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We carried out a study to evaluate treatment response and residual mass in lung cancer with positron emission tomography (PET), using l-[methyl-C]methionine (MET). MET tumour uptake and tumour volume measured by computed tomography (CT) before and within 2 weeks after radiotherapy or chemoradiotherapy were compared in 43 studies of 21 patients. Ten patients with local control (no recurrence) of tumour showed a larger decrease in MET uptake (65.2%±12.2%) than in tumour volume (50.8%±9.6%, P<0.01). Five patients with early recurrence (from 1 to 4 months) showed smaller decreases in both MET uptake (22.2%±13.5%) and tumour volume (28.6%±20.0%) than those in the no-recurrence group ( P<0.01). Four patients with late recurrence (after 11 months or more) showed a similar decrease to the no-recurrence group in MET uptake (72.8%±14.8%) but little change in tumour volume (18.5%±19.0%), the latter result corresponding to that in the early-recurrence group. Using tumour volume only, the no-recurrence group was differentiated from both the early- and the late-recurrence group ( P < 0.01), but the early-recurrence group was not differentiated from the late-recurrence group. Using the MET uptake data, the early-recurrence group was clearly distinguished from the late-recurrence group ( P<0.01), but the late-recurrence group was indistinguishable from the no-recurrence group. CT was useful in distinguishing the no-recurrence group from the groups in which there was ultimate recurrence, whether early or late. When a residual mass is seen on CT, PET seems to be helpful in evaluating tumour viability. [ABSTRACT FROM AUTHOR]

The metabolites of L-[methyl-C]methionine in the plasma of 8 patients with tumor were measured for 60 min after injection. In the plasma, after a rapid clearance, the total radioactivity remained constant, and protein-bound radioactivity increased rapidly. Non protein metabolites detected by HPLC as at least two components besides methionine, increased with time. Significant individual variations for the metabolism were observed. AT 60 min after injection, 36.5% (range: 16%-72%) and 45.3% (range: 13%-74%) of the C was measured as methionine and labeled proteins, respectively. [ABSTRACT FROM AUTHOR]

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors. [ABSTRACT FROM AUTHOR]

In vivo binding of 3- N-[C]methylspiperone ([C]NMSP) was saturable in the rat forebrain, but not in the cerebellum. Nonspecific binding was almost equivalent in all brain regions except for the white matter. [C]NMSP binding was localized to receptor-rich fractions when low doses were administered (less than 20 nmol/kg body weight). The striatum-to-cerebellum ratio was a function of time after injection and administered dose. This radio remained constant in low doses of under 30 nmol/kg. The radioactivity curve of the cerebellum in a control positron-emission tomographic study almost equaled that of the striatum in the dog pretreated with spiperone (2 mg). This indicates that the amount of binding in the cerebellum might be considered a nonspecific binding and unbound pool. The data obtained by the pretreatment study was different from that of displacement, which suggested that displaceable [C]NMSP in the specific binding sites of the striatum was not completely cleared from the brain tissue by a large amount of unlabeled spiperone. [ABSTRACT FROM AUTHOR]

We prepared 2-deoxy-2-[F]fluoro- d-galactose as a potential radiopharmaceutical for liver imaging and for the assessement by position emission tomography of regional metabolic function of the liver. In biodistribution studies of rats, the liver uptake of the compound was very high, almost reaching a plateau (6.33% dose/g) at 30 min and remaining constant until 120 min. This high uptake was reduced by simultaneous administration of d-galactose, but d-glucose had no effect. The compound was much less concentrated in the liver that had been damaged by CCl treatment. Positron imaging of a rabbit liver showed a remarkable uptake of the compound with a high liver-to-blood ratio. The high concentration in the liver was also reduced by the administration of d-galactose. These data suggest that the compound was trapped in the liver by a metabolic process and could be used for the measurement by position emission tomography of galactose metabolism in the liver. [ABSTRACT FROM AUTHOR]

C-S-Adenosyl- l-methionine (C-SAM) was synthesized enzymatically from C- l-methionine using ratliver extract [40%-50% saturated (NH)SO fraction] as the enzyme source. In biodistribution studies in rats, the highest uptake of C-SAM was found in the kidneys. C-SAM was also accumulated in the small intestine, pancreas, adrenal gland, liver, and spleen. The uptake of C-SAM in the brain increased with time, but remained low. At 30 min after injection, about 50%-60% of the C radioactivity was present in the acid-insoluble fraction of the kidneys and liver. When a high loading dose of C-SAM was administered, the kidney uptake was enhanced, but the proportion of the radioactivity present in the acid-insoluble fraction was lower. In a study of one rabbit, the kidney uptake was of -SAM clearly visualized using positronemission tomography. [ABSTRACT FROM AUTHOR]

The myocardial uptake of F-FDG was investigated under various conditions, and compared with brain and tumor uptake as a function of blood glucose level. The uptake by the heart of normal feeding rats was rapid and remained essentially unchanged up to 2 h after F-FDG injection, approximately 3%-4% dose/g tissue. On the other hand, the myocardial uptake of fasted rats was significantly lower than that of control rats throughout the course of the study, and it was about 0.3%-0.4% dose/g tissue. Myocardial uptake of F-FDG was relatively constant at glucose levels under about 120 mg/100 ml and increased steeply at higher blood glucose levels. In contrast, brain uptake decreased linearly with increasing levels of blood glucose, revealing a strong negative correlation between brain uptake of F-FDG and blood glucose levels. The tumor uptake pattern remained relatively unchanged, irrespective of blood glucose levels. It was revealed that the glucose demands of brain, heart, and tumor were entirely different. After a glucose load, the myocardial uptake of fasted rats increased only slightly from 0.4% to 0.6% dose/g tissue, in spite of transitional hyperglycemia. In contrast, insulin caused myocardial uptake to increase extraordinarily, although it caused a decrease in blood glucose levels. [ABSTRACT FROM AUTHOR]

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

F-labeled 5-fluorouracil(FUra), 5-fluoro-2′-deoxyuridine(FdUrd), and 5-fluorouridine(FUrd) were synthesized with high radiochemical purities. The F-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. F was found in the metabolites. Our results explain the high uptakes in the kidney and liver in biodistribution studies of the F-labeled pyrimidines. [ABSTRACT FROM AUTHOR]

Three F-labeled pyrimidines, F-5-fluorouridine (F-5-FUR), F-5-fluorouracil (F-5-FU), and F-5-fluorodeoxyuridine (F-5-FdUR), were examined regarding tissue distribution and tumor uptake in ascitic hepatoma AH109A-bearing rats. The differential absorption ratios of tumors of F-5-FUR, F-5-FU, and F-5-FdUR were 0.75±0.21, 0.92±0.15, and 0.96±0.24 at 30 min, and 0.37±0.09, 0.64±0.34, and 0.60±0.17 at 120 min, respectively. The tumor-to-organ ratios obtained with three radiopharmaceuticals, especially with blood, heart, lung, muscle, and brain were high and these ratios increased with time. The tumor-to-organ ratios obtained with F-5-FdUR were always 1.3-4 times higher than F-5-FU and F-5-FUR. We concluded that F-5-FdUR was a suitable radiopharmaceutical for tumor imaging. Positron emission tomography of a rabbit tumor located on the chest with F-5-FdUR clearly showed the tumor within 1 h. [ABSTRACT FROM AUTHOR]