Library

Notes: Abstract The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [14C]clorgyline in normal, conscious rat brain. [14C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [14C]methyliodide. Sixty minutes after [14C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.

Notes: Abstract Metabolic studies of 18F-labeled 5-fluoro-2′-deoxyuridine (FdUrd), 5-fluorouridine(FUrd) and 5-fluorouracil (FUra) were performed in tumor-bearing rats and mice. Also, the usefulness of 18F-FdUrd and 3H-deoxythymidine (dThd) for tumor detection was compared. In the tumor, 2 h after the injection of the 18F-pyrimidines, 3%–11% and 6%–14% of the 18F was present in the nuclear and microsomal fractions, respectively, and 17%–34% and 19%–24% of the 18F was incorporated into the acid-insoluble and nucleotide fractions, respectively. Of the three 18F-pyrimidines, 18F-FUrd demonstrated the highest incorporation rate, while 18F-FUra showed the lowest incorporation rate. The incorporation in the spleen, small intestine, and liver was less than that in the tumor. 3H-dThd and 18F-FdUrd were injected into the same mice. The 3H-dThd was accumulated in the spleen, small intestine, and tumor, and in these three tissues significant amounts of the 3H were incorporated into acid-insoluble materials. However, the clearance of 18F-FdUrd was slow in the tumor but rapid in the spleen and small intestine. In the autoradiograms of the tumor, 18F and 3H showed a slightly different distribution. Both distribution patterns were unchanged when the soluble materials were rinsed out with perchloric acid. For tumor detection, 18F-FdUrd gives the same information as radio-dThd, and further information can be obtained by positron-emission tomography.

Notes: Abstract A method has been developed to quantitate regional cerebral blood blow (rCBF) using iodine-123-labelled N-isopropyl-p-iodoamphetamine (IMP). This technique requires only two single-photon emission tomography (SPET) scans and one blood sample. Based on a two-compartment model, radioactivity concentrations in the brain for each scan time (early: t e ; delayed: td) aredescribed as: % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaam4qamaaBa% aaleaacaWG0baabeaakmaabmaabaGaamiDamaaBaaaleaacaWGLbaa% beaaaOGaayjkaiaawMcaaiabg2da9iaadAgacqWIpM+zcaWGdbWaaS% baaSqaaiaadggaaeqaaOWaaeWaaeaacaWG0bWaaSbaaSqaaiaadwga% aeqaaaGccaGLOaGaayzkaaGaey4LIqSaamyzamaalaaabaGaamOzaa% qaaiaadAfadaWgaaWcbaGaamizaaqabaaaaOGaamiDamaaBaaaleaa% caWGLbaabeaaaaa!4D64!\[C_t \left( {t_e } \right) = fC_a \left( {t_e } \right) \otimes e\frac{f}{{V_d }}t_e \] and % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaam4qamaaBa% aaleaacaWG0baabeaakmaabmaabaGaamiDamaaBaaaleaacaWGKbaa% beaaaOGaayjkaiaawMcaaiabg2da9iaadAgacqWIpM+zcaWGdbWaaS% baaSqaaiaadggaaeqaaOWaaeWaaeaacaWG0bWaaSbaaSqaaiaadsga% aeqaaaGccaGLOaGaayzkaaGaey4LIqSaamyzamaalaaabaGaamOzaa% qaaiaadAfadaWgaaWcbaGaamizaaqabaaaaOGaamiDamaaBaaaleaa% caWGKbaabeaaaaa!4D61!\[C_t \left( {t_d } \right) = fC_a \left( {t_d } \right) \otimes e\frac{f}{{V_d }}t_d \] respectively, where ⊗ denotes the convolution integral; C a (t), the arterial input function; f rCBF; and V d , the regional distribution volume of IMP. Calculation of the ratio of the above two equations and a “table look-up” procedure yield a unique pair of rCBF and V d for each region of interest (ROI). A standard input function has been generated by combining the input functions from 12 independent studies prior to this work to avoid frequent arterial blood sampling, and one blood sample is taken at 10 min following IMP administration for calibration of the standard arterial input function. This calibration time was determined such that the integration of the first 40 min of the calibrated, combined input function agreed best with those from 12 individual input functions (the difference was 5.3% on average). This method was applied to eight subjects (two normals and six patients with cerebral infarction), and yielded rCBF values which agreed well with those obtained by a positron emission tomography H2 15O autoradiography method. This method was also found to provide rCBF values that were consistent with those obtained by the non-linear least squares fitting technique and those obtained by conventional microsphere model analysis. The optimum SPET scan times were found to be 40 and 180 min for the early and delayed scans, respectively. These scan times allow the use of a conventional rotating gamma camera for clinical purposes. V d values ranged between 10 and 40 ml/g depending on the pathological condition, thereby suggesting the importance of measuring V d for each ROI. In conclusion, optimization of the blood sampling time and the scanning time enabled quantitative measurement of rCBF with two SPET scans and one blood sample.

Notes: Abstract To elucidate the mechanism of large neutral amino acid (LNAA) transport in cerebral gliomas and to evaluate the clinical usefulness of positron emission tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18 patients with cerebral glioma using dynamic PET and18F-Phe. By employing two-compartment model analysis, the influx rateK 1, the efflux ratek 2 and the distribution volume (V d) of18F-Phe were estimated in tumour tissue and contralateral normal grey matter.18F-Phe showed increased accumulation in tumour tissue regardless of the grade of malignancy in all patients. The rate of uptake of18F-Phe in high-grade glioma was significantly higher than in low-grade glioma (P 〈0.05). However, it was difficult to evaluate the tumour grade only from the18F-Phe accumulation in individual cases. Values ofK 1 andV d were significantly increased in the tumour tissue. TheK 1 value of the tumour tissue tended to decrease with increasing LNAA concentration in plasma. Therefore, influx of18F-Phe into tumour tissue is mainly related to the carrier-mediated active transport. It is concluded that PET with18F-Phe is of clinical value for tumour detection rather than assessment of tumour malignancy.

Notes: Abstract The effect of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain was investigated in vivo. After administration of HA1077, at doses of 0.1, 0.3, and 3 mg/kg, 5-hydroxyindoleacetic acid (5-HIAA) levels increased in most regions except midbrain. In the striatum, parallel increases of both serotonin (5-HT) and 5-HIAA levels were observed at 0.3 mg/kg, but only the 5-HT level increased at 0.1 mg/kg. These results suggest that HA1077 may activate the turnover or synthesis of 5-HT. After administration of HA1077 at 0.3, 1, and 3 mg/kg, the dopamine (DA) level was increased in the striatum, but 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid levels were unchanged. After HA1077 administration at 1 mg/kg, both DA and DOPAC levels increased in the hypothalamus and only DA level increased in the cerebral cortex. By contrast, DOPAC level decreased in the midbrain after HA1077 treatment at 0.1 and 0.3 mg/kg, and in the brainstem at 0.1 and 10 mg/kg. The ratio of [3H]-N-methylspiperone accumulation relative to that in the cerebellum did not change after HA1077 treatment at any of the doses employed. Thus, the effects of HA1077 on neurotransmitter metabolism are complex and vary depending on the dosage and sites of the brain. Although the dose-dependent effects of HA1077 on neurotransmitter metabolism are similar to those of calcium entry blockers, HA1077 can facilitate DA synthesis in the hypothalamus and striatum, unlike the calcium entry blockers.

Notes: Abstract 18F-labeled 5-fluorouracil(FUra), 5-fluoro-2′-deoxyuridine(FdUrd), and 5-fluorouridine(FUrd) were synthesized with high radiochemical purities. The 18F-labeled pyrimidines were injected into rats. The metabolites in serum, bile, and urine were analyzed up to 2 h after administration by radio-high performance liquid chromatography(HPLC). The blood clearance of three pyrimidines was very rapid. In the serum the nucleosides and base disappeared very rapidly with a biological half-life of about 2 min and most of them had disappeared by 60 min. The metabolites in the urine were similar to those in the serum. In the bile pyrimidine nucleosides and base were not detected. 18F was found in the metabolites. Our results explain the high uptakes in the kidney and liver in biodistribution studies of the 18F-labeled pyrimidines.