after the injection of 3 mCi of 67Ga-citrate. The 67Ga concentration was about 0.15 muCi/ml at 3 days after injection and fell to 0.035 muCi/ml by 8 days. Since the biologic clearance of gallium was slow (T1/2 approximately 9 days), the major determinant of the clearance of radioactivity was the physical decay of the gallium. An estimate of the radiation dose to a nursing infant suggests that nursing be interrupted for about 2 weeks after the mother has had a 67Ga study.     

Functional study of the sick-sinus syndrome in patients with chronic Chagasic cardiopathy

In seven healthy male volunteers the effects of the pattern of dosing on the pharmacokinetics of diazepam have been studied. A cross-over design was employed that consisted of three parts: a single intravenous dose (0.1 mg/kg), and oral dosing (10 mg/day) for six days followed by an intravenous bolus (0.1 mg/kg) on the seventh day, followed by re-examination of a single intravenous dose after diazepam (D) and its major metabolite desmethyldiazepam (DD) had been completely eliminated. Plasma levels of D and DD were monitored by a specific, sensitive GLC-method. In younger patients (n = 5, age 29 - 35 years) the elimination half-life, T1/2(beta), of D was 33.9 +/- 10.6 h (mean +/- S.D.) after the single dose. The control study gave an almost identical result (35.7 +/- 12.1). After subchronic dosage in all patients T1/2(beta) showed a modest but significant prolongation (paired t-test p less than 0.01) to 52.9 +/- 17.4 h. It was caused by a significant decrease (p = 0.016) in total plasma clearance (Cl), from 26.0 +/- 10.8 ml/min. Older patients (age 43-60 years) showed the same phenomenon. Blood/plasma ratios remained constant indicating no change in protein binding. Biliary excretion of D was measured in five patients with a T-tube. Only negligible amounts (0.3 - 0.4%) of administered D were excreted within 3 days after subchronic dosage, which demonstrates a lack of enterohepatic cycling of D. After multiple administration of D, there was accumulation of DD to levels approximately five times higher than after a single dose. The possibility that the slower elimination of D after subchronic treatment might be caused by DD was also supported by experiments in dogs and rabbits. After pretreating rabbits with DD and maintaining a high DD plasma level, there was prolongation of T1/2(beta) from 2.7 h to 5.2 h, with a corresponding decrease of Cl from 101.6 ml/min to 23.4 ml/min. Similar results were obtained in dogs. It is concluded that the disposition of D is altered by subchronic use and may be regulated by the plasma DD concentration.     

Excretion of endogenous and exogenous purine derivatives in sheep: effect of increased concentrate intake

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.     

Effect of detergent combined with large tidal volume ventilation on alveolocapillary permeability

The combined effect of large tidal volume ventilation (LTVV) and detergent-induced surfactant dysfunction on the clearance kinetics of technetium-99m-labelled diethylene triamine pentaacetate was investigated. Four groups of rabbits (n = 6 in each) were studied: (1) controls, (2) detergent, (3) LTVV, and (4) detergent + LTVV. Clearance was measured for 3 h and the kinetics was analysed by fitting mono- and biexponential equations to the clearance curve and was expressed as a half-life (T 1/2). Pulmonary clearance of 99mTc-DTPA was monoexponential in control animals (T 1/2 = 194 min) and in animals ventilated with LTVV (T 1/2 = 43 min, P < 0.01 compared with controls). In contrast, clearance was biexponential after detergent administration with or without LTVV. T 1/2 values of the fast and slow compartments were 5.4 and 80 min, respectively, with the fast fraction comprising 81% of the radioactivity after detergent alone. When detergent was combined with LTVV, clearance was bicompartmental as with detergent alone, with the same size of the fast fraction. However, clearance from each of the slow (P < 0.01) and fast compartments (P < 0.05) increased significantly. Clearance from the slow compartment was thus similar to T 1/2 during LTVV alone. Large tidal volume ventilation induced a faster than normal clearance of a single compartment, whereas detergent induced kinetics that was distinctly bicompartmental. The mechanisms increasing permeability of the alveolocapillary barrier after detergent and during LTVV seem different and may be additive.     

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals

OBJECTIVES: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. SUBJECTS: Ten adult male New Zealand rabbits. INTERVENTIONS: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. MEASUREMENTS AND MAIN RESULTS: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). CONCLUSIONS: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.     

Influence of the heterogeneity of P-glycoprotein expression on technetium-99m-MIBI uptake in breast cancer

We prospectively studied a total of 30 patients with breast cancer to evaluate the relationship between the degree of accumulation of 99mTc-sestamibi (MIBI) and the heterogeneity of p-glycoprotein expression in tumor tissues. METHODS: Twenty patients during initial presentation and 10 patients during post-therapy evaluation underwent contemporaneous 99mTc-MIBI imaging and surgery or biopsy. Immunohistochemical studies were performed on multiple nonconsecutive sections of the same tumor using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor-to-background (T/B) ratios were correlated with the level and heterogeneity of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak expression (Group 2) or those with weak-to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06, respectively). There was statistically significant difference in T/B ratios between all 3 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clearly distinct from one another with no overlapping values, the values for Group 2 overlapped with those of Group 1 and Group 3. When we evaluated the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obtained a stronger correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus 0.735). CONCLUSION: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and 99mTc-MIBI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p-glycoprotein is not extensively explored. Although our data confirmed that 99mTc-MIBI imaging is useful in the determination of the presence of multidrug resistance in patients with breast cancer, the issue of heterogeneous expression of the antigen should be further investigated when unexpected results are obtained.     

Comparison of technetium-99m-ll-EC isomers in rats and humans

Technetium-99m-L,L-ethylenedicysteine (99mTc-LL-EC) is a new renal imaging agent with pharmacokinetic properties reported to be slightly superior to those of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3); however, to better define the potential of the enantiomer 99mTc-DD-EC and the diastereomer 99mTc-DL-EC as renal imaging agents, we compared the three EC stereoisomers with 131I-orthoiodohippurate (OIH) in a series of rats and humans. METHODS: Each 99mTc-EC stereoisomer was coinjected with OIH in six Sprague-Dawley rats for measurements of clearance and extraction fraction. Each stereoisomer was also coinjected with OIH in three human volunteers followed by sequential imaging, plasma clearance measurements and timed urine collections. RESULTS: Technetium-99m-DD-EC had the highest clearance and extraction efficiency in rats (p < or = 0.02). In humans, image quality was good with all three agents. The clearance ratio (EC/OIH) was 82% +/- 8% for 99mTc-DD-EC compared to 70% +/- 3% and 40% +/- 5% for 99mTc-LL-EC and 99mTc-DL-EC, respectively. Technetium-99m-DD and 99mTc-LL-EC were excreted more rapidly than 99mTc-DL-EC. CONCLUSION: Technetium-99m-DD-EC has excellent imaging properties and the data suggest that its clearance may approach that of OIH more closely than any other 99mTc renal agent. A potential limitation is the fact that both 99mTc-DD and LL-EC exist in dianionic (80%) and monoanionic (20%) forms at physiological pH and it is unlikely that these two forms have the same clearance or protein binding affinity.     

Rupture of rudimentary horn pregnancy: a case report

OBJECTIVE: The aim of this study was to develop a method for measuring renal function with 99mTc-MAG3 gamma-camera renography without blood or urine sampling and evaluate its feasibility. PATIENTS, MATERIAL AND METHODS: Twelve patients with nephrological disorders underwent 99mTc-MAG3 renography and para-aminohippurate clearance measurement. Plasma clearance of 99mTc-MAG3 (ClMAG) was calculated through early renal uptake of 99mTc-MAG3 after appropriate correction of parameters (background, measured attenuation coefficient of 99mTc, and the actual depth of kidneys measured with computed tomography), and on one-compartment assumption of the kinetics of 99mTc-MAG3. We compared the resultant ClMAG with standard effective renal plasma flow (ERPF), using the para-aminohippurate clearance method and with simulated ClMAG derived from the two-compartment model. RESULTS: ClMAG calculated by the one-compartment model (283+/-131 ml/min, mean +/- SD) correlated with ERPF (r = 0.94, p <0.001), and was similar to the simulated ClMAG estimated from the two-compartment model in all patients (283+/-139 ml/min). CONCLUSION: This alternative method, which employs theoretical modeling of the pharmacokinetics of 99mTc-MAG3, may provide easy, noninvasive measurement of individual renal function without blood sampling or in vitro equipment. Further studies should be warranted.     

Scientific challenges in environmental carcinogenesis

Myocardial uptake of iodine-123 meta-iodobenzylguanidine (123I-MIBG) was measured using scintigrams at rest in 12 patients with isolated, nonischemic mitral regurgitation (MR; regurgitant fraction 64% +/- 7%) and was related to the left ventricular (LV) function assessed by cardiac catheterization. Iodine-123 meta-iodobenzylguanidine activity in the upper mediastinum, liver, and lung was comparable between MR and control (n = 8) patients. The heart-to-mediastinum 123I-MIBG activity ratio 4 hours after injection was significantly (p < 0.01) decreased in MR (2.0 +/- 0.1, mean +/- SE) compared with control (2.7 +/- 0.1) with the increased clearance of MIBG. In addition, MR patients had significantly greater heterogeneity in the 123I-MIBG distribution within the myocardial images (26.1% +/- 2.1% intraimage variability for MR versus 15.6% +/- 0.8% for control, p < 0.01). Myocardial 123I-MIBG activity correlated positively with cardiac index and negatively with pulmonary capillary wedge pressure and LV volume indexes. Thus, 123I-MIBG scintigrams can be a noninvasive method for assessing the contractile dysfunction in MR.     

Clearance of technetium 99m N-NOET in normal, ischemic-reperfused, and membrane-disrupted myocardium

BACKGROUND: Technetium 99m-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) (99mTcN-NOET) is a new neutral cardiac perfusion imaging agent that has been shown to have very high uptake and retention in vitro. The purpose of this study was to determine the clearance kinetics of 99mTcN-NOET in control, ischemic-reperfused, and membrane-disrupted myocardium. METHODS AND RESULTS: After a 100 microCi (3.7 x 10(6) Bq) bolus of 99mTcN-NOET was injected, myocardial clearance was monitored for 1 hour by the use of a sodium iodide detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts. Seven hearts were used as controls (group 1). In seven ischemic-reperfused hearts, tracer administration and uptake was followed by 30 minutes of no flow and 1 hour of reflow (group 2). In six additional ischemic-reperfused hearts, tracer administration was followed by deprivation of flow for 1 hour followed by 1 hour of reflow (group 3). Six hearts were perfused with a 0.5% Triton X-100 KH perfusate for 1 hour (group 4). Four hearts were perfused with KH for 10 minutes, followed by cyanide for 10 minutes (group 5). This cycle was repeated three times. Activities remaining in each heart at the end of each experiment were quantitated, and activity at peak uptake was calculated. The 99mTcN-NOET myocardial clearance was near linear in the control (0.6 +/- 0.4) and both ischemic-reperfused groups with virtually no fractional clearance (1.2% +/- 0.6% and 2.1% +/- 0.6%, respectively; p = NS). In the Triton X-100 membrane-disrupted hearts, clearance was substantial (94.2% +/- 4.0%; p < 0.0001 compared with the control and ischemic-reperfused groups). Cyanide treatment produced rapid clearance, which was arrested by a return to the standard KH perfusate. Peak uptake as a percentage of injected dose was 74.9% +/- 1.4% for all groups combined. CONCLUSION: Thus 99mTcN-NOET has extremely high myocardial retention after 1 hour in normal myocardium and is not significantly affected by ongoing myocardial ischemia or reperfusion injury in this model. Clearance is increased markedly in extreme conditions of membrane disruption. These data are consistent with the concept that 99mTc-NOET is localized predominantly in or on cell membranes. 99mTcN-NOET is a promising, new myocardial perfusion imaging agent that exhibits a stable myocardial distribution in the setting of acute developing injury.     

The effect of CY1503, a sialyl Lewisx analog blocker of the selectin adhesion molecules, on infarct size and "no-reflow" in the rabbit model of acute myocardial infarction/reperfusion

CY1503, an analogue of sialyl-Lewisx, is an inhibitor of the selectin adhesion molecules. CY1503 has been found to limit myocardial infarct size in canine and feline models. However, the effect of CY1503 on the "no-reflow" phenomenon is still unknown. Anesthetised rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. Protocol 1: after 27 min of ischemia, rabbits were randomised to an iv bolus of either CY1503 (30 mg/kg) (n=9) or saline (n=9). Protocol 2: rabbits were randomly given two iv boluses of CY1503 (30 mg/kg) (n=6) or saline (n=6), administered after 10 and 25 min of ischemia. Protocol 3: after 27 min of ischemia rabbits were randomly given an iv bolus of CY1503 (30 mg/kg) (n=6) and infusion of 20 mg/kg over 4 h or saline bolus+infusion (n=6). Regional myocardial blood flow (RMBF) was assessed after 30 min and 4 h of reperfusion. The risk zone (RZ) was assessed by blue dye and the necrotic zone (NZ) by tetrazolium staining. RMBF: protocol 1: RMBF in the RZ was 2.19+/-0.33 v 2. 34+/-0.34 ml/g/min in CY1503 and controls at 30 min (P=0.75), and 0. 43+/-0.07 v 0.41+/-0.08 at 4 h of reperfusion (P=0.85). The corresponding results for protocol 2 were 1.77+/-0.29 v 1.53+/-0.34 at 30 min (P=0.61) and 0.53+/-0.16 v 0.91+/-0.55 at 4 h (P=0.53). RMBF in RZ in protocol 3 were 1.52+/-0.25 v 1.32+/-0.20 at 30 min (P=0.56) and 0.30+/-0.05 v 0.29+/-0.09 (P=0.90) after 4 h of reperfusion. The RZ was similar in both groups in all protocols. The NZ/RZ ratio was comparable in the CY1503 and control group in all three protocols (0.32+/-0.04 v 0.37+/-0.06, 0.37+/-0.08 v 0.33+/-0. 07, and 0.51+/-0.05 v 0.38+/-0.05 in protocols 1, 2, and 3, respectively). CY1503 did not limit infarct size or prevent the "no-reflow" phenomenon in the rabbit.     

Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.     

Isolation and characterization of mitochondria from turkey spermatozoa

The purpose of the present investigation was to evaluate 99Tcm-labelled alpha-D-glucose 1-phosphate (GP) aerosols for single photon emission computed tomographic (SPECT) ventilation lung imaging in comparison to 99Tcm-diethylenetriaminepentaacetate (DTPA) aerosols. Ten normal nonsmoking male volunteers (aged 20-30 years) were included in this study after obtaining their informed consent. 99Tcm-GP, 30 mCi, in 2 ml was placed in the nebulizer (Venticis II) and inhalation continued for 5 min of normal breathing with oxygen flowing through. In 10 subjects dynamic images were obtained from the posterior position for 90 min with 45 frames on a 64 x 64 matrix by the use of a gamma camera. At the end of the dynamic study planar images of the lung (anterior, posterior and laterals) were recorded. Decay corrected clearance curves and kep values were obtained by the pulmonary epithelial programme and T1/2 values were calculated. The same procedure was followed by the use of 99Tcm-DTPA in the same subjects 2 weeks later. SPECT studies of the lung were performed in five subjects after inhalation of 99Tcm-GP aerosols. Clearance curves were monoexponential. The difference in T1/2 values between the right and left lungs was statistically insignificant (P > 0.10). The mean T1/2 values were 316.5 +/- 44.7 and 80.8 +/- 13.4 min for 99Tcm-GP and 99Tcm-DTPA, respectively. The difference was significant (P < 0.0005). On scintigraphic images 99Tcm-GP showed high alveolar deposition and low adhesion to major airways like 99Tcm-DTPA. However, it is preferred to 99Tcm-DTPA for SPECT studies because of its prolonged pulmonary clearance.     

Middle ear carcinoid: an indolent tumor with metastatic potential

5-lodo-2'-deoxyuridine (IUdR), a thymidine analog, is transported through cell membrane and is incorporated into newly synthesized DNA during the S phase of mitotic cells. In rapidly growing brain tumors such as glioma, radioiodinated IUdR may be an efficient diagnostic as well as therapeutic agent and may provide a means to determine the proliferative activity of the tumor. IUdR was labeled with 123I (t1/2 = 13.3 h, gamma = 159 KeV, 83%) and injected i.v. into nude mice bearing human colorectal carcinoma LS174T. At 3 and 20 h postinjection, tumor uptake was 2.6 +/- 0.9% and 0.5 +/- 0.2%, respectively, of the injected dose per gram of tissue. Radioactivity in other tissues also declined as a function of time, but much more rapidly, yielding tumor-to-blood ratios of 16.4 +/- 2.2 and tumor-to-muscle ratios of 22.2 +/- 7.7 at 20 h postinjection. Of the radioactivity in the tumor, 12.6 +/- 0.9% was bound to DNA at 3 h and 25.2 +/- 2% at 20 h postinjection. A high (7 +/- 1.1% i.d.) uptake in thyroid at 3 h postinjection indicated dehalogenation in vivo.     

Stress and the immune system: preliminary observations in rheumatoid arthritis using an in vivo marker of immune activity

This study measured volumetric liver blood flow and galactose clearance concurrently during orthotopic liver transplant in human subjects. Ultrasound transit time flowmeters measured hepatic artery and portal vein flow 1-3 h after reperfusion. Galactose (100 mg/min) was infused over 45-60 min to steady state for calculation of clearance. Mean +/- S.D. total volumetric flow was 1966 +/- 831 ml/min with portal flow contributing 86%. Mean galactose clearance was 1988 +/- 641 ml/min. There was a significant correlation (p < 0.05, r = 0.61) between volumetric total liver blood flow and galactose clearance. The data show that: (i) the newly transplanted liver is capable of metabolizing galactose within 1-3 h of reperfusion; and (ii) liver blood flow is high in the newly implanted liver. The clinical importance of this observation is that there is increased clearance of high first pass substances by the transplanted liver which may be of importance in patient management.