J B Alavi

University of Pennsylvania, Philadelphia, PA, United States

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Publications (20)78.5 Total impact

  • J B Alavi, S L Eck
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    ABSTRACT: High grade gliomas in adults are devastating diseases, with very poor survival despite their lack of distant metastases. Local treatments, such as surgical resection and stereotactic radiosurgery, have been most successful, whereas systemic therapy (for example, chemotherapy and immunotherapy) have been rather disappointing. Several gene therapy systems have been successful in controlling or eradicating these tumours in animal models and are now being tested as a logical addition to current clinical management. This review describes the gene therapy clinical protocols that have been completed or that are ongoing for human gliomas. These include the prodrug activating system, herpes simplex thymidine kinase (HSVtk)/ganciclovir (GCV), utilising either retrovirus vector producer cells or adenovirus vectors; adenovirus mediated p53 gene transfer; adenovirus mediated IFN-beta gene transfer and oncolytic herpes virus and adenovirus vectors. To date, all of the clinical studies have used direct injection of the vector into the glioma. The Phase I clinical studies have demonstrated low to moderate toxicity and variable levels of gene transfer and in some cases anti-tumour effect. Future directions will rely upon improvements in gene delivery as well as gene therapies and combinations of gene therapy with other treatment modalities.
    Expert Opinion on Biological Therapy 04/2001; 1(2):239-52. · 3.35 Impact Factor
  • Human Gene Therapy 02/2001; 12(1):97-113. · 4.02 Impact Factor
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    ABSTRACT: An unusual cause of abdominal soft-tissue masses is accessory splenic tissue. The Tc-99m-sulfur colloid liver-spleen scan is a valuable adjunct in making this diagnosis. This report describes a 47-year-old man who had an abdominal magnetic resonance imaging (MRI) scan as part of a pretransplant evaluation and was found to have multiple soft-tissue masses in the posterior aspect of his abdomen. His history was pertinent for a traumatic rupture of the spleen at the age of 12 years, for which he required a splenectomy. He had no symptoms or physical findings to indicate a lymphoproliferative disorder or other malignant process. His peripheral blood smear was remarkable for the absence of Howell-Jolly bodies. The nuclear scan confirmed the presence of uptake in the soft-tissue masses seen on MRI scan. This finding supports our diagnosis of splenosis in a man with a history of traumatic splenic rupture as a child.
    American Journal of Clinical Oncology 11/2000; 23(5):506-8. · 2.55 Impact Factor
  • A B Newberg, A Alavi, J Alavi
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    ABSTRACT: Contralateral cerebellar diaschisis, hypometabolism in the cerebellum contralateral to a cortical lesion, is a well described phenomenon in patients with stroke and brain tumor. However, few reports exist of patients with cerebellar lesions with the finding of contralateral cortical hypometabolism. The authors present a case of a patient with a right cerebellar astrocytoma after surgical resection and radiation therapy in which fluorine-18 fluorodeoxyglucose positron emission tomographic imaging, performed to rule out recurrent tumor, revealed global hypometabolism in the left cerebral cortex. The concept of contralateral cortical diaschisis and possible mechanisms and clinical implications are reviewed.
    Clinical Nuclear Medicine 07/2000; 25(6):431-3. · 2.96 Impact Factor
  • J B Alavi, S L Eck
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    ABSTRACT: Malignant gliomas are attractive targets for gene therapy because of their relatively well-localized distribution. Several new strategies have been devised that target different aspects of glioma biology. Gene transfer can be used to synthesize chemotherapy drugs that block DNA synthesis within these highly mitotic tumors. New genes can be introduced that restore the functions of mutated tumor suppressor genes or block the molecular pathways needed for tumor angiogenesis. Alternatively, the immune response to these tumors can be augmented by the local production of cytokines. Finally, viruses themselves can be used as tumoricidal agents by designing viruses that selectively replicate and destroy tumor cells. The advantages and limitations of these approaches are discussed in the context of their possible application to the treatment of these highly lethal malignancies.
    Hematology/Oncology Clinics of North America 07/1998; 12(3):617-29. · 2.08 Impact Factor
  • J B Alavi, F Bénard, A Alavi
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    ABSTRACT: We performed a fluorodeoxyglucose-positron emission tomographic (FDG-PET) study on a patient who had high-grade lymphoma thought to be in complete remission. The patient underwent the PET study before being considered for high-dose consolidation therapy because he was thought to be at high risk for relapse. The whole-body FDG-PET study revealed an unsuspected hypermetabolic mass in the lower spine that was not visualized on computed tomographic (CT) scanning. The other laboratory values were normal, with the exception of mild lactate dehydrogenase elevation. Two weeks later, the patient developed low back pain, and magnetic resonance imaging showed a 2-cm paraspinal mass at the level of L4. Bone-marrow biopsy confirmed recurrent lymphoma. Remission was not achieved after another chemotherapy regimen. Fluorodeoxyglucose-positron emission tomography can be helpful in the restaging of lymphoma patients after induction chemotherapy and may help to detect early recurrence in selected situations.
    American Journal of Clinical Oncology 04/1998; 21(2):126-8. · 2.55 Impact Factor
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    ABSTRACT: Primary CNS malignancies are responsible for approximately 12,000 deaths annually in the United States. There has been little change in the outcome for adults with malignant brain tumors over the past few decades, despite improvements in surgical techniques and advances in radiation therapy. These tumors are uniformly fatal one to two years after diagnosis. The morbidity and mortality of this disease arise from the effects of a locally invasive, non-metastasizing lesion. The patients may suffer from seizures, paralysis, incoordination, aphasia, confusion, memory loss, sensory deficits or visual loss, depending on the regions of the brain affected. In addition, they usually require large doses of corticosteroids early and late in their illness, and may experience disabling side effects of this treatment, such as edema, proximal myopathy, diabetes, fungal infections or deep vein thrombosis. Few patients in the older age group are able to work after the diagnosis. Most of the patients are incapable of self-care for several months before death. The localized transfer of new genes into cancer cells potentially permits the expression of proteins with specific biologic functions that may provide a means to alter the biology of tumor growth through a variety of mechanisms including increasing tumor immunogenicity, inducing the local expression of toxic agents, and sensitization of tumors to chemotherapeutic agents. Gene therapy with the transfer of the drug susceptibility gene Herpes virus thymidine kinase (HSV-TK) has shown promise in a number of animal models, including CNS tumors. This study will evaluate the use of adenovirus-mediated transfer of the HSV-TK gene into primary human brain tumors followed by systemic treatment with ganciclovir. The goals of this phase I study are to evaluate the overall safety and efficacy of this treatment and to gain insight into the parameters that may limit the general applicability of this approach. In this phase I study, patients with recurrent gliomas will receive stereotactic-guided injections of the virus into the brain tumor, followed by intravenous ganciclovir for 14 days. Patients eligible to undergo a palliative debulking procedure will receive the same treatment followed by resection on day 7. At the time of resection a second dose of virus will be administered intra-operatively into the residual, unresectable portion of the tumor, and intravenous ganciclovir will be continued for additional 14 days. Tissue removed at the time of resection will be analyzed for evidence of adenovirus infection, thymidine kinase expression and signs of inflammation. The size and metabolic activity of all tumors will be followed by volumetric MRI scans and Position Emission Tomography Scans, respectively. Patients will be enrolled in groups of three, with each group receiving successively larger doses of adenovirus. This study will quantify the toxicity of this therapy, and provide evidence as to the duration of transgene expression and virus induced inflammation.
    Human Gene Therapy 09/1996; 7(12):1465-82. · 4.02 Impact Factor
  • International Journal of Radiation Oncology Biology Physics - INT J RADIAT ONCOL BIOL PHYS. 01/1996; 36(1):195-195.
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    ABSTRACT: Two cases of postsurgical brain tumor evaluation in which MRI was inconclusive are discussed. Functional imaging techniques, such as FDG-PET and 201TI SPECT, were used in both cases for distinguishing radiation necrosis from tumor recurrence. These methods proved to be complimentary. For Patient 1, FDG-PET showed more limitations compared to 201TI SPECT. FDG-PET results on the other hand, were consistent with the final diagnosis and the SPECT image was false positive for tumor recurrence in Patient 2.
    Journal of Nuclear Medicine 02/1995; 36(1):159-64. · 5.77 Impact Factor
  • C.A. Buchpiguel, J.B. Alavi, A. Alavi
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    ABSTRACT: CT and MRI scans are quite sensitive in detecting brain tumors. However, with both imaging techniques limitations have been reported in distinguishing tumor recurrence from radiation necrosis. Metabolic imaging methods such as PET-FDG and SPECT T1-201 have been utilized for differentiating radiation necrosis from tumor recurrence. However, no study was to compare PET-FDG and SPECT T1-201 in primary brain tumors.
    Journal of Nuclear Medicine 04/1994; 35(Suppl.5). · 5.77 Impact Factor
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    ABSTRACT: Conventional radiologic and nuclear medicine techniques have been shown to have a limited role in the staging and monitoring of disease activity in patients with lung cancer. Both qualitative and semi-quantitative position emission tomography (PET) using the F-18 FDG technique have been applied to determine the clinical utility of whole body PET-FDG imaging in lung cancer. Nineteen whole body FDG PET scans were performed in 18 patients; 17 with lung cancer (15 non-small cell and 2 small cell) and 1 with squamous cell carcinoma of the trachea.
    Journal of Nuclear Medicine 04/1994; 35(Suppl.5). · 5.77 Impact Factor
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    ABSTRACT: Although radiotherapy (XRT) is a necessary course of treatment to prolong life expectancy in patients with many types of brain neoplasms, it has damaging effects that are little understood. We used a comprehensive neuropsychological battery to evaluate five patients with low-grade brain tumors prior to XRT and then at 3-month intervals up to 9 months postcompletion of XRT. We matched patients by age and education with six normal control subjects to assess baseline impairment. In intrasubject comparisons, we examined change over time postcompletion of XRT. In spite of varying locations of tumors, all patients showed deterioration in long-term memory at a mean of 1.5 months postcompletion of XRT. Patients also consistently demonstrated a rebound effect between means of 4.7 and 7.6 months post-XRT. We found no changes over time in working memory, attention, visuospatial processes, or on any other neuropsychological test with the exception of information-processing speed, which quickened over time. Functional measures of fatigue and mood did not correlate significantly with the long-term memory scores. Long-term memory appears sensitive to the proposed white matter changes thought to be the mechanism for the early-delayed effects of XRT. Our findings suggest a neurobehavioral model for studying the effects of XRT on brain functioning.
    Neurology 11/1993; 43(10):1961-5. · 8.25 Impact Factor
  • C K Kim, J B Alavi, A Alavi, M Reivich
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    ABSTRACT: Positron emission tomography (PET) using fluorine-18 (18F)-fluorodeoxyglucose (FDG) has been reported to be a powerful diagnostic and prognostic tool in patients with primary brain tumors. This study was undertaken to compare the prognostic value of: (1) visual grading of [18]FDG uptake in the tumor, (2) the absolute glucose metabolic rate of the tumor (TMRglc), (3) the ratio of glucose metabolism between the tumor and whole brain (T/WB) and (4) between the tumor and contralateral cerebellum (T/CBL). Each of these four parameters was correlated with the survival time in 20 patients with malignant cerebral gliomas. Excellent correlation was obtained with visual grading and reasonably good correlation was obtained with T/WB or T/CBL, but TMRglc alone was only a fair prognostic indicator. Thus, visual grading provides a qualitative analysis and T/WB provides a semi-quantitative analysis neither of which requires arterial blood sampling for quantification of absolute metabolic rates for glucose.
    Journal of Neuro-Oncology 03/1991; 10(1):85-91. · 3.12 Impact Factor
  • A Alavi, J B Alavi, R E Lenkinski
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    ABSTRACT: Short communication.
    Radiology 01/1991; 177(3):617-8. · 6.34 Impact Factor
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    Journal of Nuclear Medicine 04/1990; 31(3):360-4. · 5.77 Impact Factor
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    ABSTRACT: Positron emission tomography (PET) studies have been performed using 18-F-fluorodeoxyglucose in 29 adult subjects with primary brain tumors. Seventy-two percent of the patients were treated previously. The glucose metabolic state in the lesions was increased in 16 patients, and was normal or decreased in 13 patients. The hypermetabolic tumors tended to behave in a more malignant fashion. Patients with hypermetabolic tumors had a median survival of 7 months after PET scan, compared to 33 months for those with hypometabolic lesions. Among the high-grade glioma patients, the PET results separated them into a good prognosis group (hypometabolic, with 78% 1-year survival) and a poor prognosis group (hypermetabolic, with a 29% 1-year survival after PET). These results suggest that glucose metabolic studies may provide an independent measure of the aggressiveness of a brain tumor, and may supplement pathologic grading.
    Cancer 10/1988; 62(6):1074-8. · 5.20 Impact Factor
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    ABSTRACT: We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ([18F]FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.
    Journal of Nuclear Medicine 12/1987; 28(11):1667-70. · 5.77 Impact Factor
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    ABSTRACT: Computerized tomography (CT) and positron emission tomography (PET) using fluorine-18-deoxyglucose were performed in a patient with malignant glioma over a one-year period. Postoperatively and during radiation therapy, there was slight improvement in metabolic activity in the hemisphere ipsilateral to the tumor. After radiation therapy and during chemotherapy, there was a rapid and then gradual decline in whole brain metabolic rate by 39%. This might have been explained by radiation effect on brain. The tumor area was metabolically similar to the adjacent brain until one year after diagnosis, when an area of abnormal increased activity was noted. Even though CT scans showed minimal evidence of tumour growth, a large glioblastoma multiforme was found at autopsy at the site of the increased activity. Radiation leukoencephalopathy was also observed at autopsy. It is concluded that PET studies may offer new information regarding the metabolic effects of anti-tumor therapy, and may demonstrate regrowth of tumor prior to CT.
    Nuclear Medicine Communications 08/1987; 8(7):457-68. · 1.38 Impact Factor
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    ABSTRACT: The (F-18) fluorodeoxyglucose (FDG) technique to measure local cerebral metabolic rate for glucose (LCMRglu) is well accepted and widely used by many institutions around the world. A large number of studies has been carried out in normal volunteers and patients with a variety of CNS disorders. Several investigators have noted that no significant age-related changes in cerebral glucose use occur with normal aging. Some important and interesting findings have been revealed following sensory, motor, visual, and auditory stimulations. Functional imaging with FDG in certain neurologic disorders has dramatically improved our understanding of their underlying pathophysiologic phenomena. Some abnormalities detected on the positron emission tomography (PET) images have no corresponding changes on either x-ray computed tomograms (XCT) or magnetic resonance images (MRI). In patients with Alzheimer's disease, primary sensorimotor, visual, and cerebellar metabolic activity appears relatively preserved. In contrast, parietal, temporal, and to some degree, frontal glucose metabolism is significantly diminished even in the early stages of the disease. Patients with Huntington's disease and those at risk of developing this disorder have a typical pattern of diminished CMRglu in the caudate nuclei and putamen. In patients with stroke, PET images with FDG have demonstrated abnormal findings earlier than either XCT or MRI and with a wider topographic distribution. FDG scans have revealed interictal zones of decreased LCMRglu in approximately 70% of patients with partial epilepsy. The location of the area of hypometabolism corresponds to the site of the epileptic focus as determined by electroencephalography and microscopic examination of the resected tissue. Ictal scans during partial seizures demonstrate areas of hypermetabolism corresponding to the sites of seizure onset and spread. Several investigators have reported relative hypofrontal CMRglu in patients with schizophrenia. In our center, FDG scans from patients with schizophrenia were successfully differentiated from those obtained in normal controls. Finally, our preliminary data (using PET, XCT, and MRI) in patients with CNS disorders indicate that MRI provides excellent delineation of the structural abnormalities. It may prove to be superior to XCT in the evaluation of certain diseases such as cerebral ischemia and infarcts, head injury, tumors, and white matter lesions. Metabolic imaging with FDG provides functional information not obtainable with either MRI or NMR spectroscopy. Therefore, PET studies will play a complementary role to the anatomic imaging in the management of patients with CNS disorders.
    Seminars in Nuclear Medicine 02/1986; 16(1):2-34. · 3.82 Impact Factor
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    ABSTRACT: Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1 enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.
    04/1985

Publication Stats

549 Citations
78.50 Total Impact Points

Institutions

  • 1987–2001
    • University of Pennsylvania
      • • Division of Hematology/Oncology
      • • Department of Medicine
      • • Department of Radiology
      • • Department of Neurology
      Philadelphia, PA, United States
  • 1986–2000
    • Hospital of the University of Pennsylvania
      • • Department of Radiology
      • • Department of Medicine
      Philadelphia, PA, United States