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ABSTRACT: PURPOSE: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. METHODS: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. RESULTS: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). CONCLUSION: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.
CardioVascular and Interventional Radiology 01/2013; · 2.09 Impact Factor
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European journal of nuclear medicine and molecular imaging 04/2012; 35(9):1746-1746. · 4.99 Impact Factor
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ABSTRACT: IntroductionThe American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy
has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar®,
a 131I radiolabeled murine monoclonal antibody and Zevalin®, a 90Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical
experience with Bexxar® and Zevalin® in the management of low-grade refractory or relapsed NHL.
MethodsThis is a retrospective study (Jan 2000–Jul 2006) of 67 patients with NHL, who were treated with Bexxar® (31 patients, group
A) or Zevalin® (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35–81years old
(average, 59.3 ± 13.4). Group B included 27 men and nine women, 36–85years old (average, 55.4 ± 13.8). Therapeutic doses
ranged 40–138mCi (average, 78.1 ± 28.2) for Bexxar® and 17–34mCi (average, 28.8 ± 4.37) for Zevalin®.
ResultsObjective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B.
Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four
patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression
in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed
response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients
(11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9% ± 0.33 (group A)
and 52.6% ± 0.32 (group B) for platelets, 27.8% ± 0.27 (group A) and 34.2% ± 0.38 (group B) for leukocytes, and 4.9% ± 0.15
(group A) and 7.6% ± 0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%)
treated with Bexxar® and 22 patients (61.1%) treated with Zevalin®, but was reversible.
ConclusionOur study suggests that clinical practice of Bexxar® and Zevalin® radioimmunotherapy is an effective and safe adjunctive treatment
for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was
not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.
Key wordsBexxar-Zevalin-Therapy-Non-Hodgkin-Lymphoma
Molecular Imaging & Biology 04/2012; 12(2):198-203. · 3.84 Impact Factor
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ABSTRACT: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.
(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.
PETRIT was obtained with a specific activity of 545 ± 38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean ± STD) with and without pre-dose was 1.76 ± 0.43% and 16.5 ± 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 ± 0.51% and 0.52 ± 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 ± 0.4 μSv/MBq and the spleen at 99 ± 4 μSv/MBq, respectively.
PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 01/2012; 14(5):608-16. · 2.47 Impact Factor
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Erik S Mittra, Michael L Goris,
Andrei H Iagaru,
Arash Kardan,
Lindee Burton,
Rhona Berganos,
Edwin Chang,
Shuanglong Liu,
Bin Shen,
Frederick T Chin,
Xiaoyuan Chen,
Sanjiv S Gambhir
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ABSTRACT: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets α(v)β(3) integrin, in the first volunteers imaged with this tracer.
The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/mmol ± 714 [44.4 GBq/mmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests.
The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of (18)F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096).
(18)F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.
Radiology 07/2011; 260(1):182-91. · 5.73 Impact Factor
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Journal of Nuclear Medicine 12/2009; · 6.38 Impact Factor
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Journal of Nuclear Medicine 06/2009; · 6.38 Impact Factor
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ABSTRACT: (18)F-FDG PET/CT is used for detecting cancer and monitoring cancer response to therapy. However, because of the variable rates of glucose metabolism, not all cancers are identified reliably. Sodium (18)F was previously used for bone imaging and can be used as a PET/CT skeletal tracer. The combined administration of (18)F and (18)F-FDG in a single PET/CT study for cancer detection has not been reported to date.
This is a prospective pilot study (November 2007-November 2008) of 14 patients with proven malignancy (6 sarcoma, 3 prostate cancer, 2 breast cancer, 1 colon cancer, 1 lung cancer, and 1 malignant paraganglioma) who underwent separate (18)F PET/CT and (18)F-FDG PET/CT and combined (18)F/(18)F-FDG PET/CT scans for the evaluation of malignancy (a total of 3 scans each). There were 11 men and 3 women (age range, 19-75 y; average, 50.4 y).
Interpretation of the combined (18)F/(18)F-FDG PET/CT scans compared favorably with that of the (18)F-FDG PET/CT (no lesions missed) and the (18)F PET/CT scans (only 1 skull lesion seen on an (18)F PET/CT scan was missed on the corresponding combined scan). Through image processing, the combined (18)F/(18)F-FDG scan yielded results for bone radiotracer uptake comparable to those of the (18)F PET/CT scan performed separately.
Our pilot-phase prospective trial demonstrates that the combined (18)F/(18)F-FDG administration followed by a single PET/CT scan is feasible for cancer detection. This combined method opens the possibility for improved patient care and reduction in health care costs.
Journal of Nuclear Medicine 05/2009; 50(4):501-5. · 6.38 Impact Factor
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ABSTRACT: To prepare for yttrium-90 ((90)Y) microsphere radioembolization therapy, digital subtraction angiography (DSA) and technetium- 99m-labeled macroaggregated albumin ((99m)Tc MAA) scintigraphy are used for treatment planning and detection of potential nontarget embolization. The present study was performed to determine if cone-beam computed tomography (CBCT) affects treatment planning as an adjunct to these conventional imaging modalities.
From March 2007 to August 2008, 42 consecutive patients (21 men, 21 women; mean age, 59 years; range, 21-75 y) who underwent radioembolization were evaluated by CBCT in addition to DSA and (99m)Tc MAA scintigraphy during treatment planning, and their records were retrospectively reviewed. The contrast-enhanced territories shown by CBCT with selective intraarterial contrast agent administration were used to predict intrahepatic and possible extrahepatic distribution of microspheres.
In 22 of 42 cases (52%), extrahepatic enhancement or incomplete tumor perfusion seen on CBCT affected the treatment plan. In 14 patients (33%), the findings were evident exclusively on CBCT and not detected by DSA. When comparing CBCT versus (99m)Tc MAA scintigraphy, CBCT showed eight cases of extrahepatic enhancement (19%) that were not evident on (99m)Tc MAA imaging. CBCT findings directed the additional embolization of vessels or repositioning of the catheter for better contrast agent and microsphere distribution. One case of gastric ulcer from nontarget embolization caused by reader error was observed.
CBCT can provide additional information about tumor and tissue perfusion not currently detectable by DSA or (99m)Tc MAA imaging, which should optimize (90)Y microsphere delivery and reduce nontarget embolization.
Journal of vascular and interventional radiology: JVIR 05/2009; 20(5):606-13. · 1.81 Impact Factor
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ABSTRACT: Autoimmune pulmonary alveolar proteinosis (APAP) is characterized by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood and tissues, resulting in alveolar surfactant protein accumulation. Patients with APAP present with ground-glass opacities (GGOs) and interlobular septal thickening on thin-slice chest CT scans. Aerosolized GM-CSF therapy (aeroGM-SCF) has qualitatively improved the clinical condition of patients with APAP. This report details quantitative chest CT responses to aeroGM-CSF.
Two adolescent patients (aged 16 and 19 years) with APAP were treated with aeroGM-CSF. Clinical parameters, including pulmonary function tests and chest CT scans, were obtained before and after aeroGM-CSF therapy. To evaluate the effect of the therapy, serial chest CT scans were analyzed using a novel approach permitting quantitative assessment of improvement in GGOs, lung weight, and gas volume.
In association with GM-CSF treatment, nutritional status and pulmonary function improved. Quantitative analysis of the CT scans demonstrated reduction in GGOs and lung weight, concomitant with an increase in airspace volume and lung inflation. The findings were consistent with a qualitative reduction in GGOs on chest CT imaging.
Quantitative analysis of CT holds promise as a sensitive diagnostic tool permitting longitudinal and objective analysis of the therapeutic response to aeroGM-CSF in patients with APAP.
Chest 04/2009; 135(3):842-8. · 5.25 Impact Factor
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ABSTRACT: Radioimmunotherapy is an effective treatment for non-Hodgkin's lymphoma (NHL). 90Y-ibritumomab is an antibody targeting CD20 receptors on the surface of lymphocytes. We present observations from our clinical experience with 90Y-ibritumomab in the management of NHL.
This was a retrospective study of 28 NHL patients treated with 90Y-ibritumomab. There were 21 men and 7 women, 36-85 y old. A diagnostic dose of 111In-ibritumomab was administered on day 0, and imaging followed immediately and at 24, 48, and 72 h. The doses of 90Y-ibritumomab ranged from 629 to 1,258 MBq (17-34 mCi). Outcomes were compared with the findings of the 111In-ibritumomab scans.
90Y-ibritumomab induced objective responses in 22 of 28 patients. A complete response was noted in 9 patients, a partial response in 9 patients, and a mixed response in 4 patients. Three patients had stable disease, and 3 patients had disease progression. 111In-ibritumomab findings were positive in 19 patients and negative in 9 patients. A complete response was noted in 2 of 19 patients with positive findings and 7 of 9 with negative findings. A partial response was seen in 7 of 19 patients with positive findings and 1 of 9 with negative findings. Disease progression was observed in 3 of 19 patients with positive findings and 0 of 9 with negative findings. The remaining patients had a mixed response or no changes.
A higher rate of complete response after 90Y-ibritumomab treatment was seen in patients with negative 111In-ibritumomab findings, whereas a higher rate of disease progression despite therapy was noted in patients with positive 111In-ibritumomab findings. This observation suggests that patients with bulky disease may require more aggressive management.
Journal of Nuclear Medicine 11/2008; 49(11):1809-12. · 6.38 Impact Factor
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European journal of nuclear medicine and molecular imaging 09/2008; 35(9):1746. · 4.99 Impact Factor
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ABSTRACT: Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on accurate staging and prognostic estimations, as well as evaluation of response to therapy as early after initiation as possible. We focus on several aspects of molecular imaging and therapy that affect the management of patients who have lymphoma. First, we review prior use of gallium-67 citrate for evaluation of lymphoma patients, mainly from a historical perspective, since it was the mainstream lymphoma functional imaging tracer for decades. Next, we review current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma. Finally, we discuss advances in molecular imaging that may herald the next generation of PET radiotracers after 18F FDG.
Radiologic Clinics of North America 04/2008; 46(2):243-52, viii. · 2.59 Impact Factor
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ABSTRACT: Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy.
CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation.
(99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d.
We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.
Journal of Nuclear Medicine 12/2007; 48(11):1822-8. · 6.38 Impact Factor
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ABSTRACT: Medical imaging has increasingly provided surrogate endpoints in therapeutic trials. This use assumes that the interpretation of the images can be unbiased and reproducible and that the image attributes included in the interpretation are relevant to the mechanism of the trial. The principal motivation for computer analysis is to evaluate an attribute of the image as a metric in an algorithmic manner, independent of observer bias or variability. The metric is expected to reflect change in rough proportion with at least one aspect of the degree of disease or the effectiveness of the therapeutic intervention. If either condition is satisfied, the measure is quantitative. Visual interpretation explicitly or implicitly tends to be based on multiple image attributes. Explicit combination of multiple attributes yields composite scores. To evaluate the risk or probability of disease, they are useful. But the components of the scores can be combined only if they are mathematically isomorphic. For the evaluation of interventions, they are less useful because the effect on one component may be obscured by the lack of effect on other components. This article reviews quantification of air trapping in cystic fibrosis and quantification in general. Validation of any computer analysis can rely on agreement with visual interpreters (on average), they can be derived from first principles, or by agreement with an alternative method that measures the pathophysiological mechanism directly (xenon washout for air trapping). However, in the context of trials, the validation may come from a superior ability to detect objective change and to discriminate between affected and unaffected individuals.
Proceedings of the American Thoracic Society 09/2007; 4(4):347-9.
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ABSTRACT: Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled (131)I-fialuridine (FIAU), and of synergy between (131)I-FIAU and Ganciclovir (GCV).
HSV1-tk-expressing cell lines and parental cell lines were exposed to (131)I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied.
HSV1-tk-expressing cells accumulated up to 15.7-fold more (131)I-FIAU, were growth inhibited by 2 muCi/ml, or 5 muCi/ml (131)I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome.
Radioisotope therapy of HSV1-tk-expressing tumor cells with (131)I-FIAU is reported for the first time. Lack of synergy between (131)I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.
Molecular Imaging & Biology 04/2007; 9(3):110-6. · 3.84 Impact Factor
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ABSTRACT: While relative lung perfusion distributions are cited in clinical decision making for congenital and acquired pulmonary vascular diseases, normal values and ranges have not been published for a large population of normally perfused lungs. These values of normal relative perfusion will be useful for establishing what is abnormal and for clinical decisions related to various pulmonary vascular diseases.
Relative perfusion distributions were quantified for the top, middle, and bottom thirds of the right and left lungs with a semiautomatic algorithm in 206 normal scintigraphy lung studies (45 +/- 18 years, 149 female, 57 male) acquired between January 1, 2000 and March 30, 2004 in the Nuclear Medicine Division at Stanford Hospital and Clinics.
The perfusion data were found to be highly non-Gaussian in nature (necessitating the use of Wilcoxon statistical comparisons), and the right/left perfusion ratio was found to be 52.5/47.5 (+/-2.1%) rather than the often quoted 55/45 split. While this right/left split was consistent between the genders, males had proportionally less perfusion in the lower left lung as compared with females (P < .05).
The long-standing 55/45 right/left perfusion ratio assumption was found to be more than 1 standard deviation greater than the mean, and the population variance is very small. Relative pulmonary perfusion distribution varies significantly with lung region, gender, and age, and should be considered when making clinical decisions based on pulmonary perfusion.
Congenital Heart Disease 10/2006; 1(5):210-6. · 0.90 Impact Factor
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Hilary Hardy Street, Michael L Goris,
George Albert Fisher,
Barry W Wessels,
Cheryl Cho,
Carmen Hernandez,
Hongyun June Zhu,
Yuxia Zhang,
Jasvinder Singh Nangiana,
Joseph S Shan,
Karen Roberts,
Susan J Knox
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ABSTRACT: The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues.
Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg).
The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses.
The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.
Cancer Biotherapy and Radiopharmaceuticals 07/2006; 21(3):243-56. · 1.79 Impact Factor
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ABSTRACT: The first aim of the study was to determine whether (99m)Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury.
SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 microg i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery.
Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r (2)=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r (2)=0.728, p=0.00084).
Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials.
European journal of nuclear medicine and molecular imaging 06/2006; 33(5):566-74. · 4.99 Impact Factor
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ABSTRACT: To evaluate quantitative air trapping measurements in children with mild cystic fibrosis (CF) lung disease during a 1-year, double-blind, placebo-controlled, recombinant human deoxyribonuclease (rhDNase) [dornase alfa] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT (HRCT) scans of the chest.
Twenty-five children with CF randomized to either daily rhDNase or placebo aerosol were evaluated at baseline, and at 3 months and 12 months by spirometer-triggered HRCT and spirometry. Outcome variables were percentage of predicted FVC, FEV1, and forced expiratory flow, midexpiratory phase (FEF(25-75%)); total and subcomponent visual HRCT scores; and quantitative air trapping measurements derived from chest HRCT images.
At baseline, there were no statistical differences between groups in any of the variables used as an outcome. After 3 months of treatment, both groups had improvements in percentage of predicted FEV1 and FEF(25-75%), and total HRCT visual scores. In contrast, the rhDNase group had a 13% decrease in quantitative air trapping from baseline (severe air trapping [A3]), compared to an increase of 48% in the placebo group (p = 0.023). After 12 months, both groups had declines in percentage of predicted FVC and FEV1, but the rhDNase group retained improvements in percentage of predicted FEF(25-75%) and quantitative air trapping. The mucus plugging and total HRCT visual scores were also improved in the rhDNase group after 12 months of treatment, with and without significant differences between groups (p = 0.026 and p = 0.676). Quantitative air trapping (A3) remained improved in the rhDNase group (- 15.4%) and worsened in the placebo group (+61.3%) with nearly significant differences noted between groups (p = 0.053) after 12 months of treatment.
Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.
Chest 11/2005; 128(4):2327-35. · 5.25 Impact Factor
