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Biomedical subjects

R Edward Coleman

Publications and source records attributed to R Edward Coleman.

At least 19 recordsLinked to original sources
PubMed2007

Cell therapy in murine atherosclerosis: in vivo imaging with high-resolution helical SPECT.

PURPOSE: To determine the feasibility of in vivo localization and quantification of indium 111 (111In)-oxine-labeled bone marrow (BM) with high-resolution whole-body helical single photon emission computed tomography (SPECT) in an established murine model of atherosclerosis and vascular repair. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. BM from young B6 Rosa 26 Lac Z+/+ mice was radiolabeled with 111In-oxine. On days 1, 4, and 7 after administration of radiolabeled cells, five C57/BL6 apolipoprotein E-deficient mice and five wild-type (WT) control mice were imaged with whole-body high-resolution helical SPECT. Quantification with SPECT was compared with ex vivo analysis by means of gamma counting. Autoradiography and beta-galactosidase staining were used to verify donor cell biodistribution. Linear regression was used to assess the correlation between continuous variables. Two-tailed Student t test was used to compare values between groups, and paired two-tailed t test was used to assess changes within subjects at different time points. RESULTS: SPECT image contrast was high, with clear visualization of BM, liver, and spleen 7 days after administration of radiolabeled cells. SPECT revealed that 42% and 58% more activity was localized to the aorta and BM (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. Furthermore, 28% and 27% less activity was localized to the liver and spleen (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. SPECT and organ gamma counts showed good quantitative correlation (r=0.9). beta-Galactosidase staining and microautoradiography of recipient aortas showed donor cell localization to the intima of visible atherosclerotic plaque but not to unaffected regions of the vessel wall. CONCLUSION: High-resolution in vivo helical pinhole SPECT can be used to monitor and quantify early biodistribution of 111In-oxine-labeled BM in a murine model of progenitor cell therapy for atherosclerosis.

Animals↗
PubMed2006

Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy. RESULTS: With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks, respectively. Ten patients (23%) developed acute hematologic toxicity. Five patients (12%) developed acute reversible neurotoxicity. One patient (2%) developed irreversible neurotoxicity. No patients required reoperation for radionecrosis. CONCLUSION: In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.

Adult↗
PubMed2006

Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma.

PURPOSE: We performed a retrospective study of patients with diffuse pontine glioma (DPG) who suffered neuraxis metastasis (NM) and characterized the incidence, clinical features, radiologic findings, and patterns of disease dissemination. METHODS: Magnetic resonance imaging (MRI) of brain and spine was used to assess NM. Some patients also underwent magnetic resonance spectroscopy (MRS) (6 patients) and fluorodeoxyglucose positron emission tomography (FDG-PET) scans (13 patients) to further evaluate areas of metastatic disease. Three patients had histologic confirmation of disease at the site of NM. RESULTS: Between 1986 and 2003, 18 of 96 patients (17.3%) with DPG developed NM. The median age at diagnosis was 8 years (range, 4-17). All patients had adjuvant chemotherapy and/or focal radiotherapy at diagnosis. The NM occurred at a median of 15 months from diagnosis of DPG (range, 3-96). Three patterns of NM were seen on MRI of brain and spine in these patients; 8 (39%) had parenchymal (PM), 4 (22%) leptomeningeal (PM), 2 (11%) subependymal, and in 5 a combination of two or more patterns. The MRS and FDG-PET scan of suspected areas of metastatic disease was consistent with tumor in 6 of 6 and 12 of 13 patients who underwent these procedures respectively. Three patients also had histologic confirmation of malignant glioma at the site of NM. Despite salvage therapy, all 18 patients have died of disease at a median of 5 months (range, 0.5-20) from diagnosis of neuraxis spread. CONCLUSION: Our study emphasizes the need for screening patients with DPG for NM at the time of recurrence.

Adolescent↗
PubMed2006

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. METHODS: In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). (131)I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after (131)I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. RESULTS: We treated 47 patients with (131)I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. CONCLUSION: The MTD of (131)I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, (131)I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with (131)I-murine 81C6.

Adult↗
PubMed2005

Changes in plasma volume associated with mental stress ischemia in patients with coronary artery disease.

Psychological stress has been shown to trigger angina and myocardial ischemia in patients with coronary artery disease. However, the mechanisms by which stress may trigger cardiac events has yet to be fully elucidated. Twenty five patients underwent radionuclide ventriculography during a multiple stress challenge. Plasma volume was assessed during rest and at the end of the stress task. Flow-mediated dilatation was also measured. Controlling for endothelial function and medications, patients with ischemia had greater reductions in plasma volume than non-ischemic patients. Reduced plasma volume may be one mechanism by which mental stress may increase the risk for acute coronary events.

Aged↗
PubMed2005

Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial.

CONTEXT: Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality, but the effects of behavioral interventions on psychosocial and medical end points remain uncertain. OBJECTIVE: To determine the effect of 2 behavioral programs, aerobic exercise training and stress management training, with routine medical care on psychosocial functioning and markers of cardiovascular risk. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of 134 patients (92 male and 42 female; aged 40-84 years) with stable ischemic heart disease (IHD) and exercise-induced myocardial ischemia. Conducted from January 1999 to February 2003. INTERVENTIONS: Routine medical care (usual care); usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks; usual care plus weekly 1.5-hour stress management training for 16 weeks. MAIN OUTCOME MEASURES: Self-reported measures of general distress (General Health Questionnaire [GHQ]) and depression (Beck Depression Inventory [BDI]); left ventricular ejection fraction (LVEF) and wall motion abnormalities (WMA); flow-mediated dilation; and cardiac autonomic control (heart rate variability during deep breathing and baroreflex sensitivity). RESULTS: Patients in the exercise and stress management groups had lower mean (SE) BDI scores (exercise: 8.2 [0.6]; stress management: 8.2 [0.6]) vs usual care (10.1 [0.6]; P = .02); reduced distress by GHQ scores (exercise: 56.3 [0.9]; stress management: 56.8 [0.9]) vs usual care (53.6 [0.9]; P = .02); and smaller reductions in LVEF during mental stress testing (exercise: -0.54% [0.44%]; stress management: -0.34% [0.45%]) vs usual care (-1.69% [0.46%]; P = .03). Exercise and stress management were associated with lower mean (SE) WMA rating scores (exercise: 0.20 [0.07]; stress management: 0.10 [0.07]) in a subset of patients with significant stress-induced WMA at baseline vs usual care (0.36 [0.07]; P = .02). Patients in the exercise and stress management groups had greater mean (SE) improvements in flow-mediated dilation (exercise: mean [SD], 5.6% [0.45%]; stress management: 5.2% [0.47%]) vs usual care patients (4.1% [0.48%]; P = .03). In a subgroup, those receiving stress management showed improved mean (SE) baroreflex sensitivity (8.2 [0.8] ms/mm Hg) vs usual care (5.1 [0.9] ms/mm Hg; P = .02) and significant increases in heart rate variability (193.7 [19.6] ms) vs usual care (132.1 [21.5] ms; P = .04). CONCLUSION: For patients with stable IHD, exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone.

Adult↗
PubMed2005

Incremental prognostic power of single-photon emission computed tomographic myocardial perfusion imaging in patients with known or suspected coronary artery disease.

Noninvasive stress testing provides prognostic information in patients who have suspected coronary artery disease, but limited data are available on the incremental value of myocardial perfusion testing in high-risk patients. We studied 3,275 patients who underwent cardiac catheterization and single-photon emission computed tomographic (SPECT) perfusion imaging. Median follow-up was 3.1 years for death, cardiovascular death, and a composite of cardiovascular death or nonfatal myocardial infarction. Using Cox's proportional hazards regression models, we examined the relation of SPECT summed stress score (SSS) to each outcome. A 1-unit change in SSS was associated with increased risks of 4%, 7%, and 5% for death, cardiovascular death, and death or nonfatal myocardial infarction, respectively (all p <0.0001). To examine the prognostic utility of SPECT, after baseline adjustments, SSS and angiographic results provided incremental prognostic information for each outcome. Thus, SPECT SSS provides information beyond clinical and angiographic data in patients who have known or suspected coronary artery disease. This information may be useful for stratifying patients into multiple risk categories for future cardiovascular events and potentially guiding therapy.

Aged↗
PubMed2005

Positron emission tomography diagnosis of Alzheimer's disease.

Positron emission tomography (PET) imaging of [18F]-2-fluoro-2-deoxy-D-glucose (FDG) is accurate in the early detection of Alzheimer's disease (AD) and in the differentiation of AD from the other causes of dementia. FDG-PET imaging is available widely and performed easily. Different patterns of abnormality with the various causes of dementia are well described. Semiquantitative methods of image interpretation are available. Medicare covers FDG-PET imaging for the narrow indication of differentiation of possible AD from frontotemporal dementia.

Alzheimer Disease↗
PubMed2005

Detection of primary breast carcinoma with a dedicated, large-field-of-view FDG PET mammography device: initial experience.

PURPOSE: To prospectively assess a dedicated, large field of view positron emission tomography (PET) mammographic device for imaging primary breast carcinoma. MATERIALS AND METHODS: Institutional review board approval was obtained for this study, and all patients provided written informed consent prior to participation. Subjects were recruited from a cohort of patients in whom diagnostic mammography and/or ultrasonography demonstrated lesions that were highly suggestive of malignancy. Twenty-three patients who met the inclusion criteria were subsequently imaged by using a dedicated PET mammography unit that was developed in conjunction with the Thomas Jefferson National Accelerator Facility (Newport News, Va). One hour after administration of 2.0-2.5 mCi (74.0-93.5 MBq) of fluorodeoxyglucose, 5-minute PET mammography of the affected breast was performed. Images were processed and reconstructed in the transverse craniocaudal and coronal planes. For each lesion, image-guided core-needle biopsy was performed immediately after PET mammography. Conventional mammography results and histologic findings were correlated with PET mammography images. The sensitivity, specificity, negative predictive value, and positive predictive value of PET mammography for demonstrating malignant lesions were calculated. RESULTS: PET mammography demonstrated 20 focal abnormalities, of which 18 were malignant and two were benign. Both benign lesions represented areas of fat necrosis. Three of 20 malignant lesions demonstrated at conventional mammography were not demonstrated at PET mammography. The overall sensitivity of PET mammography for malignancy was 86% (95% confidence interval: 65%, 95%), with a positive predictive value of 90% (95% confidence interval: 70%, 97%). The calculated specificity was 33% (95% confidence interval: 2%, 79%), and the negative predictive value was 25% (95% confidence interval: 1%, 70%). CONCLUSION: These pilot data suggest that PET mammography can demonstrate small primary breast malignancies.

Adenocarcinoma↗
PubMed2005

Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study.

Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to transforming growth factor (TGF)-alpha. TGF-alpha binds with high affinity to the epidermal growth factor receptor, which is uniformly overexpressed in malignant gliomas, often because of gene amplification. Prior to therapy with TP-38, the patient described here was completely refractory to multiple other therapies, with radiographic and pathologic evidence of tumor progression. After therapy, she improved clinically, was weaned off steroids and anti-convulsants, and experienced a progressive decrease in enhancing tumor volume. Despite multiple prior recurrences, she has not progressed for >43 months after TP-38 therapy. Small remaining areas of enhancement demonstrate no evidence of tumor histologically and are hypometabolic on positron emission tomography. This report describes a dramatic and sustained clinical and radiographic response in a patient with a bifrontal glioblastoma multiforme treated with intratumoral infusion of a novel targeted toxin, TP-38.

Brain Neoplasms↗
PubMed2005

Prediction of death and nonfatal myocardial infarction in high-risk patients: a comparison between the Duke treadmill score, peak exercise radionuclide angiography, and SPECT perfusion imaging.

UNLABELLED: Radionuclide exercise testing provides prognostic information in patients with known or suspected coronary artery disease (CAD). The relative contribution of 3 noninvasive tests--the Duke treadmill score (DTS), first-pass radionuclide angiography with calculation of the ejection fraction (RNA-EF), and perfusion SPECT--has not been comparatively assessed in a high-risk population undergoing all 3 tests. METHODS: We identified 997 patients (75% male; median age, 60 y) who underwent exercise treadmill testing with RNA-EF and SPECT perfusion imaging as a single test. The relative prognostic power of each test was evaluated in both an unadjusted manner and after adjustment for differences in baseline characteristics using Cox proportional hazards models. RESULTS: During a median follow-up of 4.1 y, 175 patients experienced outcome events. Without adjustment for baseline patient characteristics, each of the modalities proved highly predictive of the composite endpoint of cardiovascular death or nonfatal myocardial infarction (MI) (DTS chi(2) = 18.9, P = 0.0001; RNA-EF chi(2) = 34, P = 0.0001; SPECT chi(2) = 11.5, P = 0.0007). In clinically risk-adjusted models, RNA-EF was the most powerful predictor of cardiovascular death compared with the DTS and SPECT (chi(2) = 40.5, 27.6, and 19.8, respectively). Conversely, exercise SPECT perfusion was a stronger predictor of nonfatal MI than the DTS or RNA-EF (chi(2) = 26.7, 15.7, and 16.7, respectively). CONCLUSION: The DTS, perfusion SPECT, and RNA-EF are each significant predictors of cardiovascular events in high-risk patients. The optimal risk stratification of patients for CAD may include all 3 modalities.

Exercise Test↗
PubMed2005

Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.

UNLABELLED: The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy. METHODS: Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients. RESULTS: This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival. CONCLUSION: This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

Adult↗
PubMed2005

Concurrent PET/CT with an integrated imaging system: intersociety dialogue from the joint working group of the American College of Radiology, the Society of Nuclear Medicine, and the Society of Computed Body Tomography and Magnetic Resonance.

Rapid advances in imaging technology are a challenge for health care professionals, who must determine how best to use these technologies to optimize patient care and outcomes. Hybrid imaging instrumentation, combining 2 or more new or existing technologies, each with its own separate history of clinical evolution, such as PET and CT, may be especially challenging. CT and PET provide complementary anatomic information and molecular information, respectively, with PET giving specificity to anatomic findings and CT offering precise localization of metabolic activity. Historically, the acquisition and interpretation of the 2 image sets have been performed separately and very often at different times and locales. Recently, integrated PET/CT systems have become available; these systems provide PET and CT images that are acquired nearly simultaneously and are capable of producing superimposed, coregistered images, greatly facilitating interpretation. As the implementation of this integrated technology has become more widespread in the setting of oncologic imaging, questions and concerns regarding equipment specifications, image acquisition protocols, supervision, interpretation, professional qualifications, and safety have arisen. This article summarizes the discussions and observations surrounding these issues by a collaborative working group consisting of representatives from the American College of Radiology, the Society of Nuclear Medicine, and the Society of Computed Body Tomography and Magnetic Resonance.

Humans↗
PubMed2004

Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients.

BACKGROUND: Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging carcinoid tumors and recently has been applied to the palliative treatment of metastatic carcinoid in small studies. The authors now report their results on the therapeutic utility of high-dose 131I-MIBG treatment in a large group of patients with metastatic carcinoid tumors. METHODS: The authors performed a retrospective review of 98 patients with metastatic carcinoid who were treated at their institution with 131I-MIBG over a 15-year period. Endpoints examined included the World Health Organization criteria for treatment response: symptoms, hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor response. RESULTS: Patients received a median dose of 401 +/- 202 millicuries (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who experienced a symptomatic response had improved survival (5.76 years vs. 2.09 years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/- 122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5-HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P = 0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05). Radiographic tumor response did not predict survival. Toxicity included pancytopenia, thrombocytopenia, nausea, and emesis. CONCLUSIONS: The current data support 131I-MIBG treatment in select patients with metastatic carcinoid who progress despite optimal medical management. Improved survival was predicted best by symptomatic response to 131I-MIBG treatment, but not by hormone or radiographic response.

3-Iodobenzylguanidine↗