Changes of the blood lymphocyte population following 131I treatment for nodular goiter.

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goiter. The patients received one to three doses of 300-550 MBq of 131I administered at 1 week intervals. Lymphocyte counts were significantly reduced both 1 and 6 weeks after treatment. This reduction was accompanied by a changed composition of the lymphocyte population. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming) was significantly reduced 1 and 6 weeks after 131I-administration. At 6 weeks there was a slight but statistically significant increase of the frequency of T-cells as identified by Leu 1 monoclonal antibodies. This was largely caused by an increased proportion of helper/induced T-cells as identified by Leu 3a monoclonals. 131I-treatment also reduced the capacity of lymphocytes to secrete immunoglobulins (Ig) upon PWM-stimulation. The most pronounced effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with PHA and ConA were not significantly changed. We conclude that these changes observed, with the exception of mitogen reactivity, are essentially similar to those occurring after external radiation therapy for cancer. We speculate that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by emitted beta-particles.

A new method for granulocyte labeling with technetium-99m: preliminary results in abscess detection.

A new method for 99mTc-labeling of granulocytes for clinical routine use has been developed. The labeling is simple to perform by means of a kit of radiopharmaceutical quality, utilizing dihydroxy-benzoic acid. Pretinning techniques are avoided. The technique has been applied clinically in 15 patients with indications of intra-abdominal abscess. In six patients, [99mTc]granulocyte scintigraphy at 3 hr and/or 24 hr after i.v. administration, correctly depicted the abscess, as verified by subsequent surgery. In the remaining patients, who were negative at surgery or recovered without operation, all scans were negative.

A special cut-off gamma camera for high-resolution SPECT of the head.

A modern system for single photon emission computerized tomography has been modified in order to optimize examinations of the head. By cutting off part of the detector housing and collimators at one edge, it is possible to rotate the camera close to the skull while still covering the entire brain and the skull base. The minimum radius of revolution used in 32 patients was thereby reduced from about 20 cm to 12.7 +/- 0.8 cm. This, combined with an adjustment of the 64 X 64 matrix to a 26- by 26-cm field of view, resulted in an improvement of the spatial resolution from about 19 mm to 12.6 +/- 0.3 mm with a low-energy, all-purpose collimator, and to 10.4 +/- 0.3 mm (FWHM) with a low-energy, high-resolution collimator. The improved spatial resolution offers several clinical advantages in studies of the brain, the cerebrospinal fluid space, and the skull base.

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.

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.

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.

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.

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.

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.

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.

[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).

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.

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.

Build-up effects at air cavities measured with thin thermoluminescent dosimeters.

The build-up and build-down situation around air cavities of various size in a polystyrene phantom was evaluated by measurements with LiF-Teflon disks with a thickness of about 1.6 X 10(-2) kg/m2. The measurements demonstrate that when irradiating with two opposed beams the surface dose at the cavity (depth 39 mm) is 74% of the maximum dose for 60 Co, 77% for 6 MV and 87% for 42 MV roentgen radiation.

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.

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.

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.

Effect of 32P treatment for polycythaemia vera on blood lymphocyte subpopulations and their functions.

The influence of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were severely impaired. Following a single oral dose of 32P (150-305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. 32P treatment sharply increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.

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.

Increased blood clearance rate of indium-111 oxine-labeled autologous CD4+ blood cells in untreated patients with Hodgkin's disease.

Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor.