In vivo incorporation of [9,10-3H]-palmitate into a rat metastatic brain-tumor model

1991 ◽  
Vol 74 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Tadashi Nariai ◽  
Joseph J. DeGeorge ◽  
Nigel H. Greig ◽  
Stanley I. Rapoport
Keyword(s):  
Brain Tumor ◽  
Tumor Cell ◽  
Histological Study ◽  
Brain Slices ◽  
Tumor Model ◽  
Normal Brain ◽  
Intracerebral Injection ◽  
Content Type ◽  
Contralateral Normal Brain

✓ Lipid metabolism of an intracerebrally implanted brain tumor and normal brain was investigated in awake Fischer 344 rats using intravenously injected [9, 10-3H]-palmitate as a probe. A suspension of Walker 256 carcinosarcoma cells (250 cells in 5 µl medium), with or without 1 % low-melting-point agar, was implanted into the caudate nucleus of rats 8 to 9 weeks old. Control animals received an intracerebral injection without tumor cells. Seven days after implantation, awake rats were infused intravenously for 5 minutes with [9, 10-3H]-palmitate (6.4 mCi/kg). The rats were killed 20 minutes after initiation of the infusion and coronal brain slices were obtained for quantitative autoradiography and light histological study. Tumor cell masses were histologically well demarcated from the surrounding brain tissue. Tumor tissue incorporation of [9, 10-3H]- palmitate was heterogeneous, ranging on average from 3.1- to 6.1-fold greater than in the corresponding contralateral brain. In addition, incorporation corresponded to regional tumor cell density. The incorporation rate constant of [9, 10-3H]-palmitate in tumor was significantly increased compared to control brain and was independent of tumor size. Necrotic areas within tumors showed no incorporation of radiolabeled palmitate. Brain surrounding the tumors and control injection sites showed reactive gliosis, and possessed 30% greater incorporation of [9, 10-3H]-palmitate than contralateral normal brain. These results suggest that [9, 10-3H]- palmitate can be used to image brain tumors in vivo, measuring turnover and/or synthesis of tumor and brain lipid.

Evaluation of Poly (Glycerol-Adipate) Nanoparticle Uptake in an In Vitro 3-D Brain Tumor Co-Culture Model

2007 ◽  
Vol 232 (8) ◽  
pp. 1100-1108 ◽  
Author(s):  
W. Meng ◽  
P. Kallinteri ◽  
D. A. Walker ◽  
T. L. Parker ◽  
M. C. Garnett
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Single Cells ◽  
Brain Slices ◽  
Brain Cells ◽  
Normal Brain ◽  
New Model ◽  
Culture Model

Despite the inherent problems associated with in vivo animal models of tumor growth and metastases, many of the current in vitro brain tumor models also do not accurately mimic tumor-host brain interactions. Therefore, there is a need to develop such co-culture models to study tumor biology and, importantly, the efficacy of drug delivery systems targeting the brain. So far, few investigations of this nature have been published. In this paper we describe the development of a new model system and its application to drug delivery assessment. For our new model, a co-culture of DAOY cell brain tumor aggregates and organo-typic brain slices was developed. Initially, the DAOY aggregates attached to cerebellum slices and invaded as a unit. Single cells in the periphery of the aggregate detached from the DAOY aggregates and gradually replaced normal brain cells. This invasive behavior of DAOY cells toward organotypic cerebellum slices shows a similar pattern to that seen in vivo. After validation of the co-culture model using transmission electron microscopy, nanoparticle (NP) uptake was then evaluated. Confocal micrographs illustrated that DAOY cells in this co-culture model took up most of the NPs, but few NPs were distributed into brain cells. This finding corresponded with results of NP uptake in DAOY and brain aggregates reported elsewhere.

Distribution of hematoporphyrin derivative in the rat 9L gliosarcoma brain tumor analyzed by digital video fluorescence microscopy

1984 ◽  
Vol 61 (6) ◽  
pp. 1113-1119 ◽  
Author(s):  
James E. Boggan ◽  
Robert Walter ◽  
Michael S. B. Edwards ◽  
Janis K. Borcich ◽  
Richard L. Davis ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Model ◽  
Normal Brain ◽  
Hematoporphyrin Derivative ◽  
Content Type ◽  
9L Gliosarcoma ◽  
Video Fluorescence Microscopy ◽  
Brain Tumor Model ◽  
The Brain ◽  
Fine Print

✓ A digital video fluorescence microscopy technique was used to evaluate the distribution of hematoporphyrin derivative (HPD) in the rat intracerebral 9L gliosarcoma brain-tumor model at 4, 24, 48, and 72 hours after intravenous administration of 10 mg/kg of the drug. Compared to surrounding normal brain, there was significant preferential uptake of HPD into the tumor. In sections surveyed, fluorescence reached a maximum value by 24 hours; however, only 33% to 44% of the tumor was fluorescent. In contrast, fluorescence within the surrounding normal brain was maximum at 4 hours, but was present in less than 1% of the brain tissue evaluated. The effect of HPD sensitization to a laser light dose (633 nm) of 30 joules/sq cm delivered through the intact skull was evaluated histologically in 10 rats. A patchy coagulation necrosis, possibly corresponding to the distribution of HPD fluorescence seen within the tumor, was observed. There was evidence that photoradiation therapy (PRT) affects defective tumor vasculature and that a direct tumor cell toxicity spared normal brain tissue. Despite these findings, limited uptake of HPD in tumor and the brain adjacent to tumor may decrease the effectiveness of PRT in the 9L gliosarcoma brain-tumor model. Because of the similarity between the capillary system of the 9L tumor and human brain tumors, PRT may have a limited therapeutic effect in patients with malignant brain tumors.

Invasion of human glioma biopsy specimens in cultures of rodent brain slices: a quantitative analysis

2002 ◽  
Vol 97 (1) ◽  
pp. 169-176 ◽  
Author(s):  
Sophie de Boüard ◽  
Christo Christov ◽  
Jean-Sébastien Guillamo ◽  
Lina Kassar-Duchossoy ◽  
Stéphane Palfi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Brain Slices ◽  
Lower Grade ◽  
Human Glioma ◽  
Newborn Mice ◽  
Content Type ◽  
Biopsy Specimens ◽  
Rodent Brain ◽  
Fine Print

Object. The reliable assessment of the invasiveness of gliomas in vitro has proved elusive, because most invasion assays inadequately model in vivo invasion in its complexity. Recently, organotypical brain cultures were successfully used in short-term invasion studies on glioma cell lines. In this paper the authors report that the invasiveness of human glioma biopsy specimens directly implanted into rodent brain slices by using the intraslice implantation system (ISIS) can be quantified with precision. The model was first validated by the demonstration that, in long-term studies, established glioma cells survive in the ISIS and follow pathways of invasion similar to those in vivo. Methods. Brain slices (400 µm thick) from newborn mice were maintained on millicell membranes for 15 days. Cells from two human and one rodent glioblastoma multiforme (GBM) cell lines injected into the ISIS were detected by immunohistochemistry or after transfection with green fluorescent protein—containing vectors. Preferential migration along blood vessels was identified using confocal and fluorescent microscopy. Freshly isolated (≤ 24 hours after removal) 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate—prelabeled human glioma biopsy specimens were successfully implanted in 19 (83%) of 23 cases, including 12 GBMs and seven lower grade gliomas (LGGs). Morphometric quantification of distance and density of tumor cell invasion showed that the GBMs were two to four times more invasive than the LGGs. Heterogeneity of invasion was also observed among GBMs and LGGs. Directly implanted glioma fragments were more invasive than spheroids derived from the same biopsy specimen. Conclusions. The ISIS combines a high success rate, technical simplicity, and detailed quantitative measurements and may, therefore, be used to study the invasiveness of biopsy specimens of gliomas of different grades.

Quantitative Measurements of Regional Glucose Utilization and Rate of Valine Incorporation into Proteins by Double-Tracer Autoradiography in the Rat Brain Tumor Model

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto
Keyword(s):  
Protein Synthesis ◽  
Brain Tumor ◽  
Rat Brain ◽  
Brain Tissue ◽  
Glucose Utilization ◽  
Tumor Model ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Rat Brain Tumor ◽  
Brain Tumor Model

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.

Immunosuppression by phenytoin: implication for altered immune competence in brain-tumor patients

1984 ◽  
Vol 61 (6) ◽  
pp. 1085-1090 ◽  
Author(s):  
Kenji Kikuchi ◽  
Christopher I. McCormick ◽  
Edward A. Neuwelt
Keyword(s):  
Brain Tumor ◽  
Culture Medium ◽  
Thymidine Incorporation ◽  
Pokeweed Mitogen ◽  
Immune Competence ◽  
Lymphocyte Function ◽  
Tumor Patients ◽  
Content Type ◽  
Anticonvulsant Agent

✓ This investigation was conducted to examine the immunosuppressive potential of phenytoin in vivo and to document a correlation between phenytoin therapy and depressed lymphocyte responsiveness to mitogens. It was thought that phenytoin, the most widely used anticonvulsant agent, may play some role in the immunosuppression seen in brain-tumor patients. The effect of phenytoin on mitogen-stimulated lymphocyte function was evaluated by tritiated (3H)-thymidine incorporation and lymphocyte nuclear size distribution. Lymphocytes from either phenytoin-treated or normal rabbits were incubated for 90 hours in culture medium in the presence of three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Significant suppression of mitogen-induced activation of the lymphocytes from treated animals was demonstrated. The present studies suggest a possible connection between phenytoin therapy and altered immune competence in brain-tumor patients.

Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo

2005 ◽  
Vol 13 (6) ◽  
pp. 337-343 ◽  
Author(s):  
Bhawna Gupta ◽  
Tatiana S. Levchenko ◽  
Dmitry A. Mongayt ◽  
Vladimir P. Torchilin
Keyword(s):  
Monoclonal Antibody ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Tumor Model ◽  
Subcutaneous Tumor ◽  
Brain Tumor Cells

scholarly journals Analysis of Fluorescence Decay Kinetics of Indocyanine Green Monomers and Aggregates in Brain Tumor Model In Vivo

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3185
Author(s):  
Dina Farrakhova ◽  
Igor Romanishkin ◽  
Yuliya Maklygina ◽  
Lina Bezdetnaya ◽  
Victor Loschenov
Keyword(s):  
Brain Tumor ◽  
Indocyanine Green ◽  
Fluorescence Lifetime ◽  
Tumor Model ◽  
Fluorescence Decay ◽  
Decay Kinetics ◽  
Lifetime Analysis ◽  
Fluorescence Decay Kinetics ◽  
Brain Tumor Model

Spectroscopic approach with fluorescence time resolution allows one to determine the state of a brain tumor and its microenvironment via changes in the fluorescent dye’s fluorescence lifetime. Indocyanine green (ICG) is an acknowledged infra-red fluorescent dye that self-assembles into stable aggregate forms (ICG NPs). ICG NPs aggregates have a tendency to accumulate in the tumor with a maximum accumulation at 24 h after systemic administration, enabling extended intraoperative diagnostic. Fluorescence lifetime analysis of ICG and ICG NPs demonstrates different values for ICG monomers and H-aggregates, indicating promising suitability for fluorescent diagnostics of brain tumors due to their affinity to tumor cells and stability in biological tissue.

Localized 31P magnetic resonance spectroscopy of large pediatric brain tumors

1990 ◽  
Vol 72 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Leslie N. Sutton ◽  
Robert E. Lenkinski ◽  
Bruce H. Cohen ◽  
Roger J. Packer ◽  
Robert A. Zimmerman
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Tumors ◽  
Malignant Tumors ◽  
Benign Tumors ◽  
Resonance Spectroscopy ◽  
Normal Brain ◽  
Content Type ◽  
Metabolic Fingerprint

✓ Fourteen children aged 1 week to 16 years, with a variety of large or superficial brain tumors, underwent localized in vivo 31P magnetic resonance spectroscopy of their tumor. Quantitative spectral analysis was performed by measuring the area under individual peaks using a computer algorithm. In eight patients with histologically benign tumors the spectra were considered to be qualitatively indistinguishable from normal brain. The phosphocreatine/inorganic phosphate ratio (PCr/Pi) averaged 2.0. Five patients had histologically malignant tumors; qualitatively, four of these were considered to have abnormal spectra, showing a decrease in the PCr peak. The PCr/Pi ratio for this group averaged 0.85, which was significantly lower than that seen in the benign tumor group (p < 0.05). No difference between the two groups was seen in adenosine triphosphate or phosphomonoesters. It is concluded that a specific metabolic “fingerprint” for childhood brain tumors may not exist, but that some malignant tumors show a pattern suggestive of ischemia.

Effect of pentobarbital on normal brain protection and on the response of 9L rat brain tumor to radiation therapy

1993 ◽  
Vol 79 (4) ◽  
pp. 577-583 ◽  
Author(s):  
Bruce F. Kimler ◽  
Changnian Liu ◽  
Richard G. Evans ◽  
Robert A. Morantz
Keyword(s):  
Radiation Therapy ◽  
Brain Tumor ◽  
Rat Brain ◽  
Tumor Model ◽  
Intracranial Tumor ◽  
Normal Brain ◽  
Animal Survival ◽  
Significant Difference ◽  
Rat Brain Tumor ◽  
Brain Tumor Model

✓ The authors attempted to confirm published reports that pentobarbital protects against radiation-induced damage to normal rat brain, as well as enhances radiotherapeutic efficacy in a rat brain tumor model. They evaluated animal survival in 9L gliosarcoma-burdened rats that received whole-brain radiation therapy (16, 24, 32, or 40 Gy) while under intraperitoneal pentobarbital (60 mg/kg) or intramuscular ketamine (60 mg/kg) sedation. The animals were examined at autopsy to attribute death to either intracranial tumor growth or normal brain toxicity in the absence of discernible tumor. There was no difference between the two anesthesia groups regarding the survival of unirradiated animals. Radiation therapy produced a significant dose-dependent prolongation in animal survival, which was limited by the development of normal tissue toxicity at the higher doses. When compared to ketamine anesthesia, pentobarbital anesthesia appeared to offer some protection (not statistically significant) against early (but not late) toxicity at selected radiation doses. A reduction in the number of deaths from tissue toxicity suggested an increased antitumor effect, but again this was not statistically significant. Only in one case was there even a marginal significant difference (p = 0.045) between overall therapeutic efficacy in rats sedated with pentobarbital versus ketamine. While there may be a radioprotective effect of pentobarbital in rat brains without intracranial tumor, there is no conclusive evidence for either radioprotection or significant improvement of radiotherapeutic efficacy in this 9L rat brain tumor model.

18F-fluoro-2′-deoxyuridine as a tracer of nucleic acid metabolism in brain tumors

1990 ◽  
Vol 72 (1) ◽  
pp. 110-113 ◽  
Author(s):  
Yuji Tsurumi ◽  
Motonobu Kameyama ◽  
Kiichi Ishiwata ◽  
Ryuichi Katakura ◽  
Minoru Monma ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Nucleic Acid ◽  
Tumor Tissue ◽  
Acid Metabolism ◽  
Tumor Model ◽  
Nucleic Acid Metabolism ◽  
Content Type ◽  
Positron Emission ◽  
Rat Brain Tumor ◽  
Notable Increase

✓ The value of 18F-fluoro-2′-deoxyuridine (18F-FUdR) as a tracer for nucleic acid metabolism was studied using an experimental rat brain-tumor model. The 18F activity in the tumor tissue 45 minutes after intravenous injection of 18F-FUdR was about 12 times higher than that in the contralateral cortex. Double-labeled autoradiography with 18F-FUdR and 14C-thymidine revealed similar brain-tumor images. In contrast, an autoradiographic comparison of 18F-FUdR with 14C-aminoisobutyric acid, which reveals the impairment of the blood-brain barrier, showed very different images. Also, the 18F radioactivity in the tumor tissue was at a constant level for 30 to 120 minutes, whereas a notable increase in 18F activity with time was observed in nucleotides and acid-insoluble fractions. These results suggest that the distribution pattern of 18F-FUdR closely correlates with the metabolism of nucleic acid and that this drug could be a useful tracer for positron emission tomography.

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