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Abass Alavi

Publications and source records attributed to Abass Alavi.

At least 73 records · Page 4Linked to original sources

In vivo detection of stem cells grafted in infarcted rat myocardium.

UNLABELLED: The evaluation of stem cell-mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of (99m)Tc-sestamibi to assess myocardial perfusion and of (111)In-labeled stem cells to delineate stem cell engraftment. METHODS: Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1-14.8 MBq (0.3-0.4 mCi) of (111)In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. (111)In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of (99m)Tc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image (99m)Tc-sestamibi uptake simultaneously with (111)In to delineate retention of (111)In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. RESULTS: SPECT of (99m)Tc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull's-eye plots indicated that the (111)In signal from the labeled stem cells overlapped the perfusion deficits identified from the (99m)Tc-sestamibi images. The (111)In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. CONCLUSION: This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with (99m)Tc-sestamibi and with (111)In-labeled stem cells grafted into the region of the infarct.

Animals↗

123I-ADAM binding to serotonin transporters in patients with major depression and healthy controls: a preliminary study.

UNLABELLED: The serotonergic system may play an important role in the pathophysiology of major depressive disorder (MDD). Few imaging studies have examined serotonin transporter (SERT) binding in patients with MDD. We hypothesized that SERT binding activity may be altered in patients with MDD. This study compared SERT binding in patients with MDD with that in healthy controls. METHODS: We studied SERT activity in 7 patients (22-50 y old) with moderate to severe MDD and 6 healthy controls (24-56 y old) using (123)I-labeled 2-((2-((dimethylamino)methyl) phenyl)thio)-5-iodophenylamine (ADAM) and SPECT brain imaging. Subjects underwent SPECT 4 h after intravenous administration of 185 MBq (5 mCi) of (123)I-ADAM. Images were reconstructed in the axial plane, and region-of-interest demarcations were placed on the midbrain, medial temporal region, and basal ganglia region. RESULTS: (123)I-ADAM binding to SERT in the midbrain was significantly lower (P = 0.01) in MDD patients (1.81 +/- 0.07) than in controls (1.95 +/- 0.13). Age-adjusted (123)I-ADAM binding in the midbrain correlated significantly with scores on the Hamilton Depression Rating Scale (r = 0.82; P = 0.02). A significant negative correlation was observed between (123)I-ADAM SERT binding in the midbrain and age in the healthy control group (r = 0.98; P = 0.0002). SERT binding in the basal ganglia or medial temporal regions of interest did not significantly differ between groups. CONCLUSION: The findings from this preliminary study suggest the possibility of decreased SERT binding in the midbrain region of patients with MDD, with the degree of decrease correlating with the severity of depressive symptoms. There also appears to be an age-related decline in midbrain (123)I-ADAM SERT binding in healthy subjects.

Adult↗

Potential of dual-time-point imaging to improve breast cancer diagnosis with (18)F-FDG PET.

UNLABELLED: The purpose of this study was to assess the utility of dual-time-point imaging for identifying malignant lesions in the breast by (18)F-FDG PET. METHODS: Fifty-four breast cancer patients with 57 breast lesions underwent 2 sequential PET scans (dual-time-point imaging). The average percent change in standardized uptake values (SUVs) between time point 1 and time point 2 was calculated. All PET study results were correlated with follow-up surgical pathology results. RESULTS: Of the 57 breast lesions, 39 were invasive carcinoma and 18 were postbiopsy inflammation. Among the invasive carcinoma lesions, 33 (85%) showed an increase and 6 (15%) showed either no change or a decrease in SUVs over time. The percent change in SUVs from time point 1 to time point 2 (mean +/- SD) was +12.6% +/- 11.4% (P = 0.003). Of the 18 inflammatory lesions, 3 (17%) showed an increase and 15 (83%) showed either no change or a decrease in SUVs. The percent change in SUVs from time point 1 to time point 2 (mean +/- SD) was -10.2% +/- 16.5% (P = 0.03). Of the 57 normal contralateral breasts, 2 (3.5%) showed an increase and 55 (96.5%) showed either no change or a decrease in SUVs. The percent change in SUVs from time point 1 to time point 2 (mean +/- SD) was -15.8% +/- 17% (P = 0.005). CONCLUSION: There is increasing uptake of (18)F-FDG over time in breast malignancies, whereas the uptake of (18)F-FDG in inflammatory lesions and normal breast tissues decreases over time. A percent change of +3.75 or more in SUVs over time is highly sensitive and specific in differentiating inflammatory lesions from malignant lesions.

Adult↗

Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent.

The 11C-labeled sulfonylurea receptor 1 (SUR1) ligand (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide) was synthesized in an overall radiochemical yield of 35% after 55 min with a radiochemical purity higher than 99%. This compound is considered for the noninvasive investigation of the SUR1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. The specific activity was 40-70 GBq/micromol. In vitro testing of the nonradioactive methoxy-repaglinide was performed to characterize the affinity for binding to the human SUR1 isoform. Methoxy-repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (KD) of 83 nM and an IC50 of 163 nM. Insulin secretion experiments on isolated rat islets were performed to prove biological activity, which was determined to be in the same range as that of original repaglinide.

ATP-Binding Cassette Transporters↗

Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson's disease.

PURPOSE: Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [99mTc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders. METHODS: Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Student's t tests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures. RESULTS: Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p<0.05) than in PD patients. In particular, the MSA patients had significantly increased DVRs in the posterior putamen (mean 0.49+/-0.30) compared with PD patients (0.74+/-0.25). CONCLUSION: Movement disorder patients could be differentiated from controls, but MSA and PD patients could not be easily differentiated from each other. As a group, MSA patients had significantly higher mean [99mTc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases.

Adult↗

Akt stimulates aerobic glycolysis in cancer cells.

Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.

Aerobiosis↗

Normal variants in [18F]-fluorodeoxyglucose PET imaging.

The number of fluorodeoxyglucose PET applications is increasing. In the process of reading fluorodeoxyglucose-PET scans, nuclear medicine physicians encounter a wide variety of normal findings, which must be recognized to determine the best management for patients. It is important to recognize and understand normal variants to avoid misinterpretation of more serious pathology. This article reviews different patterns of physiologic fluorodeoxyglucose uptake including changes with age.

Aging↗

Investigation of thyroid, head, and neck cancers with PET.

PET with [(18)F]-fluorodeoxyglucose (FDG) has been accepted as a useful imaging modality for the diagnosis of a variety of malignancies. This article discusses the use of FDG-PET in the management of patients with thyroid and head or neck cancers.

Fluorodeoxyglucose F18↗

Fluorodeoxyglucose-PET in the management of breast cancer.

FDG-PET can be helpful in the diagnosis of primary breast cancer, especially in patients with dense breast tissue, significant fibrocystic changes, fibrosis after radiotherapy, and inconclusive results from MR imaging and other imaging modalities. PET has a limited role in patients with very small tumors and with well-differentiated and lobular types of breast cancer. In preoperative staging, FDG-PET has a low sensitivity for detection of regional lymph node involvement. Also, current PET imaging techniques can easily miss micrometastases. FDG-PET, however, has high positive predictive value for the axillary lymph node involvement, especially patient with advanced tumors. Compared with conventional imaging modalities, FDG-PET provides high diagnostic accuracy in detecting recurrent or metastatic breast carcinoma. FDG-PET seems to be highly useful for monitoring response to therapeutic interventions. This technique can identify response to therapy earlier than any other imaging method currently available. Obviously, identification of nonresponding patients could greatly improve patient management by allowing termination of ineffective and toxic therapies.

Breast Neoplasms↗

PET imaging in gynecologic malignancies.

FDG-PET has a definite role in detecting lymph node involvement and distant metastases. It has also shown encouraging results in assessing tumor recurrence and restaging, but further studies are required before FDG-PET can be incorporated in routine clinical practice for diagnosis of recurrence. In ovarian cancer, FDG-PET has high sensitivity and specificity in identifying patients with recurrent tumor, but lesion localization is difficult with PET. Normal FDG activity in the gastrointestinal tract and bladder may obscure some lesions. Combined PET/CT can help in localizing lesions and differentiating between pathologic and physiologic uptake in the pelvis and abdomen.

Female↗

PET in the management of urologic malignancies.

FDG-PET has a limited role in diagnosis of prostate cancer mainly because of the low uptake of FDG in the tumor and normal excretion of FDG through urine. FDG-PET has shown some promise in the assessment of lymph nodes and bone metastases. There is a large degree of variability when FDG-PET is compared with bone scintigraphy. New C11-labeled radiotracers (acetate, choline, and methionine) have shown promising initial results but further studies are required to determine their role in such settings. These radiotracers provide a unique opportunity for dynamic, multitracer, and quantitative studies, which improve the sensitivity and specificity on PET in this population. Short half-lives and of C-11, however with the limits to their use requires an on-site cyclotron. Recent synthesis schemes with [18F]-labeling, however, may overcome this limitation. FDG-PET has a significant potential to assist with the diagnosis and management of testicular cancer. PET has been most useful in defining the presence or absence of disease in patients with residual masses. PET has shown promising results for the initial diagnosis of this cancer, but further for studies ar required to determine its role in the management of this malignancy. PET can be used in conjunction with conventional imaging techniques to diagnose retroperitoneal masses in patients with primary testicular cancer. FDG-PET has shown very encouraging results in a limited number of studies, and has also demonstrated a good sensitivity for initial staging. FDG-PET seems to be superior to conventional imaging modalities for detecting local disease and recurrence, and distant metastases.

Carbon Radioisotopes↗

Utility of fluorodeoxyglucose-PET imaging in the management of patients with Hodgkin's and non-Hodgkin's lymphomas.

FDG-PET imaging has a number of advantages in the management of patients with lymphoma. PET shows a functional metabolic status and gives quantitative information. In addition, PET provides whole-body images that give a comprehensive assessment of disease extent during the staging and followup. Based on the present literature, FDG-PET is at least equivalent to CT for the initial staging of lymphomas. The impact of new technologies of combined PET/CT and fast-scanning CT with contrast has yet to be evaluated in the management of lymphoma patients, however. At this point, FDG-PET and CT must be considered as giving complementary staging information. FDG-PET also has high diagnostic accuracy for restaging lymphoma after initial treatment. FDG-PET has shown high accuracy in the early prediction of response to chemotherapy and in the evaluation of residual masses after chemotherapy or radiation therapy. Therefore, PET is likely to play a major role in tailoring the intensity of the treatment to the individual patient. A pretreatment FDG-PET study is essential for accurate assessment of residual masses and early monitoring of response to the treatment. In addition, a baseline PET scan will help detect relapse or residual disease, because relapse occurs most often in the region of previous disease.

Fluorodeoxyglucose F18↗

Quantification in PET.

Quantification provides the link between the concentrations of radioactivity measured in tissue and the underlying physiologic processes occurring in the organ. It relates the rate at which radioactivity levels in the body change over time to quantitative parameters such as absolute rate glucose metabolism, regional blood flow, or concentrations of receptors or other binding sites. Absolute measurement of physiologic parameters generally requires accurate measurement of activity concentrations in arterial blood, which provides the input function to the kinetic model. Although absolute quantification can be a difficult process, simplifications of these invasive techniques, involving reference tissues or normalization approaches (eg, SUV), have been applied with some success. Any simplified model of tracer behavior must be validated against the full model to test for bias and systematic errors.

Algorithms↗

PET: a revolution in medical imaging.

FDG-PET has had remarkable influence on the assessment of physiologic and pathologic states. The authors predict that FDG-PET imaging could soon become the most common procedure used by nuclear medicine laboratories and could remain so for an extended period of time. The power of molecular imaging lies in the vast potential for using biochemical and pharmacologic probes to extend applications arising from an understanding of cell biology to a large number of well-characterized pathologic states. Molecular imaging based upon tracer kinetics with positron-emitting radiopharmaceuticals could become the main source of information for the management of cancer patients. In that case, nuclear medicine procedures might become the most common imaging studies performed in the practice of medicine. This speculation is not farfetched when one realizes the enormous change that a single biologically important compound, FDG, has brought to the medical arena. The major challenge today is to attract the highly qualified individuals and to secure the resources needed to harness the opportunities in the specialty of molecular imaging.

Fluorodeoxyglucose F18↗

PET imaging I.

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Animals↗

Implications of PET based molecular imaging on the current and future practice of medicine.

The last quarter century has witnessed the introduction of a variety of powerful techniques that have allowed visualization of organ structure and function with exquisite detail. This in turn has brought about a true revolution in the day-to-day practice of medicine. Structural imaging with x-ray computerized tomography and magnetic resonance imaging has added tremendously to many areas of medicine, including preoperative evaluation of patients. Many surgical procedures have been replaced by minimally invasive techniques, which have become a reality only because of the availability of modern imaging modalities. However, despite such accomplishments, structural imaging is quite insensitive for detecting early disease in which there often are no gross structural alterations in organ anatomy. Therefore, these modalities should be complemented by methodologies that can detect abnormalities at the molecular and cellular levels. The introduction of [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in 1976 as a molecular imaging technique clearly has shown the power of this approach for treating a multitude of serious disorders. The impact of FDG-PET has been particularly impressive in patients with cancer diagnosis, for whom it has become important in staging, monitoring response to treatment, and detecting recurrence. In this review, we emphasize the role of FDG-PET in the assessment of central nervous system maladies, malignant neoplastic processes, infectious and inflammatory diseases, and cardiovascular disorders. New radiotracers are being developed and promise to expand further the list of indications for PET. These include novel tracers for cancer diagnosis and treatment capable of detecting hypoxia and angiogenesis. Prospects for developing new tracers for imaging other organ diseases also appear very promising.

Animals↗

Evolving role of positron emission tomography in the management of patients with inflammatory and other benign disorders.

Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has evolved from a research imaging modality assessing brain function in physiologic and pathologic states to a pure clinical necessity. It has been successfully used for diagnosing, staging, and monitoring a variety of malignancies. FDG-PET imaging also is evolving into a powerful imaging modality that can be effectively used for the diagnosis and monitoring of a certain nononcological diseases. PET has been shown to be very useful in the diagnosis of osteomyelitis, painful prostheses, sarcoidosis, fever of unknown etiology, and acquired immunodeficiency syndrome. Based on recent observations, several other disorders, such as environment-induced lung diseases, atherosclerosis, vasculitis, back pain, transplantation, and blood clot, can be successfully assessed with this technique. With the development and the introduction of several new PET radiotracers, it is expected that PET will secure a major role in the management of patients with inflammatory and other benign disorders.

Bacterial Infections↗