RESUMEN
UNLABELLED: The PET imaging properties of three phenyltropane drugs with differing affinities and selectivities for the dopamine over serotonin transporter, were compared. METHODS: Carbon-11-CFT (WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), 11C-CCT (RTI-131, 2 beta-carbomethoxy-3 beta-(4-monochlorophenyl)tropane), and 11C-CDCT (dichloropane, 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane) were evaluated as imaging probes for dopamine neurons in five normal and in two MPTP-treated cynomolgus monkeys (macaca fascicularis) using a high-resolution PET imaging system (PCR-I). RESULTS: For 11C-CFT, the specific binding ratio (as defined by the ratio of radioactivity levels in striatum versus cerebellum) was 4.2 +/- 0.8 in caudate and 4.9 +/- 1.2 in putamen at 60 min and 4.9 +/- 1.2 and 5.5 +/- 1.1 at 90 min in control animals. In MPTP-treated monkeys the corresponding ratios were 1.4 +/- 0.1 in caudate and 1.5 +/- 0.1 in putamen at 60 min and 1.3 +/- 0.1 in caudate and 1.4 +/- 0.3 in putamen at 90 min. For the monochloro analog of CFT, 11C-CCT, the ratios in control caudate and putamen were 2.7 +/- 0.4 and 3.4 +/- 0.3, respectively, at 60 min and 3.7 +/- 0.5 and 4.4 +/- 0.6, respectively, at 90 min. In MPTP-treated animals, corresponding ratios were 1.4 +/- 0.4 and 1.5 +/- 0.3 at 60 min and 1.4 +/- 0.4 and 1.6 +/- 0.4 at 90 min. The dichloro analog of CFT, CDCT, which has the highest affinity for the dopamine transporter, generated the lowest ratios in control brains, 2.3 +/- 0.4 in caudate and 2.4 +/- 0.5 in putamen at 60 min. In one MPTP-treated monkey, the corresponding ratios were 1.6 +/- 0.4 and 1.8 +/- 0.3. In comparison with 11C-CFT, both 11C-CCT and 11C-CDCT were less selective and had high uptake in the thalamus. CONCLUSION: The present results clearly indicate that 11C-CFT is a useful ligand for monitoring dopamine neuronal degeneration.
Asunto(s)
Encéfalo/diagnóstico por imagen , Inhibidores de Captación de Dopamina , Dopamina/metabolismo , Terminaciones Nerviosas/química , Enfermedad de Parkinson Secundaria/diagnóstico por imagen , Tomografía Computarizada de Emisión , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Radioisótopos de Carbono , Cocaína/análogos & derivados , Femenino , Macaca fascicularis , Masculino , Terminaciones Nerviosas/diagnóstico por imagen , Enfermedad de Parkinson Secundaria/inducido químicamenteRESUMEN
Positron emission tomography (PET) may provide an ideal means of monitoring the delivery of cells to normal and pathological tissue owing to its high resolution, specificity and three dimensional imaging capabilities. In order to implement such a technique, it is important to develop a labeling method for cells which provides a rapid and stable incorporation of the positron emitter without altering the viability or functional activity of the cells to be studied. Two approaches have been explored to achieve this end: metabolic incorporation of 2-[18F]fluorodeoxyglucose (2-[18F]FDG) or protein labeling with [11C]methyl iodide (MI). IL-2 activated mouse natural killer lymphocytes were expanded in culture for 7 days and used for these studies. Uptake of 2-[18F]FDG by the natural killer cells was found to occur rapidly and to level off after 30 min. The amount of cell-associated label was found to decay at a steady rate immediately following the procedure, with approximately 21% loss of label after 1 h. In contrast, labeling of cells with MI provided a stable association for 60 min which did not alter the viability or the cytotoxic activity of the cells. Injection of the labeled cells into a normal mouse followed by a full body scanning procedure demonstrated the accumulation of the cells in the lungs which corresponded to those seen by microscopy. These findings suggest that labeling lymphocyte populations with MI may provide a rapid and practical means to quantify systemic cell distribution by PET.
Asunto(s)
Radioisótopos de Carbono , Radioisótopos de Flúor , Marcaje Isotópico/métodos , Tomografía Computarizada de Emisión/métodos , Animales , Citotoxicidad Inmunológica , Desoxiglucosa/análogos & derivados , Fluorodesoxiglucosa F18 , Hidrocarburos Yodados , Células Asesinas Naturales/inmunología , RatonesRESUMEN
We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease.
Asunto(s)
Radioisótopos de Carbono , Núcleo Caudado/diagnóstico por imagen , Cocaína/análogos & derivados , Dopamina/metabolismo , Actividad Motora , Enfermedad de Parkinson Secundaria/diagnóstico por imagen , Putamen/diagnóstico por imagen , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Núcleo Caudado/patología , Núcleo Caudado/fisiopatología , Cocaína/metabolismo , Cocaína/farmacocinética , Dopamina/análisis , Terminaciones Nerviosas/diagnóstico por imagen , Terminaciones Nerviosas/patología , Enfermedad de Parkinson Secundaria/patología , Enfermedad de Parkinson Secundaria/fisiopatología , Putamen/patología , Putamen/fisiopatología , Tomografía Computarizada de Emisión/métodosRESUMEN
In vivo physiological changes associated with striatal pathology were determined by measurement of glucose utilization, binding to D1 receptors and dopamine reuptake sites, regional blood flow, and behavior before and after unilateral quinolinate infusions into caudate-putamen in three nonhuman primates (Macaca fascicularis and Macaca mulatta). Following the quinolinate lesion, symptoms similar to those of Huntington's disease could be induced by dopamine agonist treatment. In addition, all animals showed a long-term decrease in glucose utilization in the caudate by [19F]fluoro-2-deoxy-D-glucose positron emission tomography (PET). At 4-6 weeks following the lesion the average decrease in glucose utilization in the caudate-putamen was between 40 and 50% of the prelesion values in primates with large lesions. Corresponding caudate-putamen regional blood volume in these animals showed a 61 and 74% decrease as studied by magnetic resonance imaging with somewhat smaller changes observed in an index of cerebral blood flow. The caudate-putamen uptake rate constants for D1 receptors reflected neuronal loss and decreased by an average 40 and 48%, as determined by 11C-labeled Schering compound (SCH 39 166) and PET. Dopamine reuptake sites and fibers assessed by the 11C-labeled cocaine analog, WIN 35 428 compound, and PET showed a temporary decrease in areas with mild neuronal loss and a long-term decrease in striatal regions with severe destruction. These results, which were consistent with behavioral changes and neuropathology seen at postmortem examination, can be related to in vivo physiological studies of Huntington's disease patients.
Asunto(s)
Núcleo Caudado/fisiología , Glucosa/metabolismo , Hemodinámica , Imagen por Resonancia Magnética , Putamen/fisiología , Receptores Dopaminérgicos/metabolismo , Tomografía Computarizada de Emisión , Acetilcolinesterasa/metabolismo , Animales , Apomorfina/farmacología , Conducta Animal/efectos de los fármacos , Núcleo Caudado/efectos de los fármacos , Núcleo Caudado/patología , Dopamina/metabolismo , Macaca fascicularis , Macaca mulatta , Trastornos del Movimiento/etiología , Terminaciones Nerviosas/metabolismo , Putamen/efectos de los fármacos , Putamen/patología , Ácido Quinolínico/farmacología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Optimal delivery of immunologically active cells to target tissue(s) is important for improving adoptive immunotherapy of neoplastic diseases. By using positron emission tomography, we have measured the systemic distribution and tumor localization of locally injected, activated natural killer (NK) cells or nonactivated lymphocytes in the FSaII fibrosarcoma grown s.c. in the tail of C3H mice. Murine NK cells were isolated and expanded in the presence of interleukin 2 and collected at 5 to 7 days after culture. These cells were then washed and labeled with [11C]methyl iodide, a positron-emitting isotope. Ten million activated or nonactivated cells were injected into the lateral tail vein distal to the tumor over a period of 2 min, and the accumulation of counts in the tumor was monitored during the injection and at 30-60 min postinjection. There was no significant difference in the rate of accumulation of activated NK cells (685 +/- 264 (SE); n = 5) versus nonactivated splenic lymphocytes (595 +/- 105; n = 5) during the injection period. Whole body scans of the mice done at 30 min to 1 h postinjection showed that the number of activated cells retained within the tumor ranged from 4 to 30% (15.3 +/- 4.9%; n = 5) of the injected dose. Activated NK cells which were not retained by the tumor accumulated in the lungs, liver, and spleen. In contrast, from 3 to 4% (3.4 +/- 0.2%; n = 5) of nonactivated lymphocytes remained within the tumor by 1 h. Nonactivated cells were distributed more homogeneously throughout the systemic circulation than the activated cells, although these cells also demonstrated increased retention in the lungs, liver, and spleen. The present study demonstrates that positron emission tomography may be used to quantify the number of effector cells which accumulate within tumors and to determine their biodistribution. The retention of labeled cells within the tumor may also be used as a means of imaging the tumor. Finally, the preferential accumulation of effector cells in the tumor vasculature following local injection has useful implications for adoptive immunotherapy.
Asunto(s)
Inmunoterapia Adoptiva , Células Asesinas Naturales/diagnóstico por imagen , Sarcoma Experimental/diagnóstico por imagen , Animales , Radioisótopos de Carbono , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos C3H , Sarcoma Experimental/inmunología , Sarcoma Experimental/terapia , Tomografía Computarizada de EmisiónRESUMEN
Neutron capture therapy has a promising role in cancer treatment since it can achieve selectivity at the cellular level. The effect of this therapy depends on the subcellular localization of boron atoms in the target cell. Five boron compounds were investigated in this study: the monomeric and dimeric sulfhydryl boranes (BSH and BSSB), a boronated phenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). The study shows that when exponentially growing rat 9L gliosarcoma cells are exposed to an isoeffective concentration of each of the five compounds for 1 h, BOPP produces a much higher intracellular level of boron than the other four compounds; BSSB produces the second highest level, while exposure to BSH, VCDP, and BPA resulted in lower intracellular boron levels. Subcellular fractionation studies showed that most of the boron localized in the cytoplasm of the cells with all five compounds. A significantly higher boron concentration was found in the lysosomes of the cells, but the nuclei contained only minimal concentrations of boron. Computer simulations of neutron capture reactions with boron using a Monte Carlo simulation code indicated that BOPP would yield the highest potential effectiveness, followed by BSSB, BSH, VCDP, and BPA, in that order.
Asunto(s)
Compuestos de Boro/farmacocinética , Terapia por Captura de Neutrón de Boro , Glioma/metabolismo , Fracciones Subcelulares/metabolismo , Animales , Simulación por Computador , Método de Montecarlo , RatasRESUMEN
The neutron capture reaction in boron (10B(n, alpha)7Li) generates two short-range particles with high linear energy transfer. The effect of neutron capture therapy depends on the selective localization of 10B atoms in target cells. The determination of the distribution of boron compounds in cancer cells at the subcellular level is required for the understanding of the effect of this treatment. The monomeric sulfhydryl borane (BSH) compound has been used clinically in Japan and preclinically in the U.S.A. Recently, new compounds have been developed: a dimeric sulfhydryl borane (BSSB), a boronophenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). This study demonstrates that the porphyrin complexes (BOPP and VCDP) are more cytotoxic than the other three compounds to the rat 9L gliosarcoma cell line. Using atomic absorption spectrophotometry to determine boron content for cellular uptake studies of these agents, we found that of the five compounds tested BOPP (25 microM) exposure resulted in the greatest boron uptake averaging 305 ng B/10(6) cells. BSSB (500 microM) was second averaging 93 ng B/10(6) cells, BSH (500 microM) third averaging 62 ng B/10(6) cells, VCDP (25 microM) fourth averaging 58 ng B/10(6) cells, and BPA (500 microM) fifth averaging 7.4 ng B/10(6) cells. Data on the distribution of boron in the nuclei, mitochondria, lysosomes, microsomes, and cytosomes of 9L cells are also presented.
Asunto(s)
Compuestos de Boro/metabolismo , Terapia por Captura de Neutrón de Boro , Animales , Borohidruros/metabolismo , Compuestos de Boro/farmacología , Supervivencia Celular , Isótopos , Fenilalanina/análogos & derivados , Fenilalanina/metabolismo , Radioquímica , Espectrofotometría Atómica , Fracciones Subcelulares/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Sulfuros/metabolismo , Células Tumorales Cultivadas/metabolismoRESUMEN
Monkeys were treated on two regimens of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections to achieve dopamine fiber degeneration of differing severities. A rapid treatment regimen produced a severe parkinsonian syndrome, whereas an intermittent regimen did not cause locomotor symptoms to appear up to 25 weeks. High resolution PET scanning of dopamine nerve terminals revealed that the specific binding of the dopamine transporter [11C]-WIN 35,428 ([11C]-CFT) was diminished by 94% (caudate nucleus) and by 93% (putamen) in the symptomatic monkey. Decreases of 65 and 67% were detected in these regions in the non-symptomatic monkey. Post-mortem immunocytochemical evaluation of presumed dopamine fibers by tyrosine-hydroxylase showed similar reductions in the symptomatic animal.
Asunto(s)
Cocaína/análogos & derivados , Dopamina/análisis , Fibras Nerviosas/química , Enfermedad de Parkinson Secundaria/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Cocaína/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Macaca fascicularis , Actividad Motora/efectos de los fármacos , Fibras Nerviosas/diagnóstico por imagen , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/diagnóstico por imagen , Ensayo de Unión Radioligante , Tomografía Computarizada de EmisiónRESUMEN
The effect of positron range on the image-plane resolution of tomographic images is evaluated through calculations based on a model which employs beta-decay energy spectra and an empirical range formula. Predicted range distribution functions are compared with published measurements for three medically important positron emitters: (11 )C, (68)Ga, and (82)Rb. The effect of tomographic slice thickness on point-source annihilation distribution functions is also demonstrated. Line-spread functions are calculated using the model, for the above isotopes as well as for (18)F, (15)O, and (13)N. Image-plane resolution predictions are made for high-resolution positron cameras for various positron emitting isotopes with end-point energies up to 4 MeV.
RESUMEN
In this article, we show that 1) computed tomographic (CT)-guided stereotactic infusion of an excitotoxin into the striatum of a nonhuman primate provides a useful neuropathologic and behavioral model for Huntington's disease. 2) High-resolution positron emission tomography (PET) can be used to image the decreased glucose utilization and the preservation of dopaminergic terminals in the lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2-beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of cross-species striatal fetal tissue into the lesioned caudate-putamen reduces many of the abnormal motor movements and behavioral changes seen in the Huntington's disease primate model. 4) Graft rejection results in the return of the abnormal signs of the pregrafted state. These results indicate that treatment of the neuronal deficit in Huntington's disease can involve intervention at the local neuronal circuit level. CT-guided stereotactic implantation of cells that might protect or replace this defective circuitry may eventually provide an effective treatment for Huntington's disease.
Asunto(s)
Trasplante de Tejido Encefálico , Núcleo Caudado/patología , Trasplante de Tejido Fetal , Enfermedad de Huntington/cirugía , Putamen/patología , Animales , Apomorfina/farmacología , Trasplante de Tejido Encefálico/fisiología , Radioisótopos de Carbono , Cocaína/análogos & derivados , Cocaína/metabolismo , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Trasplante de Tejido Fetal/fisiología , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Supervivencia de Injerto , Enfermedad de Huntington/diagnóstico por imagen , Ácido Iboténico , Masculino , Actividad Motora/efectos de los fármacos , Neurotoxinas , Papio , Ácido Quinolínico , Ratas , Técnicas Estereotáxicas , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos X , Trasplante HeterólogoRESUMEN
Positron emission tomography (PET) and MR have been compared with histochemical pathology to show affected tissue areas in rat brain after right middle cerebral artery (MCA) occlusion combined with temporary bilateral common carotid artery occlusion in Long Evans rats. The glucose metabolic rate was 65 +/- 8 mumol/100 ml/min in the right cortical gray matter corresponding to the occluded middle cerebral artery territory and 93 +/- 8 mumol/100 ml/min in the corresponding (left) normal side. Infarcted tissue showed decreased PET activity and increased signal in MR T2-weighted scans ipsilateral to the MCA occlusion. These regions correspond to a zone of focal infarction identified in coronal tissue sections stained with 3-4-5 triphenyl tetrazolium chloride. This study demonstrates that PET can be used to study glucose utilization in rat stroke model in vivo and noninvasively.
Asunto(s)
Isquemia Encefálica/diagnóstico , Imagen por Resonancia Magnética , Tomografía Computarizada de Emisión , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Simulación por Computador , Glucosa/metabolismo , Masculino , Mitocondrias/enzimología , Oxidorreductasas/metabolismo , RatasRESUMEN
Glucose utilization studies using high resolution positron emission tomography and tissue oxygenation measurements using microelectrode techniques were carried out in nude mice bearing oncogene-transformed (Rat1pEJ6.6 and REFpneoMYCrasEpool) cell line tumours and a non-transformed (Rat1) cell line tumour to determine the correlation between glucose utilization, tissue oxygenation and tumour growth rate. Control measurements were performed in the subcutis of tumour-free animals. Accelerated growth rates were observed in both ras-transformed cell lines with tumour doubling times of 2.5-4 days while Rat1 tumours had a doubling time of 28 days. Since rapid growth rates necessitate elevated consumption of oxygen and nutrients, severe tumour hypoxia was observed in tumours from both ras-transformed cell lines; median pO2 being 1-5 mmHg (tumour sizes ca. 400 mm3). Size-matched Rat1 tumours exhibited a median pO2 value of 12 mmHg corresponding to the slow growth rate. Comparing both ras-transformed cell lines, Rat1pEJ6.6 tumours had a more adequate vascularization than REFpneoMYCrasEpool tumours indicated by a better tissue oxygenation (5 mmHg versus 1 mmHg) and higher glucose metabolic rates (13.4 +/- 2.2 mumol/min/100 cm3 versus 9.7 +/- 1.3 mumol/min/100 cm3). At advanced growth stages, a reduction of tissue oxygen levels is obtained which is accompanied by a 30% elevation of glucose metabolic rate. The data presented here demonstrate for the first time an impact of well defined oncogenic alterations on the therapeutically relevant parameters of the micromilieu of malignant tumours.
Asunto(s)
Línea Celular Transformada/metabolismo , Glucosa/metabolismo , Consumo de Oxígeno , Animales , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Fluorodesoxiglucosa F18 , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Oncogenes , Factores de Tiempo , Tomografía Computarizada de EmisiónRESUMEN
A Monte Carlo simulation study has been carried out to investigate the suitability of neutron beams of various energies for therapeutic efficacy in boron neutron capture therapy. The dosimetric properties of unidirectional, monoenergetic neutron beams of varying diameters in two different phantoms (a right-circular cylinder and an ellipsoid) made of brain-equivalent material were examined. The source diameter was varied from 0.0 to 20.0 cm; neutron energies ranged from 0.025 eV up to 800 keV, the maximum neutron energy generated by a tandem cascade accelerator using 2.5-MeV protons in a 7Li(p,n)7Be reaction. Such a device is currently under investigation for use as a neutron source for boron neutron capture therapy. The simulation studies indicate that the maximum effective treatment depth (advantage depth) in the brain is 10.0 cm and is obtainable with a 10-keV neutron beam. A useful range of energies, defined as those neutron energies capable of effectively treating to a depth of 7 cm in brain tissue, is found to be 4.0 eV to 40.0 keV. Beam size is shown not to affect advantage depth as long as the entire phantom volume is used in determining this depth. Dose distribution in directions parallel to and perpendicular to the beam direction are shown to illustrate this phenomenon graphically as well as to illustrate the differences in advantage depth and advantage ratio and the contribution of individual dose components to tumor dose caused by the geometric differences in phantom shape.
Asunto(s)
Boro , Neoplasias/radioterapia , Neutrones , Neoplasias Encefálicas/radioterapia , Simulación por Computador , Humanos , Isótopos , Modelos Estructurales , Método de Montecarlo , Dosificación RadioterapéuticaAsunto(s)
Compuestos de Boro/uso terapéutico , Neutrones/uso terapéutico , Aceleradores de Partículas/instrumentación , Fenómenos Biofísicos , Biofisica , Neoplasias Encefálicas/radioterapia , Arquitectura y Construcción de Instituciones de Salud , Humanos , Isótopos , Modelos Estructurales , Protones , Dosificación RadioterapéuticaRESUMEN
[11C]-1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ([11C]MPTP), a compound producing parkinson-like symptoms in several species, has been synthesized and purified in sufficient activity to obtain tomographic images in the monkey. Biodistribution data has also been obtained in rats. Carbon-11-labeled MPTP could be used as a probe to study the pharmacokinetics of the compound under various research conditions in animals. Because of its neurotoxicity, the compound is not intended for use in humans.
Asunto(s)
Radioisótopos de Carbono , Enfermedad de Parkinson/diagnóstico por imagen , Piridinas , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Macaca nemestrina , Piridinas/metabolismo , Cintigrafía , Ratas , Distribución TisularRESUMEN
N-[11C-methyl]chlorphentermine ([11C]NMCP) and N,N-[11C-dimethyl]chlorphentermine ([11C]NDMCP) were prepared from chlorphentermine and 11CH3I in DMF and evaluated in rats as brain blood-flow agents for positron emission tomography (PET). Tissue distribution of [11C]NMCP showed that brain uptake was 2.70 +/- 0.40% of injected dose per organ at 5 min with no change in radioactivity concentration up to 30 min after i.v. injection. Approximately 80% of the initial brain uptake remained at 60 min. On the other hand, initial brain uptake of [11C] NDMCP (3.66 +/- 0.31 and 3.63 +/- 0.88% injected dose per organ at 5 and 15 min, respectively) was greater than that of [11C]NMCP. The brain activity however, rapidly decreased to 2.38 +/- 0.17 and 1.82 +/- 0.32% at 30 and 60 min, respectively. Because of its longer retention in the brain compared with [11C]NDMCP, [11C]NMCP would be a potential brain blood-flow agent for quantitative PET studies.
Asunto(s)
Circulación Cerebrovascular , Clorfentermina/análogos & derivados , Fentermina/análogos & derivados , Tomografía Computarizada de Emisión/métodos , Animales , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono , Clorfentermina/síntesis química , Evaluación de Medicamentos , Ratas , Distribución TisularRESUMEN
The C15O2 and 15O2 steady state techniques have been used to quantitatively measure regional blood flow (RBF) and regional oxygen utilisation (ROU) in a rabbit tumour model. RBF values of 4.6 +/- 0.6 ml min/100 cc were measured for normal muscle tissue and 11.0 +/- 3.0 ml/min/100 cc for tumour surface. Corresponding values for ROU were 18.3 +/- 3.5 mumol/min/100 cc for normal tissue and 39.7 +/- 20.1 mumol/min/100 cc for tumour surface. 18F-2-fluoro-2-deoxy-D-glucose (2FDG) was used in the same tumour model to measure glucose metabolic rate. The values obtained were 4.3 +/- 2.1 mumol/min/100 cc for normal muscle tissue and 53.8 +/- 18.3 mumol/min/100 cc for tumour tissue. Tumour growth was followed with a series of measurements of blood flow, oxygen, and glucose metabolism at intervals of 1 week. Tumour-to-muscle ratios increased more rapidly with time for 2FDG than for oxygen utilisation and blood flow. The effect of radiation on tumour and normal tissue was followed by measurements of RBF and ROU. RBF values increased both in tumour and normal muscle tissue during radiation and decreased during one week after radiation. ROU-values decreased (30%) in tumour and increased (45%) in normal muscle tissue during radiation. Even at one week after radiation, ROU-values were 30% lower in tumour and 45% higher in normal muscle tissue than before radiation.
Asunto(s)
Glucosa/metabolismo , Consumo de Oxígeno , Neoplasias de los Tejidos Blandos/irrigación sanguínea , Animales , Estudios de Seguimiento , Trasplante de Neoplasias , Consumo de Oxígeno/efectos de la radiación , Conejos , Flujo Sanguíneo Regional/efectos de la radiación , Neoplasias de los Tejidos Blandos/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
Positron tomography has been used to measure blood flow, oxygen utilization, and glucose metabolism in soft-tissue tumors in rabbits and in human tumors in extremities. Both blood flow and oxygen utilization were increased in tumor in contrast to normal muscle tissue. Oxygen extraction fraction was, however, decreased in tumor. The most sensitive indicator of tumor growth was the glucose metabolic rate. The effect of irradiation was observed by blood flow measurements in human tumors and by blood flow and oxygen utilization in tumors in rabbits. Blood flow increased both in tumor and normal muscle tissue during irradiation and decreased afterwards. Oxygen utilization decreased in tumor and increased in normal tissue during irradiation.