fibrin and Brain-Neoplasms

The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide.

Topics: Animals; Brain; Brain Neoplasms; Collagen; Contrast Media; Diffusion; Drug Design; Fibrin; Gadolinium; Glioma; Humans; Image Processing, Computer-Assisted; Kinetics; Ligands; Magnetic Resonance Imaging; Mice; Models, Chemical; Pentetic Acid; Thermodynamics; Water

The role of blood tests in identifying patients at high risk for post-operative venous thromboembolism is undefined. The aim of this study was to evaluate the correlation between pre-operative plasma levels of soluble fibrin polymers (SFP), as determined by a recently developed enzyme-linked immunosorbent assay (ELISA) assay (TpP), and the incidence of deep vein thrombosis (DVT) after elective neurosurgery. Blood samples for SFP assay were withdrawn on the day before surgery from 157 consecutive patients undergoing elective neurosurgery for brain or spinal tumour. Patients were randomized to subcutaneous enoxaparin (40 mg once daily) or placebo given for at least 7 days. All patients wore compression stockings. DVT was assessed by bilateral venography, performed on day 8 +/- 1. Thirty-four patients (21.7%) were found to have a DVT, proximal in 11 (7%) and isolated distal in 23. Patients with and without DVT had a plasma pre-operative SFP levels of 6.2 +/- 4.6 and 1.9 +/- 1.5 mg/ml respectively (mean +/- SD) (P < 0.001). SFP levels in patients with proximal and isolated distal DVT were 7.6 +/- 5.1 and 5.5 +/- 4.4 microg/ml, respectively (P = 0.22). SFP cut-off levels categorized patients into three classes of DVT incidence. The incidence of DVT was 7.4% (6 of 81) for SFP levels < 2 microg/ml, 20.4% (11 of 54) for levels between 2 and 4.5 microg/ml, and 77.3% (17 of 22) for levels > 4.5 microg/ml (P= 0.001, Cochran-Mantel-Haenszel test). We conclude that pre-operative SFP levels correlate with post-operative DVT in elective neurosurgery patients. Further studies are required to define whether pre-operative SFP measurement could be useful in patient management.

Topics: Adult; Aged; Biomarkers; Brain Neoplasms; Elective Surgical Procedures; Enoxaparin; Female; Fibrin; Humans; Italy; Male; Middle Aged; Neurosurgical Procedures; Risk Factors; Solubility; Spinal Neoplasms; Venous Thrombosis

Topics: Aged; Brain Neoplasms; Fibrin; Hematoma, Subdural; Humans; Lymphoma, Large B-Cell, Diffuse; Male

Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types.

Topics: Animals; Brain Neoplasms; Cell Death; Cell Line, Tumor; Cell Movement; Disease Progression; Fibrin; Glioblastoma; Humans; Mice, Nude; Spheroids, Cellular; Stem Cell Transplantation; Tissue Scaffolds; Treatment Outcome

Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. Nanoparticle diameter can significantly influence the delivery efficiency in tumor tissue. Decreasing nanoparticle size can improve the nanoparticle penetration in tumor tissue but decrease the nanoparticle retention effect. Therefore, small nanoparticles with high retention effect in tumor are urgently needed for effective GBM drug delivery. In present study, a small nanoparticle drug delivery system was developed by conjugating fibrin-binding peptide CREKA to Polyamidoamine (PAMAM) dendrimer, where PEGylated PAMAM is used as drug carrier due to its small size and good penetration in tumor and CREKA is used to target the abundant fibrin in GBM for enhanced retention in tumor. In vitro binding ability tests demonstrated that CREKA can significantly enhanced nanoparticle binding with fibrin. In vivo fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen slices fluorescence imaging further revealed that the CREKA-modified PAMAM achieved higher accumulation and deeper penetration in GBM tissue than unmodified one. These results indicated that the CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Dendrimers; Drug Delivery Systems; Fibrin; Glioblastoma; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Oligopeptides

Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7-micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1 h after administration, as confirmed via in vivo and ex vivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma-targeting potential of CREKA-micelles and provide the foundation for CREKA-mediated, targeted therapy of glioma.

Topics: Animals; Brain; Brain Neoplasms; Carbocyanines; Drug Carriers; Drug Delivery Systems; Fibrin; Glioblastoma; Male; Mice; Mice, Inbred C57BL; Micelles; Oligopeptides

For a nanoparticulate drug-delivery system, crucial challenges in brain-glioblastoma therapy are its poor penetration and retention in the glioblastoma parenchyma. As a prevailing component in the extracellular matrix of many solid tumors, fibrin plays a critical role in the maintenance of glioblastoma morphology and glioblastoma cell differentiation and proliferation. We developed a new drug-delivery system by conjugating polyethylene glycol-polylactic acid nanoparticles (NPs) with cysteine-arginine-glutamic acid-lysine-alanine (CREKA; TNPs), a peptide with special affinity for fibrin, to mediate glioblastoma-homing and prolong NP retention at the tumor site. In vitro binding tests indicated that CREKA significantly enhanced specific binding of NPs with fibrin. In vivo fluorescence imaging of glioblastoma-bearing nude mice, ex vivo brain imaging, and glioblastoma distribution demonstrated that TNPs had higher accumulation and longer retention in the glioblastoma site over unmodified NPs. Furthermore, pharmacodynamic results showed that paclitaxel-loaded TNPs significantly prolonged the median survival time of intracranial U87 glioblastoma-bearing nude mice compared with controls, Taxol, and NPs. These findings suggested that TNPs were able to target the glioblastoma and enhance retention, which is a valuable strategy for tumor therapy.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Fibrin; Glioblastoma; Humans; Lactates; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Oligopeptides; Paclitaxel; Polyethylene Glycols; Random Allocation; Survival Analysis; Xenograft Model Antitumor Assays

Cell-based therapies have intriguing potential for the treatment of a variety of neurological disorders. One such example is genetically engineered cytotoxic T lymphocytes (CTLs) that are being investigated in brain tumor clinical trials. The development of methods for CTL delivery is critical to their use in the laboratory and clinical setting. In our study, we determined whether CTLs can migrate through fibrin matrices and if their migration, survival, and function could be modulated by adding chemokines to the matrix. Our results indicated that CTLs can freely migrate through fibrin matrices. As expected, the addition of the monocyte chemotactic protein-1 (MCP-1), also known as chemokine C-C motif ligand 2 (CCL2), to the surrounding media increased egress of the CTLs out of the fibrin clot. Interleukin (IL) -2 and/or IL-15 embedded in the matrix enhanced T cell survival and further promoted T cell migration. The interleukin-13 receptor alpha 2 specific (IL-13R alpha2) T cells that traveled out of the fibrin clot retained the capacity to kill U251 glioma cells. In summary, CTLs can survive and migrate robustly in fibrin matrices. These processes can be influenced by modification of matrix constituents. We conclude that fibrin matrices may be suitable T cell carriers and can be used to facilitate understanding of T cell interaction with the surrounding microenvironment.

Topics: Brain Neoplasms; Cell Movement; Cell Survival; Cells, Cultured; Chemokine CCL2; Fibrin; Glioma; Humans; Interleukin-15; Interleukin-2; T-Lymphocytes, Cytotoxic

To compare a fibrin-targeted, high relaxivity gadolinium tetramer, EP-2104R, in terms of magnitude of contrast enhancement (CE) and temporal time course, to a conventional extracellular gadolinium chelate, in a brain glioma model at 1.5-T magnetic resonance imaging.. Six rats were evaluated, with each animal receiving (for separate studies) 0.05 mmol/kg gadopentetate dimeglumine (Gd DTPA or Magnevist) and 0.0125 mmol/kg of EP-2104R, with the 2 magnetic resonance examinations separated in each animal by 24 hours. The compound (EP-2104R) was synthesized using published methodology, being comprised of an 11 amino acid peptide derivatized at both the C- and N-termini with Gd-DOTA-like (Dotarem-like) moieties. T1-weighted scans were acquired precontrast and for 5 consecutive 2-minute intervals postcontrast, and subsequently at 15 and 20 minutes postcontrast.. Maximum tumor contrast-to-noise and CE both occurred at 1 minute versus at 5 minutes following administration of Gd DTPA versus EP-2104R, respectively. Utilizing an equivalent dose on a Gd ion per body weight basis, signal-to-noise, contrast-to-noise, and CE were greater for EP-2104R at all time points postcontrast, yielding overall statistically significantly greater levels of all 3 parameters with the latter. With EP-2104R, improvements in CE ranged between 87% and 391%, increasing at each measured time postcontrast with the exception of a slight decrease from 15 to 20 minutes postadministration. Histopathology confirmed, using immunofluorescence technique, abnormally increased fibrin within the tumor.. Statistically significantly greater brain tumor enhancement was noted with greater lesion enhancement at all observed time points postcontrast for EP-2104R utilizing an equivalent concentration to Gd DTPA on a per gadolinium ion basis. These findings together with the prolonged time course of enhancement suggest possible fibrin-binding and altered distribution kinetics.

Topics: Animals; Area Under Curve; Brain Neoplasms; Contrast Media; Disease Models, Animal; Fibrin; Fluorescent Antibody Technique, Direct; Gadolinium DTPA; Glioma; Heterocyclic Compounds; Organometallic Compounds; Rats; Rats, Inbred F344

For tumor growth, proteolytic remodeling of the extracellular matrix (ECM) is a key factor. To determine proteolytic activity in human glioma cells, fibrinolytic activity, mRNA expression of fibrinolytic factors, and fibrinolytic inhibitors were studied in human glioma cell lines. The effect of platelet activating factor (PAF), a potent mediator of inflammatory and immune responses, on this fibrinolytic activity was also examined.. The fibrinolytic activities of conditioned medium and cell lysates from human glioma cell lines, A172, T98G, U87 and TM1 were studied by fibrin plate zymography. mRNA expression of tissue plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors (PAI-1, PAI-2) was measured by Northern blot analysis. PAF was added to the medium, and its effects on cell proliferation, fibrinolytic activity, mRNA expression of plasminogens and inhibitors were studied.. mRNA expression of plasminogens and inhibitors differed between individual cell lines. Only the medium and cell lysates from A172 cells revealed fibrinolytic activity. A172 cells showed mRNA expression of tPA. PAF at low concentrations, such as 1 nM, stimulated A172 cell proliferation, and high concentrations of PAF inhibited proliferation. PAF stimulated tPA release into the conditioned medium. mRNA expression of tPA was stimulated by low concentrations of PAF and inhibited by high concentrations.. The variability of mRNA expression of plasminogen activators (PAs) between different glioma cell lines may indicate that plasminogens and their inhibitors do not directly correlate with brain tumor growth. PAF may be an important factor in the local control of fibrinolytic activity in glioma and its proliferation.

Topics: Blotting, Northern; Brain Neoplasms; Cell Division; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Fibrin; Fibrinolysis; Gene Expression Regulation, Neoplastic; Glioma; Humans; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Platelet Activating Factor; RNA, Messenger; Tissue Plasminogen Activator; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

Hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) is a serine proteinase inhibitor that contains 2 Kunitz-domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI-2/PB in human gliomas in vivo and the effects of HAI-2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI-2/PB mRNA was expressed in normal brain and in low-grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI-2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG-1) were transiently transfected with an expression vector harboring human HAI-2/PB cDNA. Subsequent analysis indicated that the expression of HAI-2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI-2/PB inhibited Matrigel invasion of U251 and YKG-1 cells by 30% and 64%, respectively. This anti-invasive effect appeared to be mediated primarily by the inhibitory activity of HAI-2/PB against the serine proteinase-dependent matrix degradation. These findings suggest that the reduced expression of HAI-2/PB is possibly involved in the progression of human gliomas.

Topics: Astrocytoma; Blotting, Northern; Brain Neoplasms; Collagen; DNA Primers; Drug Combinations; Fibrin; Glioblastoma; Hepatocyte Growth Factor; Humans; Immunoblotting; Laminin; Membrane Glycoproteins; Neoplasm Invasiveness; Proteoglycans; Proto-Oncogene Proteins c-met; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Serine Endopeptidases; Serine Proteinase Inhibitors; Transfection; Trypsin Inhibitor, Kunitz Soybean

Extravascular, intratumoral fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumour growth. This is the first report on the presence and distribution of fibrinogen/fibrin in primary (14 glioblastomas) and metastatic (nine samples of lung cancer origin) human brain tumours detected by immunofluorescent techniques. All tissue samples showed specific staining for fibrinogen/fibrin. In glioblastomas fibrin deposits could be detected within and around tumour foci, while in metastatic brain tumours the tumour cell nodules were surrounded by fibrin deposits localized almost exclusively in the connective tissue compartment of tumours. Double-labelling reactions for von Willebrand factor and fibrinogen/fibrin has revealed that fibrin deposition occurred throughout the tumour stroma independently of tumour vasculature. The overlapping reactions for fibrinogen/fibrin and factor XIII subunit A, as well as the urea-insolubility of the deposits indicate the crosslinked, highly stabilized nature of fibrin both within and around tumours. Staining with Ki M7 monoclonal antibody specific for phagocytosing macrophages showed these cells to be scattered in the nonnecrotic areas in glioblastomas and to be accumulated at the interface of tumorous parenchyma and connective tissue in both primary and metastatic tumours. The close association between fibrin deposition and macrophage accumulation strongly suggests the active participation of tumour associated macrophages in the formation of stabilized intratumoral fibrin network in human brain neoplasms.

Topics: Blood Coagulation; Brain Neoplasms; Connective Tissue; Factor XIII; Fibrin; Fibrinolysis; Glioblastoma; Humans; Lung Neoplasms; Macrophages; Neoplasm Proteins

Malignant mesothelioma (MM) is a locally aggressive tumor that spreads by poorly understood mechanisms. Because neoplastic spread has been linked to altered fibrin turnover, we used immunohistochemistry of nine MM and three fibrous tumors of the pleura to confirm in vivo fibrin deposition and expression of selected coagulation and fibrinolytic reactants in MM. Tumor-associated fibrin was readily detectable at site of tissue invasion. Little fibrin was distributed within the tumor, but tissue factor and tissue factor pathway inhibitor, urokinase, urokinase receptor, and plasminogen activator inhibitors 1 and 2 were all detected in either epithelioid or sarcomatous areas of MM. We used the MS-1 human pleural mesothelioma cell line to determine how expression of these reactants is regulated. Fibrinolytic activity of MS-1 is mainly due to urokinase and is responsive to cytokine stimulation. Functional extrinsic activation and prothrombinase complexes assemble at the cell surface. MM express procoagulants as well as fibrinolytic reactants in vivo and in vitro that promote local fibrin formation and remodeling. Fibrin deposition occurs primarily at areas of tissue invasion and could promote local extension of this neoplasm. Sparsity of fibrin within the central portions of the tumor stroma suggests that local resorption of transitional fibrin occurs at sites of established MM.

Topics: Blood Coagulation; Blood Coagulation Factors; Brain Neoplasms; Cytokines; Fibrin; Fibrinolysis; Humans; Mesothelioma; Plasminogen Inactivators; Pleural Neoplasms; Tumor Cells, Cultured

Cell cultures were prepared from nine human brain tumors. Fibrin plate assays showed plasminogen-dependent fibrinolytic activity in lysates and in material released by these neoplastic cells but not in those from normal adult human white matter. Antibodies against human urokinase caused catalytic inhibition of the urokinase and of the plasminogen activator from WI-38 cells, simian virus 40-transformed WI-38 cells, human prostatic cells, and human ovarian carcinoma cells. However, the anti-urokinase immunoglobulin G did not inhibit the plasminogen activator activity of any of the human brain tumor preparations. These studies indicate that the plasminogen activator produced by human brain tumor cells is antigenically different from the plasminogen activator of other human normal and neoplastic cells.

Topics: Brain Chemistry; Brain Neoplasms; Cells, Cultured; Fibrin; Humans; Iodine Radioisotopes; Isoflurophate; Methods; Plasminogen; Plasminogen Activators; Urokinase-Type Plasminogen Activator

A case of an intracranial germinoma from the suprasellar region of a 9-year-old girl was examined in the electron microscope. The tumor consists, for the most part, of both large polygonal and small lymphocyte-like elements. Annulate lamellae are common in the epithelial cells. The small blood vessels are fenestrated, and the endothelial cells contain tubular bodies, membrane-bounded vacuoles containing dense fluid and occasional tubules, arrays of tubules within the nuclear envelope and rough endoplasmic reticulum, and a markedly irregular luminal surface. Dense, lamellated structures are present in the widened, collagen-containing perivascular spaces.

Topics: Brain Neoplasms; Capillaries; Cell Membrane; Cell Nucleus; Child; Dysgerminoma; Endoplasmic Reticulum; Endothelium; Epithelial Cells; Epithelium; Female; Fibrin; Humans; Inclusion Bodies; Lymphocytes; Vacuoles

Paired cerebrospinal fluid (CSF) and serum samples collected from 81 of 241 patients admitted to a district psychiatric hospital during a six month period were assayed for fibrin/fibrinogen degradation products (FDP) using a haemagglutination inhibition technique. FDP were found in all serum samples. Fifteen patients (18·5%) had FDP in the CSF (range 0·7-3·75 μg/ml.) and of these 13 (87%) had associated CSF protein abnormalities and 9 (60%) were hypertensive. Mean serum FDP values were the same (4·4 μg/ml.) in patients with and without FDP in the CSF. Three patients had raised serum FDP concentrations but no FDP in the CSF. The evidence suggests that the presence of FDP in CSF indicates recent central nervous system damage. In this series the most common cause was vascular disease.

Topics: Adult; Aged; Blood Pressure; Brain Diseases; Brain Neoplasms; Cerebrospinal Fluid Proteins; Cerebrovascular Disorders; Encephalitis; Female; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Intracranial Arteriosclerosis; Male; Middle Aged

Topics: Adenocarcinoma; Aged; Brain Neoplasms; Cell Transformation, Neoplastic; Diagnosis, Differential; Fibrin; Hemangiopericytoma; Hemangiosarcoma; Hemosiderin; Humans; Male; Meningioma; Neoplasm Metastasis; Neoplasm Regression, Spontaneous

Topics: Animals; Antigens; Brain Neoplasms; Carcinoma, Ehrlich Tumor; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glioblastoma; Glioma; Humans; Immunodiffusion; Immunoelectrophoresis; Iodine Isotopes; Meningioma; Mice; Neoplasms, Experimental; Plasminogen; Rabbits; Radiometry; Radionuclide Imaging; Rats; Sarcoma, Yoshida

Topics: Animals; Blood Coagulation; Brain Neoplasms; Carbon Tetrachloride Poisoning; Carcinoma 256, Walker; Female; Fibrin; Heart Neoplasms; In Vitro Techniques; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Mesentery; Neoplasm Metastasis; Neoplastic Cells, Circulating; Rats; Testicular Neoplasms; Wounds and Injuries

Topics: Animals; Antibodies; Brain Neoplasms; Fibrin; Humans; Iodine Isotopes; Neoplasms; Rabbits; Radioisotopes; Radionuclide Imaging

Topics: Brain Neoplasms; Cerebellar Neoplasms; Cerebrospinal Fluid; Cytodiagnosis; Equipment and Supplies; Fibrin; Medulloblastoma; Meningeal Neoplasms; Meningioma; Meningitis; Research; Specimen Handling

Topics: Brain Neoplasms; Diagnosis, Differential; Fibrin; Humans; Neoplasms