indium-oxine and Brain-Neoplasms

Treatment options of glioblastoma multiforme are limited due to the blood-brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell-based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. ¹¹¹In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of (¹¹¹In)-oxine-labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell-based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Cell Tracking; Chemokine CXCL12; Disease Models, Animal; Gamma Rays; Gene Expression; Glioma; Humans; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Organometallic Compounds; Oxyquinoline; TNF-Related Apoptosis-Inducing Ligand; Xenograft Model Antitumor Assays

Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. The efficacy of this therapy is based on the uptake of photosensitizer by neoplastic tissue, its clearance from surrounding brain tissue, and the timing and placement of photoactivating sources. Photofrin-II is the photosensitizer most actively being investigated. We labeled Photofrin-II with Indium-111 and studied the uptake and distribution of this agent in 20 patients with intracranial neoplasms, using single photon emission computed tomography (SPECT) with volume rendering in three dimensions. Of these patients, 16 had malignant glial tumors, 2 had metastatic deposits, 1 had a chordoma, and 1 had a meningioma. Anatomical-spatial data correlated well between the SPECT images and contrast-enhanced computed tomography or magnetic resonance images. Regions of focal uptake on SPECT images correlated with the surgical histopathological findings of the neoplasm. The kinetics of photosensitizer uptake varied according to the tumor's histological findings, the patient's use of steroids, and among patients with similar types of tumor histology. Peak ratios of target-to-nontarget tissue varied from 24 to 72 hours after injection. The study data show that, to be most effective, photodynamic therapy may need to be tailored for each patient by correlating SPECT images with anatomical data produced by computed tomography or magnetic resonance images. Photoactivating sources then can be placed, using computer-assisted stereotactics, to activate a prescribed volume of photosensitized tumor at the optimal time for treatment.

Topics: Adult; Aged; Astrocytoma; Brain; Brain Neoplasms; Dihematoporphyrin Ether; Female; Glioblastoma; Glioma; Hematoporphyrin Photoradiation; Humans; Lung Neoplasms; Male; Meningioma; Metabolic Clearance Rate; Middle Aged; Neoplasm Recurrence, Local; Organometallic Compounds; Oxyquinoline; Tomography, Emission-Computed, Single-Photon

The differential diagnosis of intracerebral enhancing lesions on contrast computed tomography includes tumors, abscesses, and cerebrovascular accidents. Particularly important is the differentiation between tumor and abscess. While In-111 labeled leukocyte imaging is an accurate test for identification of foci of infection in general, the role of this procedure in the evaluation of the intracranial lesion is not well established. We undertook a retrospective review of 16 patients with contrast enhancing intracerebral lesions identified on computed tomography, who were also studied with labeled leukocyte imaging. Final diagnoses were: abscess (n = 2), primary brain tumor (n = 6), metastasis (n = 4), dermoid cyst (n = 1), and cerebral infarct (n = 3). There were two positive labeled leukocyte studies; both were cerebral abscesses. No labeled leukocyte activity was identified in any of the tumors or infarcts. We conclude that In-111 labeled leukocyte imaging is an accurate method of differentiating infectious from noninfectious causes of intracerebral lesions identified on computed tomography.

Topics: Adult; Aged; Aged, 80 and over; Brain Abscess; Brain Diseases; Brain Neoplasms; Cerebral Infarction; Female; Humans; Indium Radioisotopes; Leukocytes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Retrospective Studies; Tomography, X-Ray Computed

Sixteen patients with intracerebral mass lesions where computed tomography (CT) was not fully conclusive with respect to the differential diagnosis between brain tumor and abscess were examined with leukocyte brain scintigraphy (LBS). Autologous leukocytes were labeled with indium-111 oxinate and were reinjected intravenously; registration with a gamma camera was performed after 24 and 48 hours. In 10 of 11 patients with the final diagnosis of a brain tumor, no accumulation of radiolabeled leukocytes could be detected in the brain. In 4 of 5 patients with the final diagnosis of brain abscess, scintigraphy showed a pronounced increase of focal activity corresponding to the lesion demonstrated with CT. The reasons for the one false-positive and the one false-negative result are discussed, and it is concluded that LBS (a) can be used to detect intracranial infection and (b) may be a useful diagnostic tool for distinguishing between brain abscess and brain tumor.

Topics: Adult; Aged; Brain Abscess; Brain Neoplasms; Diagnosis, Differential; Female; Humans; Hydroxyquinolines; Indium; Leukocytes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Radioisotopes; Radionuclide Imaging; Time Factors