Regional coupling of blood flow and methionine uptake in an experimental tumor assessed with autoradiography

Regional distribution of L-[methyl-¹⁴C] methionine (¹⁴C-MET) and 4-[¹⁸F] fluoro-antipyrine was compared using experimental rat tumors (AH109A) and a computerized autoradiogram image processor. Tissue distributions of the two tracers were found to be inhomogeneous in the tumor with nearly identical image patterns. Analysis of tissue radioactivities revealed that 82% of ¹⁴C-MET was derived from the acid insoluble fraction at 60 min after injection. The present study showed that ¹⁴C-MET uptake closely relates to tissue blood flow and may depend on its blood to tissue transport. Rapid incorporation of MET in the acid insoluble fraction implies that it is rapidly metabolized after transport into tumor tissue.     

Sleep disturbances in Japanese patients with Parkinson's disease--comparing with patients in the UK

Sleep disorders are common in the general population and occur more frequently with advancing age. However, patients with Parkinson's disease (PD) have been known to have various sleep disturbances beyond those to be expected from the effect of aging alone. We tried to quantify the various aspects of nocturnal sleep problems in PD using the PD sleep scale (PDSS). 64 patients with PD and 60 age- and sex-matched controls completed the PDSS. After neurological examinations, we assessed the degree of sleep disorder by the PDSS. We evaluated the severity of PD by the Hoehn and Yahr Scale and the unified PD rating scale (UPDRS). To compare the various aspects of nocturnal sleep problems in PD between in Japan and in the United Kingdom (UK), we referenced and compared our results with those by Chaudhui et al. The PDSS scores in PD group were significantly different from those in controls. Individual items of the scale showed good discriminatory power between PD and controls. Overall tendencies were the same in Japan and in the UK, but there were some different points, especially absence of refreshing quality of sleep in Japan. We believe that the PDSS provides an objective method for targeted therapeutic approaches for the treatment of disturbed sleep in PD even among countries with different cultures, such as Japan and the UK.     

An Evaluation of Polymethylmethacrylate Plasma Separator by Animal Experiment

Guest Editor's Introduction: This paper was presented at the first plasmapheresis symposium organized by the International Society for Artificial Organs and the International Center for Artificial Organs and Transplantation on April 3, 1982, Cleveland, Ohio. This paper was printed in the proceedings of this symposium: Plasmapheresis: Therapeutic Application and New Technologies, edited by Y. Nosé and PS Malchesky, JW Smith, and RS Krakauer, Raven Press, New York, 1983, p. 93–98. This is the first technical paper on the polymethylmethacryate (PMMA) plasma separator manufactured by Toray Medical Inc., Tokyo, Japan. The PMMA membranes had already been utilized as hemodialysis membranes. This paper deals with the PMMA hollow fiber plasma separator from its efficiency to filtrate plasma and for blood compatibility.     

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.     

Effect of simultaneous insertion of oleaginous base on the absorption and on the anticonvulsant effect of diazepam suppository

To clarify the drug-base interaction between diazepam (DZP) suppository and oleaginous base, we investigated the effect of simultaneous combination of oleaginous base on the absorption and on the anticonvulsant effect of DZP Suppository in rats. Simultaneous insertion of DZP suppository and oleaginous base significantly decreased maximum concentration (C(max)) and area under the blood concentration-time curve (AUC) of plasma DZP concentrations. Administration of DZP suppositories (2.5, 5 mg/kg) dose-dependently suppressed the pentylenetetrazol (PTZ)-induced seizures, and the anticonvulsant effect of DZP suppository (5 mg/kg) was reduced by simultaneous insertion of oleaginous base. In an in vitro study using a suppository release apparatus, simultaneous combination of DZP suppository and oleaginous base (1.5-98 mg) significantly decreased the accumulative release of DZP in a dose-dependent manner. These results suggested that when DZP suppository and oleaginous base are inserted simultaneously, the released DZP distributes partially to the oleaginous base, and this phenomenon is related to the decreases in the plasma concentration and the anticonvulsant effect of DZP.     

Error analysis of measured cerebral vascular response to acetazolamide stress by I-123-IMP autoradiographic method with single photon emission computed tomography: Errors due to distribution volume of I-123-IMP

OBJECTIVES: Iodine-123 (123I)-labeled N-isopropyl-p-iodoamphetamine (IMP) has been used as a cerebral blood flow (CBF) tracer for single-photon emission computed tomography (SPECT), and measurements of the CBF response to acetazolamide stress by SPECT with IMP are widely used to assess cerebral vascular reserve. To quantitate CBF by means of SPECT with IMP, an autoradiographic (ARG) method has been developed and is widely used. In the ARG method, CBF is calculated from the brain counts of the SPECT scan with an assumed distribution volume value of IMP (Vd). However, differences between true Vd and assumed Vd results in errors in calculated CBF. In the present study, errors in the CBF response to acetazolamide stress as calculated by the ARG method were investigated. METHODS: SPECT studies were performed on 12 patients with steno-occlusive lesions of the major cerebral artery. Two studies were performed on separate days. The first study was performed at rest (baseline), and the second during acetazolamide stress. SPECT scans were performed at 40 min (early scan) and 180 min (delayed scan) after intravenous injection of IMP. RESULTS: Although a simulation study showed that errors in calculated changes in CBF in response to acetazolamide stress, which result from differences between the true Vd and the assumed Vd, were larger when the baseline CBF and change in CBF were larger, values calculated by the ARG method with an assumed Vd were in good agreement with those calculated with true Vd obtained from early and delayed scan data. CONCLUSION: These data indicate that errors in the calculated CBF response to acetazolamide stress as calculated by the ARG method are negligible even at high CBF responses. The ARG method is therefore reliable for measurement of CBF response to acetazolamide stress.     

Apparent CBF decrease with normal aging due to partial volume effects: MR-based partial volume correction on CBF SPECT

Several studies using single photon emission tomography (SPECT) have shown changes in cerebral blood flow (CBF) with age, which were associated with partial volume effects by some authors. Some studies have also demonstrated gender-related differences in CBF. The present study aimed to examine age and gender effects on CBF SPECT images obtained using the 99mTc-ethyl cysteinate dimer and a SPECT scanner, before and after partial volume correction (PVC) using magnetic resonance (MR) imaging. Forty-four healthy subjects (29 males and 15 females; age range, 27-64 y; mean age, 50.0 +/- 9.8 y) participated. Each MR image was segmented to yield grey and white matter images and coregistered to a corresponding SPECT image, followed by convolution to approximate the SPECT spatial resolution. PVC-SPECT images were produced using the convoluted grey matter MR (GM-MR) and white matter MR images. The age and gender effects were assessed using SPM99. Decreases with age were detected in the anterolateral prefrontal cortex and in areas along the lateral sulcus and the lateral ventricle, bilaterally, in the GM-MR images and the SPECT images. In the PVC-SPECT images, decreases in CBF in the lateral prefrontal cortex lost their statistical significance. Decreases in CBF with age found along the lateral sulcus and the lateral ventricle, on the other hand, remained statistically significant, but observation of the spatially normalized MR images suggests that these findings are associated with the dilatation of the lateral sulcus and lateral ventricle, which was not completely compensated for by the spatial normalization procedure. Our present study demonstrated that age effects on CBF in healthy subjects could reflect morphological differences with age in grey matter.     

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry

OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.     

Regional differences between <Superscript>99m</Superscript>Tc-ECD and <Superscript>99m</Superscript>Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether ^99mTc-HMPAO or ^99mTc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8±6.6 years) were assigned to ^99mTc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6±6.7 years) to ^99mTc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq ^99mTc-HMPAO or ^99mTc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether ^99mTc-HMPAO and ^99mTc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.