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Biomedical subjects

J Machac

Publications and source records attributed to J Machac.

At least 37 records · Page 2Linked to original sources

Short course therapy with cefuroxime axetil for acute otitis media: results of a randomized multicenter comparison with amoxicillin/clavulanate.

BACKGROUND: Otitis media is a common infection of childhood. Increasing antibiotic resistance rates among the principal causative pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are associated with failure of first line agents. OBJECTIVE: This open, randomized, multicenter study compared the clinical efficacy of a short 5-day course of cefuroxime axetil (CAE) suspension with that of amoxicillin/clavulanate (A/CA) suspension for 8 or 10 days. METHODS: Children age 6 to 36 months with acute otitis media with effusion, diagnosed by tympanocentesis and microbiologic culture, were randomized to receive CAE (30 mg/kg/day in two divided doses for 5 days) or A/CA 40 mg/kg/day in three divided doses for 10 days (A/CA-10). In French centers A/CA was given at 80 mg/kg/day in three divided doses for 8 days (A/CA-8). Patients were assessed 1 to 4 days after completing the course (posttreatment) and followed up at 21 to 28 days after completing the course. RESULTS: Of the 716 patients randomized, 252 were treated with CAE, 255 with A/CA-10 and 209 with A/CA-8. In the clinically evaluable population, the proportions of patients with clinical cure at posttreatment were 175 of 203 (86%), 181 of 205 (88%) and 145 of 164 (88%) in the CAE, A/CA-10 and A/CA-8 groups, respectively, demonstrating equivalence among the three treatments. For patients <18 months old, clinical cures were 111 of 134 (83%), 116 of 131 (89%) and 83 of 99 (84%) in the CAE, A/CA-10 and A/CA-8 groups, respectively; equivalence was also demonstrated. At follow-up, 130 of 175 (74%) CAE, 121 of 172 (70%) A/CA-10, and 112 of 142 (79%) A/CA-8 had maintained cure. A total of 837 pretreatment pathogens were isolated from middle ear fluid in 73% (522 of 716) patients, the majority of isolates were S. pneumoniae (30%) and H. influenzae (27%). The most common adverse events were gastrointestinal, the incidence of drug-related diarrhea being higher in the A/CA-10 group (18%) than in either the CAE or A/CA-8 groups (10%). CONCLUSIONS: A 5-day course of CAE, given twice daily, was shown to be equivalent to the two regimens of A/CA for treatment of acute otitis media with effusion in children.

Acute Disease↗

Improvement of the fluorine-18 fluorodeoxyglucose images in simultaneous F-18 FDG/Tc-99m collimated spect imaging.

Collimated F-18 FDG SPECT imaging has been shown to be an acceptable alternative to F-18 FDG PET imaging for evaluating injured but viable myocardium. Ultra-energy (UHE) imaging is usually performed in simultaneous F-18 FDG/Tc-99m MIBI studies. The main limitations of this technique are degradation of the Tc-99m MIBI images due to F-18 downscatter to the Tc-99m window, and loss of resolution in Tc-99m images caused by using a UHE rather than a low-energy collimator. The quality of F-18 images has not been addressed. In our clinical and phantom studies we have found that F-18 images are inferior to simultaneously acquired Tc-99m MIBI images. This paper compares two correction methods for F-18 FDG images in a realistic cardiac phantom study. One approach is subtractive scatter correction, which employs a third 410 keV energy window image to estimate scatter. The other approach is based on restoration. The phantom acquisition was performed with 7.2 MBq of F-18 and 22.2 MBq of Tc-99m injected into the left ventricular (LV) wall. Three inserts, 3 cm, 2 cm, and 1 cm in diameter, were placed in the LV wall to simulate infarcts. Circumferential profiles were drawn from three successive short-axis slices and compared with true phantom data. The differences were calculated as root-mean-square error (rmse). Scatter correction improved rmse only 4.5 +/- 0.3%, while restoration improved rmse 16.1 +/- 0.4%, when compared with raw data. The same differences, measured as rmse, were 9.5 +/- 0.5, 6.8 +/- 0.4, and 5.1 +/- 0.5 for raw, scatter corrected, and restored F-18 data, respectively, when compared with Tc-99m window 140 keV data. The amount of noise, measured as root-mean-square % (rms%) was 5.3 +/- 0.5% for the Tc-99m image, 4.9 +/- 0.7% for the F-18 restored image, 6.2 +/- 0.6% for the raw F-18 image, and 6.5 +/- 0.9% for the scatter corrected F-18 image. The contrast measured for 2 cm and 3 cm inserts was 0.17 +/- 0.07 and 0.26 +/- 0.06 for F-18 raw data, 0.19 +/- 0.08 and 0.29 +/- 0.06 for the scatter corrected F-18 image, and 0.28 +/- 0.06 and 0.43 +/- 0.07 for the restored F-18 image. The contrast was 0.20 +/- 0.07 and 0.46 +/- 0.05 for the Tc-99m 140 keV window image. The restoration approach provided F-18 images of better contrast and detectibility than uncorrected or scatter corrected F-18 images. Restored F-18 images match better with the simultaneously acquired Tc-99m images.

Biophysical Phenomena↗

Effect of long-term eprosartan versus enalapril antihypertensive therapy on left ventricular mass and coronary flow reserve in stage I-II hypertension. Eprosartan Study Group.

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Acrylates↗

A transformation cross-talk technique for simultaneous dual radionuclide imaging: a myocardial perfusion 201Tl/99Tcm sestamibi dog SPECT study.

We have developed a novel transformation method for the correction of cross-talk in simultaneous dual radionuclide single photon emission CT (SPECT) imaging. It is based on the assumption that the transformations, which transform the primary energy window images into the scatter images as viewed in the other energy windows, are known. The method was tested on a dog model. These transformations were found by measuring the point response functions (prf) in different energy windows for both radionuclides in water. The dual radionuclide correction method described takes into account the different spatial distributions of the primary and scatter cross-talk photons in different energy windows. This method also includes the sequential application of restoration filters to the resulting cross-talk corrected images. We used a dog model in three separate studies: two single radionuclide studies used as references and one dual radionuclide study. Contrast between the left ventricular cavity (LVC) and the myocardium was used in horizontal long axis (HLA) slices as a parameter to evaluate the results of the dual radionuclide correction method with restoration. The increase of the contrast in the dual radionuclide corrected images in both energy windows, i.e. 201Tl primary window (70 keV) and 99Tcm primary window (140 keV), was significant. The cross-talk corrected 70 keV dual radionuclide HLA slice had a contrast of 0.62 compared with 0.35, which was the value in the non-corrected dual radionuclide HLA slice. Restoration improved the contrast to 0.68. In the single radionuclide 201Tl image, the same contrast was 0.59, improving to 0.70 after restoration. For the dual radionuclide 140 keV HLA slice, the contrast increased from 0.69 to 0.76 after cross-talk correction. Additional increase of the contrast to 0.83 resulted from restoration filtering. In the single radionuclide 99Tcm sestamibi 140 keV HLA slice the improvement of contrast was from 0.63 to 0.86 as a result of the restoration. The transformation three-window, dual radionuclide correction method with restoration improves the quality of the simultaneous rest 201Tl/stress 99Tcm sestamibi SPECT imaging.

Animals↗

Differential in vivo recovery of sinusoidal endothelial cells, hepatocytes, and Kupffer cells after cold preservation and liver transplantation in rats.

BACKGROUND: The injury resulting from cold preservation/reperfusion primarily affects sinusoidal endothelial cells, while hepatocytes are thought to be less vulnerable; morphological changes and increased cytokine release suggest that Kupffer cells are activated. We evaluated the extent of functional damage to the different cell types in the liver after cold preservation and transplantation. Additionally, we analyzed in vivo the patterns of functional recovery of all three cell types over the first week after transplantation in Lewis rats. METHODS: We evaluated the in vivo uptake of hyaluronic acid, indocyanine green, and radio-labeled sulphur colloid to assess the function of sinusoidal endothelial cells, hepatocytes, and Kupffer cells, respectively. Measurements were performed immediately after transplantation using syngeneic grafts preserved in University of Wisconsin solution for different periods. Functional recovery was monitored in animals receiving grafts preserved for 24 hr over the first postoperative week. RESULTS: We found that hepatocyte were less affected compared with the profoundly damaged endothelial cells. The phagocytic ability of Kupffer cells was, however, also seriously compromised, which suggests a selective down-regulation. Functional recovery occurs in a differential manner during the first postoperative week starting with hepatocytes followed by sinusoidal endothelial cells. Phagocytic function further deteriorates after transplantation before showing improvement. CONCLUSIONS: In viable liver grafts, all cell types recover from preservation/reperfusion injury by the end of the first week after transplantation. The differential time courses of the recovery suggest that successful sinusoidal endothelial cell recovery may depend upon prior hepatocyte regeneration and may involve a paracrine interaction, via cytokines and growth factors.

Alanine Transaminase↗

Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a verbal learning task.

BACKGROUND: Magnetic resonance imaging and positron emission tomography were used to study the size and metabolic rate of the caudate and the putamen in 18 patients with schizophrenia (n=16) or schizo-affective disorder (n=2) and 24 age- and sex-matched control subjects. METHODS: The patients were either never medicated (n=7) or drug free (n=11) for a median of 3 weeks. During uptake of fludeoxyglucose F 18, all patients performed a serial verbal learning test. Positron emission tomographic and magnetic resonance imaging scans were coregistered, and the caudate and the putamen were traced on the magnetic resonance image. RESULTS: The striatum had a significantly lower relative metabolic rate in schizophrenics than in controls. Never-medicated patients had lower metabolic rates in the right putamen (ventral part of the dorsal striatum) than previously medicated patients. The caudate was significantly smaller in never-medicated patients than in controls and largest in previously medicated patients. Patients with higher relative metabolic rates in the putamen scored higher on the Abnormal Involuntary Movements Scale. CONCLUSIONS: The findings are consistent with reports of striatal enlargement in previously medicated patients and size increases after neuroleptic treatment. Never-medicated patients, in contrast, had ventral striatal structures that were smaller and less active than those observed in controls and previously medicated patients.

Adolescent↗

Thallium-201 retention in focal intracranial lesions for differential diagnosis of primary lymphoma and nonmalignant lesions in AIDS patients.

UNLABELLED: The purpose of this study was to determine whether 201Tl retention in focal intracranial lesions can help distinguish central nervous system (CNS) lymphoma from toxoplasmosis and other nonmalignant CNS lesions in patients with acquired immunodeficiency syndrome. METHODS: Forty-nine patients who presented with focal lesions on CT and/or MRI had 201Tl brain SPECT studies (early and delayed image sets) performed shortly after admission. Early and delayed 201Tl uptake ratios were obtained for the positive studies, and the retention index of thallium was calculated (delayed/early target-to-background mean count ratio). RESULTS: Twenty-nine patients had foci of significantly increased 201Tl uptake on the early images in regions of corresponding CT/MRI lesions. Ten of these patients had biopsy-proven lymphomas. Another patient was found to have metastatic adenocarcinoma. Twelve additional patients had a response to radiation therapy or a clinical course consistent with lymphoma and six patients had a false-positive SPECT study. The early uptake ratio could not separate malignant from nonmalignant lesions. The 201Tl retention index in patients with lymphomas (1.18 +/- 0.16) was significantly higher than the retention index in adenocarcinoma (0.24) and in the six nonmalignant lesions (0.62 +/- 0.07). The lowest retention index in patients with lymphoma was 1.07, and the highest retention index in nonmalignant lesions was 0.70. Twenty patients showed no 201Tl uptake in the regions of CT/MRI lesions. Three of them had biopsies consistent with a benign etiology, and one patient was diagnosed with tuberculosis. Fifteen patients improved clinically on antitoxoplasmosis medications alone, and one patient had CNS lymphoma. The overall sensitivity of 201Tl brain SPECT was 96%. The specificity was 76% by counting all studies with abnormal 201Tl uptake, but it increased to 100% when the retention index was also considered. CONCLUSION: The retention index increases the specificity of 201Tl brain SPECT in human immunodeficiency virus patients. In the presence of abnormal early 201Tl uptake, it is essential to perform delayed imaging and calculate the retention index to distinguish nonmalignant lesions from lymphoma. The absence of 201Tl uptake on early images at the site of a CT/MRI abnormality excludes the diagnosis of lymphoma with a high degree of confidence and delayed imaging is unnecessary.

AIDS-Related Opportunistic Infections↗

A brain imaging (single photon emission computerized tomography) study of semantic and affective processing in psychopaths.

Psychopaths have been described as human predators who use charm, intimidation, and violence to control others and to satisfy their own needs. Underlying their propensity to violate social norms and expectations is a profound lack of empathy, guilt, or remorse, affective processes that have long resisted scientific investigation. Using brain imaging technology we found that psychopaths differed from nonpsychopaths in the pattern of relative cerebral blood flow during processing of emotional words. The results were consistent with the hypothesis that there are anomalies in the way psychopaths process semantic and affective information.

Adult↗

Non-uniform attenuation correction in SPET using a modified conjugate gradient reconstruction method.

We describe a non-uniform iterative attentuation correction method for single photon emission tomography (SPET) which uses transmission data. The method was derived using the general inverse problem theory. A cost functional which includes noise was derived and minimized using a weighted-least-square maximum a posteriori conjugate gradient (CG) method. The Hessian of the cost functional was modified by adding a noise term. The a priori value of the model data vector was neglected. The method was tested in a clinical cardiac SPET perfusion study. Prior to the emission scan, blank and transmission scans were acquired and used to obtain the non-uniform map of linear attenuation coefficients. The results of the study show that the new iterative method has a slightly better convergence rate than the standard CG method. Also, the corrected emission slices obtained by the new method were less noisy. Noise was measured as rms% and was reduced by a factor of 2.3 for the transmission scans and by a factor of 1.9 for the emission scans when reconstructed with the new method compared to the CG method. The new method provides a stable solution, whereas the standard CG method, for higher iterative steps, diverges. There is potential for improvement in the approach described here.

Humans↗

Enhanced cross-talk correction technique for simultaneous dual-isotope imaging: a TL-201/Tc-99m myocardial perfusion SPECT dog study.

A newly developed cross-talk correction method for simultaneous dual-isotope SPECT imaging was tested in a canine model. The method is based on the assumption that the transformations, which modify the primary energy window images into the scatter images as viewed in the other energy windows, are known. These transformations were found by measuring the point spread functions (PSFs) in two different energy windows for both isotopes in water. The dual-isotope correction method is described by two convolution equations which were applied in frequency space. The equations take into account the different spatial distributions of the primary and scatter cross-talk photons. The new enhancement of the method was in applying restoration filters to the resulting corrected images. Three separate studies were acquired in our dog study: two single-isotope and one dual-isotope study. The single isotope images were used as references. The contrast between the left ventricle cavity (LVC) and the myocardium was used in transaxial and short-axis slices as a parameter to evaluate results of dual-isotope correction method with restoration. The change in contrast in the dual-isotope corrected images in both energy windows, i.e., Tc-99m primary window (140 keV) and Tl-201 primary window (70 keV), was significant. The only exception was for the short-axis Tc-99m window images. The corrected 140 keV dual-isotope short-axis slice had the contrast of 0.60 vs 0.58, which was the value in the noncorrected dual-isotope short-axis slice. For dual-isotope 140 keV transaxial slice, the contrast changed from 0.72 to 0.82 after correction. In comparison, for single-isotope Tc-99m 140 keV transaxial slice, contrast changed from 0.62 to 0.84 after restoration correction. There was less change in contrast in the short-axis Tc-99m 140 keV slice, i.e., from 0.56 to 0.61. In the Tl-201 primary window for the transaxial slices the improvement of contrast was from 0.38 to 0.64, and for short-axis slices from 0.22 to 0.32 after correction. In the same 70 keV energy window for single-isotope Tl-201 images, contrast improved from 0.61 to 0.69 and from 0.35 to 0.38 for transaxial and short-axis slice, respectively, after applying restoration correction. In conclusion, the presented dual-isotope correction method with restoration improves the quality of the simultaneous rest Tl-201/stress Tc-99m sestamibi SPECT imaging.

Animals↗

Pre-clinical evaluation of technetium-99m platelet receptor-binding peptide.

UNLABELLED: P748 is a dimeric peptide which incorporates two high affinity GPIIb/IIIa receptor-binding domains and a novel 99mTc binding sequence, which provides the platelet imaging agent 99mTc-P748. The aim of this study was to evaluate 99mTc-P748 preclinically for use as a hot spot scintigraphic thrombus imaging agent. METHODS: Technetium-99m-P748 was prepared by either a ligand exchange or a one-vial kit. The oxorhenium congener, [ReO]P748, was prepared by ligand exchange from Bu4NReOBr4. The binding of P748 peptide and [ReO]P748 to GPIIb/IIIa receptors on activated platelets was assessed by their inhibition of ADP stimulated human platelet aggregation in platelet rich plasma (PRP). The localization of 99mTc-P748 in deep vein and pulmonary thrombi was assessed in a canine thrombosis model and the biodistribution of 99mTc-P748 was determined in rats. RESULTS: P748 peptide inhibited the aggregation of human platelets in PRP by 50% at a concentration (IC50) of 28 nM and [ReO]P748 had an IC50 of 36 nM showing the high in vitro receptor binding affinity of both the peptide and its rhenium complex (and by analogy its technetium complex). Technetium-99m-P748 was readily prepared at room temperature in 15 min in > or = 90% radiochemical yield and purity and provided definitive images of femoral vein thrombi within 20 min and pulmonary thrombi, within 1 hr in the canine model. Femoral vein thrombus-to-blood and thrombus-to-muscle ratios at 4 hr averaged 6.7 and 46, respectively. Pulmonary thrombus-to-blood and thrombus-to-normal lung ratios at 4 hr averaged 29 and 27, respectively. Dog and rat studies both showed rapid clearance of the radiotracer from the blood and with no significant hepatobiliary excretion but with notable early kidney retention. CONCLUSION: The combination of high in vitro receptor-binding affinity, high thrombus uptake and definitive in vivo images of both femoral vein and pulmonary thrombi show that 99mTc-P748 has considerable potential as a clinical imaging agent for the detection of venous thromboembolism.

Animals↗

Effect of haloperidol dose on iodine-123-IBZM brain SPECT imaging in schizophrenic patients.

UNLABELLED: Studies have suggested that antipsychotic drug therapy with haloperidol in schizophrenic patients requires an optimal dose that blocks the brain dopamine D2 receptors. We evaluated the effect of different doses of haloperidol on D2 receptor occupancy in schizophrenia. METHODS: Three normal subjects and three patients with acute schizophrenia had serial brain SPECT imaging studies (every 5 min) for 3 hr following the injection of [123I]IBZM. The patients had IBZM studies off medication and at different doses (1-10 mg) of haloperidol. RESULTS: The basal ganglia (BG) were well visualized in normals and in schizophrenics off medication. After haloperidol therapy, SPECT images showed qualitatively diminished activity in the basal ganglia. ROIs were drawn over the basal ganglia and cerebellum (CE). The results were expressed as BG/CE ratios. At 2 hr postinjection of IBZM, the mean BG/CE ratio in normals was 1.75 +/- 0.025. In schizophrenics, the BG/CE ratio off medication was 1.54 +/- 0.12. The BC/CE ratio showed an inverse relationship to haloperidol dose; 1.46 at 1 mg, 1.25 at 4 mg and 1.05 at 10 mg, respectively. CONCLUSION: These results demonstrate that IBZM brain SPECT imaging studies are potentially useful to relate the antipsychotic drug D2 receptor occupancy with the administered dose in schizophrenic patients and may ultimately help optimize antipsychotic treatment.

Adult↗

The role of thallium-201 uptake and retention in intracranial tumors after radiotherapy.

UNLABELLED: This study prospectively assessed the diagnostic accuracy and prognostic value of 201TI uptake and retention in primary and metastatic intracranial tumors treated by conventional radiotherapy and/or radiosurgery. METHODS: An initial 201TI study (early and delayed images), was obtained in 60 postsurgical patients, 6-12 wk after radiotherapy or radiosurgery. Repeat imaging was performed as clinically warranted. Tumor-to-background count ratios and a retention index (RI) were calculated for all lesions. RESULTS: Abnormally increased 201TI uptake was observed in 40 of 60 patients. In all patients with positive results, the diagnosis of residual tumor was confirmed at biopsy or by clinical follow-up. In 20 of 60 patients, no abnormal 201TI uptake was observed, despite findings on CT and/or MRI scans that were suspicious for tumor. Ten of the negative 201TI studies were confirmed as true-negatives by the clinical course and by resolution of CT/MRI abnormalities. The remaining 10 negative SPECT studies ultimately proved to be false-negatives: six of these patients had lesions < 1 cm in maximum diameter, one patient had a large metastatic choriocarcinoma; and three patients had low-grade astrocytomas > 2 cm in minimum diameter. Tumor-to-background ratio of 201TI uptake did not distinguish between tumor type, or predict clinical outcome. The RI of 201TI was significantly higher for metastatic melanoma than for other tumor metastases. It demonstrated reasonably good correlation with clinical outcome: 6/7 patients with eventual tumor regression showed a decrease in RI on follow-up examination, and 4/5 patients with eventual tumor progression had an increase in RI. CONCLUSION: Thallium-201 brain SPECT appears to be a useful noninvasive imaging technique in patients irradiated for intracranial tumors. Thallium-201 scintigraphy has very high specificity (100% in this cohort) for detecting viable residual tumor. False-negative findings may occur. Quantitative analysis of 201TI uptake has limited diagnostic and prognostic significance, but changes in 201TI retention after radiation therapy seems to have prognostic value.

Adolescent↗

Scintigraphic monitoring of reticuloendothelial system in patients with type 1 Gaucher disease on enzyme replacement therapy.

UNLABELLED: The purpose of this study was to define the scintigraphic pattern of marrow replacement and changes in reticuloendothelial activity after enzyme replacement therapy in patients with Gaucher disease. METHODS: Forty patients underwent baseline whole-body imaging with 99mTc-sulfur colloid and evaluation of liver and spleen volume with CT or magnetic resonance imaging. Thirty-seven of the 40 patients were treated with enzyme replacement. Therapeutic responses of central and peripheral bone marrow and the changes in pulmonary uptake of 99mTc-sulfur colloid were assessed visually at 1-4 yr after the start of therapy. Changes in liver and spleen volumes were analyzed quantitatively. The initial pattern of marrow involvement was correlated with disease severity (based on baseline blood counts and liver and spleen volumes). RESULTS: Baseline studies revealed that 38 of 40 (95%) and 28 of 40 (70%) of the patients in this study had abnormal peripheral and central marrow activity, respectively. Twenty of 24 evaluable patients (83.3%) on therapy showed regression of peripheral bone marrow activity to a more proximal location in the lower extremities, increased ratio of pelvic/proximal femoral activity to distal activity or both. Fourteen of 19 treated patients (73.7%) with abnormal initial central marrow activity showed detectable improvement in central bone marrow activity as a result of therapy. In patients with initial lung uptake of 99mTc-sulfur colloid, 91% showed complete resolution of the uptake after therapy. These changes in colloid uptake and distribution were associated with significant reductions in liver and spleen volumes and improvements in blood counts. CONCLUSION: Most patients with Gaucher disease demonstrate increased central bone marrow activity and regression of activity in peripheral bone marrow with enzyme replacement therapy. Additionally, the abnormal phagocytic pulmonary activity observed before therapy in many of the patients resolves.

Adult↗

Preclinical studies of indium-111-labeled IgM: a human monoclonal antibody for infection imaging.

UNLABELLED: Indium-111-labeled plasma proteins, such as albumin, transferrin and IgG, have been proven useful to image infection. We reported previously that 111In-labeled human monoclonal antibody, IgM 16.88 (In-IgM) also would localize at the site of infection. However, the kinetics of blood clearance, distribution and infection uptake have not been investigated. We compared the kinetics of distribution and infection uptake of In-IgM 16.88 with that of in-polyclonal IgG in rats with focal infection. METHODS: Both IgM 16.88 and polyclonal IgG were labeled with 111In using a bifunctional chelating agent, LiLo. The labeling efficiency was > 95%. Focal infection was induced in rats by an intramuscular injection of E. Coli in the right thigh. In-IgM (30-40 microCi) was injected into five groups of rats (five rats/group). The rats were killed at 4, 8, 16, 24 and 36 hr. The percent injected dose (%ID) in blood, infection muscle, control muscle, liver, spleen and kidney were determined. Similar studies were performed with In-IgG. RESULTS: The In-IgM activity in blood at 4 hr postinjection was 27% which decreased to 2% by 36 hr. In contrast, the In-IgG blood activity was 40% at 4 hr and 20% at 36 hr. The infection/ muscle (I/M) ratios are higher with In-IgM at all time points postinjection compared to that of In-IgG. At 24 hr, the I/M ratio was 22 compared to 9 with In-IgG. At the same time point, the infection/ blood (I/B) ratio with In-IgM was 2.7 compared to only 0.8 with that of In-IgG. In-IgM was taken up mostly by the liver compared to diffuse abdominal uptake of IgG. CONCLUSION: These result indicate that In-IgM produces higher lesion to background ratio when compared to In-IgG and, therefore, is potentially useful to image infection in patients.

Animals↗

Adrenal glands imaging with indium-111-DTPA-D-Phe1-octreotide following ACTH therapy.

Somatostatin receptors have been identified in a variety of neuroendocrine tumors and activated leukocytes. A high density of somatostatin receptors is also present in most intestinal intramural veins of patients with inflammatory bowel disease. We present a case of a 25-yr-old female with severe Crohn's disease unresponsive to medical therapy, including adrenocorticotropic hormone (ACTH) administration. The patient underwent (111)In-DTPA octreotide scintigraphy to evaluate the potential role of somatostatin receptor imaging in inflammatory bowel disease. Despite the lack of significant somatostatin receptors in the affected bowel, an unexpected prominent activity of (111)In-DTPA octreotide was noted in the adrenal glands on the SPECT images, presumably resulting from excessive stimulation by ACTH. The expression of somatostatin receptors in the stimulated adrenals may be used to image other adrenal pathologies and could potentially indicate response to therapy.

Adrenal Glands↗