Autoradiographic method for quantitative evaluation of the blood-brain barrier effects of contrast media

Opening of the blood-brain barrier after intravenous injection of different contrast media has been investigated by a quantitative autoradiographic technique using 14C-aminoisobutyric acid (AIB) as the blood-brain barrier radiotracer. In this study, experiments were carried out in adult rats. Animals were injected intravenously with 2 ml/kg of the tested contrast medium, and immediately afterward with the blood-brain radiotracer AIB. The following contrast media have been tested: diatrizoate 38%, ioxithalamate 38%, ioxaglate 38%, the nonionic product metrizamide 40%, and a new nonionic product P-297, 400 mg l/ml. Control animals were injected intravenously with saline 0.9% (2 ml/kg) before the injection of the tracer. The degree of blood-brain barrier opening was quantitatively assessed by calculating the capillary rate constant for blood-to-brain transfer of AIB (ki) from the brain activity and the arterial integral for a 6 min experiment. Preliminary data seem to indicate that the intravenous injection of 2 ml/kg of a constant medium may produce a tiny opening of the blood-brain barrier. But, if this is so, this blood-brain barrier opening is of a very low magnitude in the normal brain and there are no obvious differences between the test contrast agents injected intravenously.     

Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [¹⁴C]2-deoxyglucose ([¹⁴C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [¹⁴C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [¹⁴C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [¹⁴C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.     

内皮型一氧化氮合酶在急性放射性脑水肿中的表达

目的：探讨大剂量＾６０Ｃｏγ刀照射后脑血管内皮细胞内皮型一氧化氮合酶（ｅＮＯＳ）表达变化及其与急性放射性脑水肿的关系。方法单次２００Ｇｙ＾６０Ｃｏγ刀照射大鼠右侧尾状核头部,于照射后１４ｄ内分批活杀动物,采用光镜,电镜、免疫组化及原位杂交技术研究照射后急性放射性脑水肿的发生发展及脑血管内皮细胞ｅＮＯＳ表达变化。结果照射后２ｈ出现急性放射性脑水肿病理改变。照射后３ｄ达高峰;脑血管内皮细胞ｅＮＯＳ于照     

Effect of intracarotid injection of iopamidol on local cerebral glucose utilization in rat brain

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of intracarotid injection of a nonionic, low-osmolar contrast medium (iopamidol) on local cerebral glucose utilization in the rat brain. Contrast medium was injected at 20 degrees C and at 37 degrees C, and the relative changes in local cerebral glucose utilization were measured. At 20 degrees C the viscosity of the contrast agent was about twice that of the same solution at 37 degrees C, and resulted in a statistically significant increase in local cerebral glucose utilization in the hemisphere ipsilateral to the side of intracarotid infusion. Saline control studies showed that the metabolic change was not related to either the solution temperature or the osmolality. These findings suggest that increased viscosity of a contrast medium may contribute to its neurotoxic effects during cerebral angiography, hence emphasizing the importance of preheating contrast material to avoid adverse reactions.     

电针对急性脑梗死的作用机制研究——对家兔脑动态CT时间-密度曲线的影响

目的:通过家兔颅脑动态CT时间-密度曲线分析,了解针刺后急性脑梗死家兔血脑屏障的改变,进一步探讨针灸治疗急性期脑梗死的机制。方法:采用家兔自体血栓栓塞,建立急性脑梗死家兔模型,电针刺激督脉经穴“百会”、“水沟”治疗,观察电针对急性脑梗死家兔脑组织血管内血流灌注和血管内血流充盈时间的影响。结果:电针能明显增加缺血区脑组织的血灌流量,降低缺血区血管内血流充盈时间。电针刺激后各组指标与模型组比较有显著性差异(P<0.01)。结论:电针对急性脑梗死家兔血脑屏障具有明显的保护和修复作用,其作用机制可能与针刺能有效改善脑部血灌流量、改变了脑组织缺血缺氧的状况、减少脑梗死发作后引起的脑水肿、从而减少对血脑屏障的破坏作用有关。     

Acute blood-brain barrier opening in experimentally induced focal cerebral ischemia is preferentially identified by quantitative magnetization transfer imaging.

Pathologic changes in brain tissue during and after stroke may lead to injury of the blood-brain barrier (BBB) and subsequent hemorrhagic transformation (HT). In a rat model of HT, the apparent diffusion coefficient of water, cerebral blood flow, relaxation times, T(1) and T(2), and magnetization transfer (MT) related parameters (T(1sat), K(for) and the MT ratio) were repetitively measured during 3 h of focal ischemia and 2 h of reperfusion (n = 8). Areas of BBB opening were identified by sequential assay of the transcapillary influx of Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) by MRI and (14)C-alpha-aminoisobutyric acid (AIB) by quantitative autoradiography. Ischemia-injured regions of interest were identified from the MRI data and divided into those with and without BBB opening. Of the several MRI parameters measured, the T(1sat) in the caudate-putamen and preoptic area during ischemia and the first 2 h of reperfusion correlated best with the regional pattern of BBB opening observed thereafter. These data suggest that an ipsilateral/contralateral T(1sat) ratio > 1.6 demarcates leakage of small molecules such as Gd-DTPA and AIB across the BBB. As to clinical relevance, the quantitation of MT parameters in acute stroke may enable the early detection of areas of BBB opening and potential HT.     

Effect of moderate level x-radiation to brain on cerebral glucose utilization

The effect of x-radiation in doses used in treatment of brain malignancies has previously been established largely by histologic examination of the tissue or by observation of a deficit in function. At moderate dose levels such effects are usually delayed and are vascular in origin. We have used the 2-[14C]deoxyglucose method for the quantitative measurement of local cerebral glucose utilization to learn whether x-radiation administered to rat brain in a dose below that which is known to result in any histologic change may nevertheless affect the brain's local rates of glucose utilization. Measurements were made 4 days and 4 weeks after exposure of groups of rats to 1,500 rad. Rates of glucose utilization in 54 gray and eight white matter structures in both groups were compared with rates in sham-irradiated controls. Statistically significantly lower rates were found in 16 structures in rats 4 days after radiation and in 25 structures 4 weeks after radiation exposure. A weighted average rate for the brain as a whole was approximately 15% below that of the controls for both radiated groups, but this difference was short of being of statistical significance. It is clear from this study that the metabolic rates of some brain structures are reduced following moderate doses of x-radiation.     

Differentiation of cerebral radiation necrosis from tumor recurrence by [18F]FDG and 82Rb positron emission tomography

Nine radiation-treated brain tumor patients were studied by positron emission tomography (PET) in an attempt to differentiate tumor recurrence from radiation necrosis. Rubidium-82 was used to define the region of absent or disturbed blood-brain barrier and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) was used to evaluate the metabolic state of the brain. By comparing glucose utilization in the pathologic region with utilization in the adjacent tissue, a diagnosis of recurrent tumor (increased [18F]FDG accumulation) or necrosis (decreased FDG accumulation) was made. In the seven patients who underwent surgery the PET diagnosis was confirmed by histologic examination of resected tissue. The two patients who did not undergo surgery have had a clinical course consistent with the PET diagnosis of necrosis. Dynamic 82Rb imaging showed that the rate of 82Rb accumulation was greater in tumor than in normal brain. However, this finding alone did not differentiate tumor from necrosis, as some necrotic tissue also showed high rates of 82Rb accumulation, and washout kinetics were similarly nonspecific. The differentiation of radiation necrosis from tumor recurrence is reliably achieved by [18F]FDG PET examination and is aided by information obtained from a 82Rb PET study done immediately prior to the [18F]FDG injection.     

镧示踪法观察常规分割外照射后血脑屏障的超微结构改变

目的 观察Sprague-Dawley(SD)大鼠全脑常规外照射后血脑屏障(BBB)的超微结构变化特点及其规律。方法 SD大鼠20只,分为5个实验组,60Coγ射线全脑常规分割外照射,各组受照后16h以硝酸镧为示踪剂,用透射电镜观察BBB超微结构变化。结果 对照组镧颗粒分布在血管腔内,BBB结构完整;10Gy组少量镧颗粒通过开放的毛细血管内皮细胞间的紧密连接,沉积于基底膜,但未入脑组织;20Gy组见大部分紧密连接开放,镧颗粒弥漫性分布于神经细胞间隙,细胞内无镧颗粒沉积;30Gy神经细胞质内见大量、核内见少量镧颗粒沉积;40Gy组部分毛细血管内皮细胞及神经细胞失去正常形态,结构破坏,大量镧颗粒沉积在细胞核内、外。结论 放射线具有降低及破坏BBB功能的作用,且与照射剂量呈正相关;30Gy后BBB完全开放,此时进行化疗为最佳时机;照射40Gy后不易再全脑追加剂量,否则会导致不可逆性放射性脑损伤。     

Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia.

The ability of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced MRI to localize and quantitate blood-brain barrier (BBB) opening was evaluated against quantitative autoradiographic (QAR) imaging of (14)C-alpha-aminoisobutyric acid (AIB) distribution. The blood-to-brain transfer constant (K(i)) for Gd-DTPA was determined by MRI in rats after 3 h of focal cerebral ischemia plus 2.5 h of reperfusion (n = 9), and that of AIB was determined by QAR shortly thereafter. Tissue regions of interest (ROIs) for Gd-DTPA leakage were identified by ISODATA segmentation of pre- and post-Gd-DTPA Look-Locker (L-L) T(1) maps. Patlak plots were constructed using time course of blood and tissue T(1) changes induced by Gd for estimating K(i). Among the nine rats, 14 sizable regions of AIB uptake were found; 13 were also identified by ISODATA segmentation. Although the 13 MRI-ROIs spatially approximated those of AIB uptake, the segmentation sometimes missed small areas of lesser AIB uptake that did not extend through more than 60% of the 2.0-mm-thick slice. Mean K(i)'s of AIB were highly correlated with those of Gd-DTPA across the 13 regions; the group means (+/-SD) were similar for the two tracers (7.1 +/- 3.3 x 10(-3) and 6.8 +/- 3.5 x 10(-3) ml.g(-1) . min(-1), respectively). In most instances, Gd-DTPA MRI accurately localized areas of BBB opening.     

银杏叶提取物对模拟高原低氧暴露下大鼠血脑屏障的保护作用

目的观察银杏叶提取物(GBE)对模拟高原低氧暴露下大鼠血脑屏障的保护作用,并初步阐明其机制。方法将48只SD大鼠随机分为4组,低压舱模拟海拔高度7000m连续减压缺氧3d制备大鼠实验性高原脑水肿模型。GBE前期干预组在缺氧前3d按60mg/(kg.d)给予GBE干预处理,GBE后期干预组在缺氧开始24h后按相同剂量给予GBE至减压缺氧结束,以湿干比值法评价其对脑含水量的影响,硝酸镧示踪法观察GBE对低氧暴露下血脑屏障通透性的影响。结果 GBE前期干预组和GBE后期干预组大鼠脑含水量和硝酸镧颗粒渗出均明显少于高原对照组(P<0.01),且GBE前期干预组的效果显著优于GBE后期干预组(P<0.01)。结论 GBE对低氧暴露下血脑屏障通透性增高具有一定保护作用。     

VEGF mRNA及蛋白在大鼠放射性脑损伤模型中的动态变化

目的 研究VEGF mRNA及蛋白在大鼠放射性脑损伤模型中的动态改变。方法 健康SD大鼠114只,按随机数字表法分为假照组（麻醉后不照射,42只）和照射组[20 Gy电子线（6 MeV）单次全脑照射SD大鼠建立放射性脑损伤模型,72只],分别于照射后1、3、7、14、28、42、56 d被处死,取全部脑组织。通过HE染色光镜观察病理学变化,实时荧光定量反转录多聚酶链反应检测VEGF mRNA表达变化,Western blot检测全脑VEGF总蛋白含量改变,免疫组织化学结合计算机图像处理检测脑血管内皮细胞、胶质及神经细胞VEGF蛋白积分光密度值变化。结果 照射组脑组织在观察期主要历经了脑血管内膜细胞受损、血管源性水肿、血栓发生、血栓消融、血管再通及新生等病理变化过程。照射组VEGF mRNA在照后1~56 d出现下降,其中1、3、7、28和42 d降低与假照射组比较,差异有统计学意义（t=16.275~46.118,P<0.05）。VEGF总蛋白在照后1和7 d表达增高,3、14、28、42、56 d表达相对降低。照后1 d起脑组织即出现VEGF染色阳性的血管内皮细胞、胶质及神经细胞。照后1、14、42、56 d胶质及神经细胞VEGF蛋白光密度值出现显著升高,与假照射组比较,差异有统计学意义（t=-8.394~-4.697,P<0.05）,血管内皮细胞在照后1、14、42 d VEGF蛋白光密度值升高（t=-5.554~-4.159,P<0.05）。结论 在放射性脑损伤模型中,大鼠脑组织中VEGF mRNA表达受到相对抑制;VEGF总蛋白仅在损伤急性期升高;脑血管内皮细胞、胶质及神经细胞表达的VEGF蛋白在观察期内持续上调,并参与了急性期内诱导水肿、形成血栓以及在早发延迟期内血管修复与再生、血栓消融等相关事件。     

Index of lipid peroxidation and glucose utilization in the cerebrospinal fluid in patients with cerebral infarction

Cerebral ischemia could be observed as acute metabolic crisis, when oxygen and glucose supply is compromised and synthesis of energy is insufficient. Apart from the excitotoxicity, increased production of reactive oxygen species with consequent lipid peroxidation is also included in neuronal cell damage. Furthermore, these toxic compounds could also be produced during the process of secondary inflammation of ischemic tissue. In the early stage of ischemia, as a systemic response to acute stress, there is an increase in glucose level in cerebrospinal fluid (CSF) and peripheral blood. According to the metabolic crisis and acidosis in ischemic brain tissue we investigated index of lipid peroxidation (ILP) and glucose utilization (IGU) in CSF of 53 patients of both sexes, aged 55-70 years with cerebral infarction. Control group comprised 15 patients with sudden onset of motor deficit subjected to diagnostic lumbar radiculography and suspected on discal genesis. ILP in CSF, as the indicator and sequela of neuronal cell membranes damage, was two fold increased in the acute period of cerebral infarction and maximal values (3.5 times) were noticed 24 hours after the ischemic episode compared to controls. Besides the increase in glucose concentration in peripheral blood and CSF of patients with cerebral infarction, IGU was decreased (37%) with minimal values (32%) 24 hours after the ischemia. These changes indicate that glucose is available but cells are incapable to metabolize it. We concluded that ILP and IGU in CSF of patients with cerebral infarction could be indicators of metabolic dysfunction and neuronal cell damage. Also, these results suggest the significance of polyvalent therapy including antioxidative and antiinflammatory agents in acute phase of cerebral ischemia.     

全脑常规照射开放血脑屏障动物模型的建立

目的 建立全脑常规照射开放血脑屏障（blood—brain barrier，BBB）的鼠动物模型。方法 100只SD大鼠随机分为5组，依次为假照射组、10、20、30和40Gy组，每组20只，^60Coγ射线全脑常规照射，2Gy，次，5次，周，每日观察大鼠饮食、自主活动、并记录照射区皮肤与毛发、体重及神经系统症状变化，照射后16h每组随机选取4例用镧示踪电镜化学技术观察大鼠BBB超微结构的变化。结果实验大鼠均未出现可评价的异常神经行为及体征；各组的饮食、自主活动、皮肤与毛发无可评价的异常改变；体重增加无统计学意义（P〉0．05）。透射电镜观察显示照射后随照射剂量的增加出现BBB功能的改变，且与照射剂量呈正相关。结论该模型能较好地模拟临床放射治疗过程，易于操作，成功率高，是全脑常规照射后从病理生理学及分子生物学等方面研究BBB功能变化规律的良好模型。     

Tracer feasibility for monitoring tumor radiotherapy: a quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67.

In a rat AH109A tumor model, metabolic tracers for glucose, amino acid, and nucleic acid metabolisms (2-deoxy-2-[18F]fluoro-D-glucose (18FDG), L-[methyl-14C]methionine (14C-Met), [6-3H]thymidine (3H-Thd), and 2'-deoxy-5-[18F]fluorouridine (18FdUrd], and the conventional radionuclide 67Ga-citrate were used to assess the feasibility of monitoring tumor radiotherapy using a quadruple tracer technique. Two combinations of four tracers (18FDG or 18FdUrd, 14C-Met, 3H-Thd and 67Ga) were compared in a time-course study after single-dose irradiation (20 Gy) and were also used in a dose-dependency study performed 6 days after 5, 10, 15, or 20 Gy of irradiation. Fluorine-18-FDG showed a large change in uptake and a steady response to radiotherapy. Fluorodeoxyuridine showed a rapid decrease after radiotherapy, but the range of change in uptake was narrow. Gallium-67 could not detect tumor response early after treatment, but showed a marked change in uptake later. [6-3H]Thd and 14C-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that they may be feasible for PET studies.     

Evaluation of [1-11C]-alpha-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies

Alpha-aminoisobutyric acid (AIB), or alpha-methyl alanine, is a nonmetabolized amino acid transported into cells, particularly malignant cells, predominantly by the 'A' amino acid transport system. Since it is not metabolized, [1-11C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g. positron tomography). The tissue distribution of [1-11C]-AIB was determined in six dogs bearing spontaneous tumors, including lymphosarcoma, osteogenic sarcoma, mammary carcinoma, and adenocarcinoma. Quantitative imaging with tissue radioassay confirmation at necropsy showed poor to excellent tumor localization. However, in all cases the concentrations achieved appear adequate for amino acid transport measurement at known tumor locations. The observed low normal brain (due to blood-brain barrier exclusion) and high (relative to brain) tumor concentrations of [1-11C]-AIB suggest that this agent may prove effective for the early detection of human brain tumors.     

Radiation-induced brain metabolic changes in the acute and early delayed phase detected with quantitative proton magnetic resonance spectroscopy

OBJECTIVE: Quantitative proton magnetic resonance spectroscopy (MRS) was performed before and after radiation therapy to estimate its usefulness for evaluating radiation-induced metabolic brain changes. METHODS: Twenty patients with multiple brain metastases not having received any previous brain radiation were selected for the study. The total radiation dose varied from 40 (20 fractions) to 50 (25 fractions) Gy, with an opposition technique. MRS was performed just before irradiation, during the acute phase (n = 20, 8.5 +/- 4.6 days) and in the early delayed phase (n = 15, 3.6 +/- 0.5 months) after radiation. The concentration of N-acetyl-L-aspartate (NAA), choline-containing substance (Cho), and creatine/phosphocreatine (Cr) was quantified. RESULTS: The concentration of NAA decreased (P = 0.05 versus before radiation), and the concentration of Cho increased (P = 0.006 versus before radiation) during the early delayed phase. The concentration of Cr was not changed before or after radiation. CONCLUSIONS: Radiation-induced changes in brain metabolism were well detected with quantitative MRS in the early delayed phase. Quantitative MRS is a novel tool for estimating radiation-induced neurotoxicity.     

Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 1: Pharmacology of technetium-99m ECD in nonhuman primates

Technetium-99m ethyl cysteinate dimer ([99mTc]ECD) is a neutral, lipophilic complex which rapidly crosses the blood-brain barrier. Brain retention and tissue metabolism of [99mTc]ECD is dependent upon the stereochemical configuration of the complex. While both L,L and D,D enantiomers are extracted by the brain, only the L,L but not the D,D form, is metabolized and retained in the monkey brain (4.7% injected dose initially, T 1/2 greater than 24 hr). Dynamic single photon emission computed tomography imaging studies in one monkey indicates 99mTc-L,L-ECD to be distributed in a pattern consistent with regional cerebral blood flow for up to 16 hr postinjection. Dual-labeled 99mTc-L,L-ECD and [14C]iodoantipyrine autoradiography studies performed 1 hr after administration show cortical gray to white matter ratios of both isotopes to be equivalent (approximately 4-5:1). These data suggest that 99mTc-L,L-ECD will be useful for the scintigraphic assessment of cerebral perfusion in humans.     

Reproducibility of cerebral glucose utilization measured by PET and the [18F]-2-fluoro-2-deoxy-d-glucose method in resting, healthy human subjects

The stability of cerebral glucose utilization was examined in nine right-handed, healthy men (age, 24.88 +/- 2.93 years) using positron emission tomography (PET) and the [18F]-fluorodeoxglucose (FDG) method. Each study was run twice at intervals of 1-12 weeks with the subject at rest. The average cerebral metabolic rate for glucose (CMRGlu) was 5.40 +/- 0.71 mg/100 g per min (coefficient of variance, 13.08). The average intraindividual variation of CMRGlu was 7.91% +/- 15.46% (P = 0.13). Metabolic indices (MI: regional/mean cortical CMRGlu) were used to determine the regional cerebral metabolic distribution. The interindividual (coefficient of variance, 7.13) and intraindividual variabilities (average variation, -0.12% +/- 8.76%) of MI were smaller than those of metabolic rates. No reproducible significant asymmetry was observed. The FDG method used with subjects at rest thus yields low intraindividual variability of both cerebral glucose consumption and regional metabolic distribution, even at an interval of several weeks. Cerebral glucose utilization measured under such conditions may act as a reliable reference for determination of the influences of physiological (activation), pharmacological or pathological processes on cerebral glucose metabolism.     

Is [1-11C]putrescine useful as a brain tumor marker?

Our experience with 11C-putrescine underscores the difficulty of finding a selective brain tumor tracer, uniquely incorporated by neoplastic glia or metastatic cells within brain, but not by the proliferating, nontransformed cells which constitute a normal pathophysiological reaction to various disease processes. Thirty-three patients with 36 lesions were studied with 11C-putrescine to determine the specificity of labeled putrescine for tumor tissue. The uptake of 11C-putrescine was correlated with local cerebral glucose metabolic rate in various lesions, including different types of tumors, to assess the relationship between 11C-putrescine uptake and tumor biology. Carbon-11-putrescine uptake was similar in malignant tumor and benign, non-neoplastic lesions with blood-brain barrier breakdown, illustrating the lack of tumor specificity of this tracer. Carbon-11-putrescine was not well incorporated into poorly enhancing lesions, regardless of their pathology, emphasizing the requirement of a disrupted blood-brain barrier for 11C-putrescine uptake. The ratio of 11C concentration within lesions, compared to that in a region of interest in the contralateral brain, weakly correlated with an analogous ratio for local cerebral glucose metabolic rate in various lesions. Physiological processes not unique to tumors are associated with polyamine active transport and metabolism and contribute to the lack of tumor specificity of 11C-putrescine. Carbon-11-putrescine appear to have less diagnostic utility than 18FDG in brain tumors. The potential of 11C-putrescine for evaluating the effect of antineoplastic therapy and providing prognostic information on brain tumors remains to be investigated.