Hepatobiliary scintigraphy during cholestatic and noncholestatic periods in patients with progressive familial intrahepatic cholestasis after partial external biliary diversion.

BACKGROUND: The purpose of the study was to determine the distribution of excreted bile during cholestatic periods and in remission in patients with progressive familial intrahepatic cholestasis (PFIC) after surgery with partial external biliary diversion (PEBD), using hepatobiliary scintigraphy. METHODS: Using intravenously administered technetium Tc 99m-labeled mebrofenin, the distribution of bile during periods of biochemical cholestasis and in remission was investigated in patients with PFIC operated with PEBD. Stomal bile, urine, and feces from the patients were collected during 24 hours after administration of technetium Tc 99m-labeled mebrofenin; and the fractions of remaining radioactivity in the 3 compartments and the remaining isotopic activity in the body were quantified using scintigraphy. RESULTS: Nine patients (4 boys and 5 girls) were studied. The median age was 13 (range, 5-24) years, and they had been operated with PEBD at a median time of 10 (range, 4-14) years before entering the study. Thirteen scintigraphic examinations were analyzed: 8 during noncholestatic remission (n = 7 patients) and 5 during cholestasis (n = 3 patients). The patients studied during remission discharged a significantly larger fraction of isotopic activity through the stoma (median, 90% vs 22%; P < .05) and a significantly lower fraction through the urine (median, 2.5% vs 15%; P < .05) compared with the patients studied during cholestasis. CONCLUSION: Hepatobiliary scintigraphy could detect substantial differences in the output of bile. Further studies are needed to determine whether these differences may explain the mechanism of the PEBD operation or merely are secondary to the degree of cholestasis.

Blood pool scintigraphy of the skull in relation to head-down tilt provocation in patients with chronic tension-type headache and controls.

OBJECTIVE: To investigate the mechanisms behind the increase of chronic tension-type headache during head-down tilt. BACKGROUND: The pathophysiology of chronic tension-type headache is unknown. DESIGN AND METHODS: Ten patients suffering from chronic tension-type headache and 10 age- and sex-matched controls were studied with respect to pain intensity and alterations in cranial blood volume using planar scintigraphy and radiolabeled autologous erythrocytes before, during, and after head-down tilt, a procedure known to increase chronic tension-type headache. RESULTS: Four of 8 patients with chronic tension-type headache studied had increased cerebrospinal fluid pressure. During head-down tilt, the pain increased significantly in the group with chronic tension-type headache (P <.001) while the procedure did not cause headache in the controls. Blood volume significantly increased extracranially and decreased intracranially in both groups during head-down tilt. The extracranial nasal blood volume was significantly related to the pain experienced by the patients with chronic tension-type headache before and during head-down tilt. CONCLUSIONS: Although the changes in blood volume and, presumably, the increase of intracranial pressure were similar in the patients with chronic tension-type headache and the controls, only the patients experienced pain and pain increase during head-down tilt. This indicates that the pre-head-down tilt conditions must be different in the 2 groups and should be related to increased cerebrospinal fluid pressure/intracranial venous pressure in patients with chronic tension-type headache compared with controls. A difference in central mechanisms may, however, also be of importance for the difference in headache provocation in the 2 groups during head-down tilt.

[Scintigraphic assessment of the small intestine transit. Diagnostic investigation of dysmotility with 99mTc-HIDA]. / Skintigrafisk bestämning av passsagetid genom tunntarmen. Vägledande diagnostik med 99mTc-HIDA vid utredning av dysmotilitet.

Symptoms from the gastro-intestinal tract are common and often difficult to evaluate. Specialised examination techniques are available only at a limited number of clinics. A technique based on biliary scintigraphy when measuring the transit of contents through the small intestine has been developed. The investigation is simple to perform and convenient for the patient. It can be carried out at any clinic equipped with a gamma camera. 30 healthy individuals were examined in order to obtain reference values. 23 patients were examined with scintigraphy in combination with upper gastrointestinal manometry, 10 of whom had abdominal pain and neurogenic or myogenic pseudoobstruction disclosed by manometry. In another 4 patients, slow transit and pain prevailed in conjunction with normal manometric findings. Rapid transit and diarrhoea was found in 3 patients with various abberations on manometry. Of the remaining patients, 4 had slow transit and diarrhoea with intestinal neuropathy and pseudoobstruction, and 2 had slow transit along with endocrinopathies (diabetes, pituitary insufficiency).

Scintigraphy of the small intestine: a simplified standard for study of transit with reference to normal values.

Evaluation of small bowel transit, which should preferably be performed using non-invasive techniques, is complex owing to the anatomical position of the small bowel. In order to avoid any influence of the gastric emptying rate on scintigraphic results, we have used (99m)Tc-HIDA, an intravenous tracer that is excreted in bile and thereby delivered directly into the duodenum. Thirty healthy subjects were studied after an overnight fast. Immediately after administration of 120 MBq (99m)Tc-HIDA, dynamic 1-min image acquisitions were begun. The duodenum and caecum were easily identified on the digitised images. Small bowel transit time was determined from the difference in the arrival times of the radiopharmaceutical in the proximal duodenum and caecum, as assessed by evaluation of the count rate against background activity (Scint 1) and by the visual appearance of activity (Scint 2). Hydrogen breath test was performed simultaneously to evaluate scintigraphic transit. Scintigraphic transit tests were also performed in 23 patients with motility disorders who had undergone manometry of the small bowel. In healthy subjects, the transit time of (99m)Tc-HIDA was 77.9+/-31.1 min (Scint 1) or 79.3+/-30.9 min (Scint 2) and the lactulose transit time was 100.1+/-43.4 min. Seventeen of the 23 patients had a dysmotility pattern verified by manometry, and in 14 of these patients, (99m)Tc-HIDA transit was prolonged. (99m)Tc-HIDA small bowel transit is a readily available method for the detection of transit abnormalities in the clinical setting. The method is clinically feasible and the transit time of (99m)Tc-HIDA shows a good correlation with results of the hydrogen breath test (lactulose transit time) in healthy volunteers.

Dynamic 99Tcm-HIDA SPET: non-invasive measuring of intrahepatic bile flow. Description of the method and a study in primary sclerosing cholangitis.

In this study dynamic 99Tcm-HIDA single photon emission tomography (SPET) was performed in patients with primary sclerosing cholangitis and normal test subjects. The method offers the possibility of functional analysis of individual liver segments. After injection of 120 MBq of 99Tcm-HIDA, 12 consecutive SPET examinations were performed at 6-min intervals. The segmental borders of liver segments as seen on computed tomography or magnetic resonance examinations were superimposed on the scintigraphic images allowing placement of regions of interest (ROIs) in specific liver segments. Sampling from the same ROIs in consecutive SPET images enabled creation of time-activity curves for individual liver segments. A range of normal values was created by quantitative analysis of normal volunteer studies. Results of the studies in patients correlated well with cholangiographic extent of disease, liver function tests and histological stage. The technique may have particular value in diseases that affect the liver in a nonhomogenous or segmental fashion. Giving an indication of bile clearance from individual liver segments, it can quantify the functional importance of radiologically detected strictures. Percutaneous liver biopsy can be directed to the worst affected parts of the liver, making biopsy more representative. Sequential studies may allow monitoring of disease progression, aiding in selection and timing of therapeutic procedures.

Mapping pathological (99m)Tc-d,l-hexamethylpropylene amine oxime uptake in Alzheimer's disease and frontal lobe dementia with SPECT.

Seventeen patients with probable Alzheimer's disease (AD), 7 patients with frontal lobe dementia (FLD) and 19 control subjects (NOR) were examined by (99m)Tc-d,l- hexamethylpropylene amine oxime ((99m)Tc-HMPAO) SPECT. Images were standardised in the same 3D space and averaged within each group. After normalisation, the three sets of images were analysed in all cerebral lobes, hippocampus, thalamus and basal ganglia. In AD, the (99m)Tc-HMPAO uptake values were significantly reduced, as compared to NOR, in the parietal, temporal and insular lobes. In patients with FLD, the uptake was altered in all lobes with the exception of the parietal lobe. The uptake in the nucleus caudatus decreased significantly in both AD and FLD as compared to NOR. The uptake in the anterior cingulate cortex was significantly reduced in FLD. Subtraction images highlighted all significantly decreased areas. In conclusion, standardising SPECT in a common space and subtracting data from a control group improves the visual interpretation of images. In this study, the typical temporo-parietal and fronto-parietal (99m)Tc-HMPAO uptake reductions were found in AD and FLD, respectively. The uptake in the nucleus caudatus was found to decrease significantly in AD and FLD and the one in the anterior cingulate cortex was reduced in FLD.

SPET imaging of central muscarinic acetylcholine receptors with iodine-123 labelled E-IQNP and Z-IQNP.

1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP) is a muscarinic acetylcholine receptor (mAChR) antagonist and the racemic ligand contains eight stereoisomers. In a single-photon emission tomography (SPET) study in monkeys we recently confirmed that [123I]E-(R,R)-IQNP ([123I]E-IQNP) is a radioligand with modest selectivity for the M1 and M4 subtypes, whereas [123I]Z-(R,R)-IQNP ([123I]Z-IQNP) is non-subtype selective. In the present SPET study, E- and Z-IQNP were examined in human subjects. SPET examination was performed on three male subjects after i.v. injection of [123I]E-IQNP and in another three after i.v. injection of [123I]Z-IQNP. The binding potential (BP) for [123I]E-IQNP was calculated using several quantitative approaches with the cerebellum as a reference region. High-performance liquid chromatography was used to measure radioligand metabolism in plasma. Following [123I]E-IQNP, the radioactivity was high in the neocortex and striatum, intermediate in the thalamus and low in the pons and cerebellum, which is consistent with the rank order for the regional density of M1 and M4 subtypes in vitro. For all regions, peak equilibrium was identified within the 48-h data acquisition. The simplified reference tissue approach using SPET data from 0 to 48 h was the most reliable in this limited series of subjects. Following injection of [123I]Z-IQNP, radioactivity was high in the neocortex and striatum, intermediate in the thalamus and pons and low in the cerebellum, which is in agreement with the density of M1, M2 and M4 subtypes as measured in vitro. Quantitative analyses provided indirect support for specific M2 binding of Z-IQNP in the cerebellum. The high selectivity of [123I]E-IQNP for M1 and M4 receptors allowed the use of cerebellum as a reference region devoid of specific binding, and may be advantageous for applied clinical studies of M1 and M4 receptors binding in man. [123I]Z-IQNP has potential for exploration of M2 receptor binding in the cerebellum.

Z-IQNP: a potential radioligand for SPECT imaging of muscarinic acetylcholine receptors in Alzheimer's disease.

RATIONALE: The density of the M2 subtype of muscarinic acetylcholine receptors (mAChR) has been shown to be reduced in the brain of patients with Alzheimer's disease (AD). It is therefore of interest to develop a brain imaging method for diagnostic purposes. Z-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo1-propen-3-yl)-alpha-phenylacetat e (Z-IQNP) is a muscarinic antagonist with high affinity for the M2 subtype. OBJECTIVE: The pharmacological characteristics and topographic distribution of radiolabelled Z-IQNP as a radioligand for the M2 mAChR subtype were examined in vitro and in vivo. METHODS: Z-IQNP was labelled with 1251 and 123I. Autoradiography was performed on whole-hemisphere cryosections from human post mortem brains. SPECT was performed in a cynomolgus monkey. RESULTS: Autoradiography showed binding of [125I]Z-IQNP in all brain regions, which was inhibited by the non-selective muscarinic antagonist scopolamine. The addition of BIBN 99, a compound with high affinity for the M2 subtype, inhibited [125I]Z-IQNP binding particularly in the cerebellum, which has a high density of the M2 subtype. SPECT demonstrated high uptake of [123I]Z-IQNP in all brain regions. The binding was markedly reduced in all brain regions after pretreatment with the non-selective muscarinic antagonist dexetimide and also the M1 antagonist biperiden. Dexetimide markedly inhibited [123I]Z-IQNP binding in the cerebellum, which is consistent with a high density of M2-receptors in this region. The sigma receptor binding compound DuP 734 had no effect on Z-IQNP binding either in vitro or in vivo. CONCLUSIONS: This study indicates that radiolabelled Z-IQNP has high specificity for mAChR with higher affinity for the M2 than the M1 subtype and negligible affinity for sigma recognition sites both in vitro and in vivo. [123I]Z-IQNP should be useful for future SPECT studies in AD for examination of the density of M2 receptors particularly in the cerebellum.

Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M(1 )and M(2) muscarinic acetylcholine receptors in Alzheimer's disease.

Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z-IQNP) has high affinity to the M(1 )and M(2) muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[(123)I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[(123)I]IQNP binding in all these regions. The percentage of unchanged Z-[(123)I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[(123)I]IQNP showed higher uptake in M(2)-rich regions, compared with previously obtained results with E-[(123)I]IQNP. In conclusion, the radioactivity distribution from Z-[(123)I]IQNP in monkey brain indicates that Z-[(123)I]IQNP binds to the M(1)- and M(2)-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.

von Hippel-Lindau protein induces hypoxia-regulated arrest of tyrosine hydroxylase transcript elongation in pheochromocytoma cells.

Rat pheochromocytoma (PC12) cells were stably transfected with either wild type or mutated human von Hippel-Lindau tumor suppressor protein (hpVHL). These proteins have opposing effects on regulating expression of the gene encoding tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Whereas wild type hpVHL represses levels of TH mRNA and protein 5-fold, a truncated pVHL mutant, pVHL(1-115), induces accumulation of TH mRNA and protein 3-fold. hpVHL-induced inhibition of TH gene expression does not involve either a decrease in TH mRNA stability or repression of TH promoter activity. However, repression results from inhibition of RNA elongation at a downstream region of the TH gene. This elongation pause is accompanied by hpVHL sequestration in the nuclear extracts of elongins B and C, regulatory components of the transcription elongation heterotrimer SIII (elongin A/B/C). Hypoxia, a physiological stimulus for TH gene expression, alleviates the elongation block. A truncated pVHL mutant, pVHL(1-115), stimulates TH gene expression by increasing the efficiency of TH transcript elongation. This is the first report showing pVHL-dependent regulation of specific transcript elongation in vivo, as well as dominant negative activity of pVHL mutants in pheochromocytoma cells.

Influence of the phosphate balance on the activity distribution of 99mTc-hydroxy-methylene diphosphonate. Experimental studies in the mouse.

OBJECTIVE: The purpose was to determine whether changes in the phosphate balance have an influence on the distribution of bone-seeking radiopharmaceuticals. MATERIAL AND METHODS: The biodistribution of 99mTc-HDP in mice, intravenously administered under varying conditions, was assessed by removing different organs and estimating their activity in a scintillation counter. Some experiments were also performed with 99mTc-MDP and 99mTc-DPD. RESULTS: After 1 h and 18 h on phosphate-enriched drinking water, the mice showed a strongly increased uptake in all organs/tissues representing background activity and a decrease in the bone uptake. This pattern changed with time. After 6-8 days of phosphate load, we saw a more favourable distribution with a reduction of the background and whole-body activity. Administration of hPTH 1-34 gave rise to an activity distribution similar to that after 6-8 days on phosphate-enriched water. Changing the phosphate balance had less obvious effects on the distribution of 99mTc-MDP and 99mTc-DPD. CONCLUSION: The activity distribution of bone-seeking radiopharmaceuticals in the mouse is affected by the phosphate balance. The mechanism behind this finding is unknown but it may be partially mediated by PTH. It is possible that changes in the phosphate balance, induced by pharmaceuticals or by dietary changes, may affect the image quality at bone scintigraphy.

Evaluation and metabolite studies of 125I- and 123I-labelled E-(R,R)-IQNP: potential radioligands for visualization of M1 muscarinic acetylcholine receptors in brain.

A new ligand for the M1 muscarinic receptor subtype, E-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (E-IQNP), was labelled with 125I and 123I for autoradiographic studies on human whole-brain cryosections and SPET studies, respectively, in Cynomolgus monkey. Autoradiography demonstrated E-[125I]IQNP binding in M1 receptor-rich regions such as the neocortex and the striatum. The binding was displaceable by the selective M1 antagonist biperiden. In vivo single photon emission tomography (SPET) studies with E-[123I]IQNP demonstrated a high accumulation of radioactivity in the monkey neocortex. Rapid hydrolysis of the quinuclidinyl ester to the free acid was found to be a major biotransformation route for E-[123I]IQNP. The free acid of E-[123I]IQNP does not pass the blood-brain barrier, but the plasma concentration was high as compared to the total radioactivity in brain. It is thus necessary to correct for the high concentration of radioactive metabolites in parenchymal blood (CBV) to obtain accurate values for E-[123I]IQNP binding in brain.

Comparison between scintigraphy with polyclonal immunoglobulin (99Tcm-HIG) and physical examination in polyarthritic disease.

99Tcm-labelled polyclonal human immunoglobulin 99Tcm-HIG scintigraphy has been suggested as a technique to detect joint inflammation in arthritic disorders. Scintigraphy was performed in fifteen patients with active polyarthritis. All joints except the hips were scored clinically for swelling and pain by a rheumatologist and scintigraphic images were obtained at 30 minutes and four hours after injection of 350MBq 99Tcm-HIG. The images were assessed by a nuclear medicine physician according to a four grade scale. The images were easy to assess. There was a highly significant correlation between swelling and scan score, but no correlation between pain and scan score. The mechanism for the accumulation of activity to inflamed synovial tissue remains unclear. The mean values of the scan score however increased significantly between 30 minutes and 4 hours, indicating an active binding mechanism. The method has a potential as an objective tool in monitoring rheumatic diseases.

Preoperative gastric emptying. Effects of anxiety and oral carbohydrate administration.

BACKGROUND: Overnight fasting is routine before elective surgery. This may not be the optimal way to prepare for surgical stress, however, because intravenous carbohydrate supplementation instead of fasting has recently been shown to reduce postoperative insulin resistance. In the current study, gastric emptying of a carbohydrate-rich drink was investigated before elective surgery and in a control situation. METHODS: Twelve patients scheduled for elective surgery were randomly given 400 mL of either a carbohydrate-rich drink (285 mOsm/kg, 12.0% carbohydrates, n = 6) or water 4 hours before being anesthetized. Gastric emptying was measured (gamma camera, 99Tcm). Each patient repeated the protocol postoperatively as a control. All values were presented as the mean +/- SEM by means of a nonparametric statistical evaluation. RESULTS: Despite the increased anxiety experienced by patients before surgery (p < 0.005), gastric emptying did not differ between the experimental and control situations. Initially, water emptied more rapidly than carbohydrate. However, after 90 minutes, the stomach was emptied regardless of the solution administered (3.2 +/- 1.1% [mean +/- SEM] remaining in the stomach in the carbohydrate group versus 2.3 +/- 1.2% remaining in the stomach in the water group). CONCLUSIONS: Preoperative anxiety does not prolong gastric emptying. The stomach had been emptied 90 minutes after ingestion of both the carbohydrate-rick drink and water, thereby indicating the possibility of allowing an intake of iso-osmolar carbohydrate-rich fluids before surgery.

In vivo dynamical distribution of 131I-VIP in the rat studied by gamma-camera.

The in vivo distribution of vasoactive intestinal peptide (VIP) was studied for the first time using a rat model in combination with labeled VIP (131I-VIP) and a gamma-camera. A dynamic scan showed that 131I-VIP was cleared rapidly from the blood circulation. The radioactivity was taken up and accumulated in the lungs during the first minute. During the next 15 min, the radioactivity was slowly removed from the lungs and redistributed into the kidneys, gastric mucosa, liver and small intestine. However, the radioactivity extracted by the lungs was about 6-fold lower during the first minute when a large amount of the non iodinated VIP was coinjected with the 131I-VIP. 131I-VIP was eliminated rapidly from the blood with a half-life of 0.44 +/- 0.05 (min +/- SD) while in lung the elimination half-life was determined to 2.3 +/- 0.8 (min +/- SD). Of the radioactivity in the lungs, 2% was found to be intact 131I-VIP after 20 min. In all other organs the radioactivity found was assumed to be low molecular weight fragments of 131I-VIP. We suggest that lungs play an important role to extract VIP from the circulation after an i.v. administration. 131I-VIP degradation products are redistributed mostly to the kidneys and to the gastric mucosa to be excreted through urine and stomach contents, respectively.

Disturbances of fluid balance reduce the image quality of bone scintigraphy. Experimental studies in mice.

The effects of hydration, dehydration and osmotic diuresis on the activity distribution of bone-seeking radiopharmaceuticals have been studied in an experimental mouse system. It was found that any change of the water balance impairs the activity distribution of the radiolabelled phosphonate in the potential bone scintigraphic image. The findings suggest that in order to maintain image quality, elderly patients should not be instructed to drink a large volume of fluid after the administration of a bone-seeking radiopharmaceutical. Further investigations, though, have to be performed in humans.

Can pharmacological intervention improve the visualization of the reticuloendothelial system using 99mTc-labeled albumin nanocolloid to that achievable with 111In-labeled granulocytes? Experimental studies in mice.

The use of 99mTc-colloids for bone marrow scintigraphy is limited by a high liver uptake, which hampers the evaluation of surrounding skeletal structures. In an experimental mouse system, different measures to increase the bone marrow activity in relation to the liver activity have been tested. A slightly positive, but significant, outcome was achieved by three different measures, namely fasting, pretreatment with a calcium-blocking pharmaceutical (Nimodipine) and pretreatment with large amounts of a gelatine colloid. It is concluded that the possibilities of dramatically improving the bone marrow uptake of a colloid compared to the liver are limited and not comparable to that achievable using radiolabeled granulocytes.

Uptake of [131I]thiouracil in tumours of patients with disseminated malignant melanoma. A pilot study.

Previous studies on mice carrying melanoma have shown that 5-iodo-2-thiouracil (ITU) is accumulated in the tumours due to its specific incorporation into melanin during its synthesis. ITU is also selectively localized in murine melanoma metastases and in cultured human melanoma cells. Progressive formation of melanin is, however, a prerequisite for the incorporation. Four patients with disseminated melanoma were injected intravenously with 39-62 MBq [131I]TU. Blood and urine samples were gradually collected, and 3-7 days postinjection tumours were biopsied and examined by impulse counting. The patients were scanned with a gamma camera over the total body daily for 3-4 days. The radioactivity was rapidly excreted. Poor melanin pigmentation of the tumours and low proliferation rate (possibly induced by chemotherapy) decreased the uptake of radioactivity by the tumors, and no imaging was possible. One of the patients, however, had clearly progressive disease with darkly pigmented metastases which contained considerably higher levels of radioactivity than the surrounding skin. Calculations indicated that a doubling of the radioiodine dose would probably make visualization of the tumours possible.

Vesicoureteral reflux in adults studied by computerized radionuclide cystography.

Direct radionuclide cystography in a computerized method as described by Willi and Treves was used in adults with recurrent pyelitis but without evidence of obstruction. Reflux was observed in 15 out of 38 patients. In patients with neurogenic bladder dysfunction or megaureters, reflux began early during the bladder filling and attained higher volumes than in those with uncomplicated pyelitis, who had minor reflux appearing mainly during voiding. Bladder capacity and detrusor compliance were lower in patients with reflux than in those without reflux. The low radiation exposure in radionuclide cystography permits observation of the urodynamic course of urinary reflux and correlation to the intravesical volume and pressure. The method is sensitive, and minor refluxed volumes can be detected. Radionuclide cystography can therefore be recommended for checking of surgical results and for follow-up of patients with neurogenic bladder dysfunction.

Effect of size fractionation on the distribution of an albumin colloid in the reticuloendothelial system of the mouse.

To study if by varying the particle size of a 99mTc albumin colloid preparation its relative bone marrow accumulation could be increased, it was separated by gel filtration and different fractions were injected into mice. Particles around and smaller than the peak size of the colloid, 31 nm, exhibited a higher bone marrow/liver-spleen uptake ratio than larger particles but the uptake ratio was similar to that of the unseparated colloid. An antimony sulphide colloid showed a similar particle size distribution, but the corresponding uptake ratio was half of the albumin colloid. This indicates that characteristics other than size determine the distribution of a colloid in the reticuloendothelial system.