Taiju Matsuzawa

Assessment of radiotherapeutic effects on experimental tumors using 18F-2-fluoro-2-deoxy-D-glucose

The purpose of this study is to evaluation the effect of tumor volume and radiotherapy on the uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). The tumor models used were mouse mammary carcinoma MM48, FM3A, and rat hepatoma AH109A. Results were expressed as an 18FDG uptake ratio. This was the ratio of irradiated tumor uptake of 18FDG to unirradiated tumor uptake. The total tumor uptake was expressed as 18FDG uptake ratio multiplied by relative tumor volume. Following 20 Gy irradiation of the radioresistant tumor (MM48), the 18FDG uptake ratio was found to be unchanged, whereas in radiosensitive tumors (FM3A) the 18FDG uptake ratio was 0.37, the relative tumor volume was 0.31, and the calculated total tumor uptake was 0.11 on the eighth day after irradiation. The total tumor uptake was lower than the relative tumor volume. AH109A began to regrow after ten Gy irradiation, accompanied by elevated uptake of 18FDG on the seventh day. These results suggest that the 18FDG uptake by tumor is a good marker of radiotherapeutic effects as well as relapses of cancers and is more sensitive than morphological methods.

Effects of smoking on regional cerebral blood flow in neurologically normal subjects.

The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects, were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. One hundred and eleven subjects, who had no abnormalities in neurological examinations nor in CT scans, were divided into two groups: smokers (37) and non-smokers (74). Those who had a smoking index (Number of cigarettes/day) × (years of smoking history) greater than 200 were designated as smokers. The mean smoking index of smokers was 760. Sixty-two of the 74 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 17. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF, 12.5% lower in smokers, p less than 0.001). Increased reduction of CBF with advancing age was also observed. Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduces CBF. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels.

Experimental study for cancer diagnosis with positron-labeled fluorinated glucose analogs: [18F]-2-fluoro-2-deoxy-D-mannose: A new tracer for cancer detection

Abstract18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 18F-2-fluoro-2-deoxy-D-mannose (18F-FDM) were tested as tumor diagnostic agents in a transplantable rat tumor and rabbit tumors. Tissue distribution studies in rats showed high tumor uptakes of both radiopharmaceuticals. The tumor uptake reached 2.65±0.61% dose 18F-FDG/g and 2.65±0.81% dose 18F-FDM/g at 60 min and remained relatively constant until 120 min. Blood clearance of both 18F-FDG and 28F-FDM was very rapid and tumor-to-blood ratios reached 22.1 and 29.4 at 60 min, respectively. Tumor-to-tissue ratios of both radiopharmaceuticals were very high in most organs, especially in the liver, kidney, and pancreas.Positron emission tomography (PET) of rabbit tumor with 18F-FDM clearly delineated the main tumor, central necrosis, and lymph node metastases. These data suggested that 18F-FDM which is a by-product of 18F-FDG synthesis, was also an excellent cancer diagnostic agent as well as 18F-FDG. This is not only a new feature of 18F-FDM, but also an economical improvement on cancer diagnosis by PET.

Clinical assessment of therapeutic effects on cancer using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography: preliminary study of lung cancer.

Using positron emission tomography, we studied the tumor uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG) in five lung cancer patients before and after anti-cancer therapy (radiotherapy and/or chemotherapy). The tumor uptake of 18FDG was classified as positive and negative; the former, by increasing the uptake of 18FDG with time, and the latter, by decreasing or the constant uptake of 18FDG. Before therapy, all cases tested positive. After therapy, three cases were negative and two cases remained positive. All negative cases corresponded to complete second 18FDG study. Our findings in the 18FDG study correlate with the clinical results. 18FDG is a promising method for assessing therapeutic effects on cancer clinically.

Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography

We have studied the characteristics of carbon‐11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11QPyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45–60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon‐11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 ± 0.071. Intravenous administration of d‐chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 ±0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal.

Tumour Regrowth after Irradiation

SummaryStructural changes in irradiated tumours and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm3 of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumours were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 3000 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed.Structural changes in irradiated tumors and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm3 of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumors were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 3000 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed.

Studies on 18F-labeled pyrimidines. Tumor uptakes of 18F-5-fluorouracil, 18F-5-fluorouridine, and 18F-5-fluorodeoxyuridine in animals

Three 18F-labeled pyrimidines, 18F-5-fluorouridine (18F-5-FUR), 18F-5-fluorouracil (18F-5-FU), and 18F-5-fluorodeoxyuridine (18F-5-FdUR), were examined regarding tissue distribution and tumor uptake in ascitic hepatoma AH109A-bearing rats. The differential absorption ratios of tumors of 18F-5-FUR, 18F-5-FU, and 18F-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 18F-5-FdUR were always 1.3–4 times higher than 18F-5-FU and 18F-5-FUR. We concluded that 18F-5-FdUR was a suitable radiopharmaceutical for tumor imaging. Positron emission tomography of a rabbit tumor located on the chest with 18F-5-FdUR clearly showed the tumor within 1 h.

Relationship between Recovery of Cell Surface Charge and Colony-forming Ability Following Radiation Damage in Three Cell-lines

SummaryAlterations in the negative surface charge after x-irradiation were investigated by cell electrophoresis in three different radiosensitive cell-lines: Burkitt lymphoma cells P3HR-1 (extrapolation number (n) = 1, D0 = 67 R), mouse mammary carcinoma cells FM3A (D0 = 150 R, n = 2·5), and mouse melanoma cells B16-C2W (D0 = 160 R n = 20). The electrophoretic mobility decreased with time after irradiation and reached a minimum 4 hours after exposure. The relationship between the decrease in mobility during 4 hours and the radiation dose was the same in three cell-lines and consisted of two straight lines. In Burkitt lymphoma cells, the decrease in mobility was irreversible, whereas the negative surface charge recovered after irradiation with 50 R in FM3A, and with doses up to 500 R in C2W. The surviving fractions (colony-forming ability) and the fractions of electrophoretically-recovered cells during 24 hours after exposure showed good correlation for five dose-points in C2W.

Stability of Cerebral Blood Flow and Oxygen Metabolism during Normal Aging

Cerebral blood flow and oxygen metabolism in aged normal subjects were measured with positron emission tomography and their relationship with brain atrophy was evaluated. Brain atrophy progressed in a linear fashion during aging while cerebral blood flow and oxygen metabolism were well preserved. The finding suggests that brain atrophy is an aging process less dependent on cerebral blood flow and metabolism over the course of normal aging.

Decrease in capillary growth during aging.

Abstract The rate of capillary growth during the wound-healing process was quantitatively measured in rat transparent chambers. The vascularization borders advanced into the wounded area at the rate of 0.18 mm/day in each of the three age groups of male Donryūrats: 5–weeks old, 8–9 weeks old, and 39–41 old. The rate decreased to 0.13 mm/day in the rats 59–80 weeks old. This decrease of the vascular growth rate in older animals was statistically significant (p