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A computer controlled automated dispensor for the eluting, calibrating and dispensing of 99Tcm-pertechnetate.

This paper describes an automated 99Tcm-Dispensor, a computer controlled device for the programmed, automated elution of 99Tcm-sodium pertechnetate, its calibration, metered delivery and dilution. The elution can be programmed up to 7 days in advance. The total radioactivity of the eluate is assayed by a semiconductor counter integrated in the shielding of the pertechnetate reservoir. The volume of eluate actually available for dispensing is measured by capacitance and is monitored continuously. The specific concentration is calculated from total activity and volume, and is corrected for decay prior to each delivery. All activity bearing sections are shielded by lead-antimony covers specified to attenuate the radiation from generators up to 2 Ci 99Mo/99Tcm. The labelling vials are inserted into the dispensing chamber within a shielding vessel manually. The sodium pertechnetate solution is dispensed prior to the optional additional delivery of normal saline. The Tc-Dispensor maintains sterility, guards against accidental radioactive contamination, and is suited to reduce the radiation burden of personnel. All operations are recorded by the computer enabling the print-out of protocols. We found the Tc-Dispensor safe, precise and accurate.

Calibration↗

Differentiation of Charcot joint from osteomyelitis through dynamic bone imaging.

The bone scans of 25 patients with a clinical diagnosis of diabetic osteoarthropathy (Charcot joint) of the ankle and foot were analysed using the technique of dynamic bone imaging. The analysis of time-activity curves generated over the Charcot joint, the contralateral joint and the bone above the Charcot joint, produces characteristic patterns that are distinguishable from the ones observed for osteomyelitis. Recently it has been shown that the significance of dynamic bone imaging resides in its correlation to physiological and morphological components of bone. The difference in the blood supply to the long bones has been suggested as an explanation for the difference in time-activity curve patterns.

Arthropathy, Neurogenic↗

Diagnostic evaluation of adult polycystic kidney disease in childhood.

Since adult polycystic kidney disease, an autosomal-dominant disease, results in renal failure in at least 50% of affected patients, its detection before childbearing age is desirable. To evaluate this capability and the preferred screening technique, 28 members of two generations of an affected kindred were studied. Sonograms, excretory urograms with nephrotomograms, and clinical laboratory evaluation were compared. Five of six studied members of the older generation had cysts demonstrated by both sonograms and excretory urograms with nephrotomograms. Eleven of 22 members of the younger generation were affected, the youngest being 5 years old. In this group, excretory urograms with nephrotomograms were a slightly more sensitive detector, especially in the younger patients. However, sonography provided sufficient sensitivity in the older child, and, because of its noninvasive nature, was the preferred screening technique. The clinical laboratory evaluation was of little diagnostic aid in children with adult-type polycystic disease.

Adolescent↗

A novel bifunctional metabolizable linker for the conjugation of antibodies with radionuclides.

A novel heterogeneous bifunctional reagent containing an ester bond, N-[[4-(2-maleimidoethoxy)-succinyl]oxy]succinimide (MESS), was designed and synthesized for the conjugation of antibodies with the gallium-67 (67Ga) chelate of succinyldeferoxamine (SDF) via the ester bond. MESS was synthesized by the acylation of N-(2-hydroxyethyl)maleimide with succinic anhydride, followed by the activation of the resulting carboxylic acid to a succinimido ester. MESS possesses a maleimide group for protein conjugation and an active ester group for deferoxamine (DFO) coupling, and the two functional groups are linked via ester bonding. Conjugation of 67Ga-SDF with nonspecific human IgG was performed by reacting freshly thiolated IgG with the reaction product of MESS and DFO, followed by 67Ga labeling of the resulting conjugate using GaCl3 (67Ga-DFO-MESS-IgG). For comparison, 67Ga-DFO conjugated nonspecific human IgG with a nonmetabolizable linkage was synthesized under the same conjugation conditions as those for 67Ga-DFO-MESS-IgG, using a nonmetabolizable heterogenous bifunctional reagent [N-[(6-maleimidocaproyl)oxy]succinimide, EMCS] instead of MESS (67Ga-DFO-EMCS-IgG). HPLC size-exclusion chromatography of both preparations showed a single radioactivity and UV peak corresponding to the intact IgG. Generation of 67Ga-SDF from the 67Ga-DFO-MESS-IgG was demonstrated by reverse-phase HPLC analysis and cellulose acetate electrophoresis after the incubation of 67Ga-DFO-MESS-IgG in a buffered solution containing carboxyesterase. After injection of 67Ga-DFO-MESS-IgG into mice, faster radioactivity clearance from the blood and less radioactivity accumulation in the liver, kidney, and spleen was noted than when 67Ga-DFO-EMCS-IgG was injected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of four radiopharmaceuticals for imaging inflammation in a rabbit model of arthritis.

We compared the utility of four radiopharmaceuticals; 111In-chloride, 67Ga-citrate, 111In labeled leukocytes (WBCs) and 99mTc-MDP for assessing the inflammatory response in antigen induced arthritis in a rabbit model. A total of 20 rabbits, divided into four equal groups, were included in this study. Each group was studied twice with a single radiotracer; a baseline study and a follow-up study after induction of the arthritis. Knee to knee, knee to whole body, and knee to liver (except for the group studied with 99mTc-MDP) ratios were generated. Knee to knee ratios showed no significant change from baseline to arthritis studies in any of the four groups. Significantly increased knee to total body ratios were seen in all of the groups, except for the group studied with 99mTc-MDP. The greatest increase was seen in the group studied with 111In-chloride. Significantly increased knee to liver ratios were observed in all three groups for which these ratios were generated and again the greatest increase was observed in the group studied with 111In-chloride. In summary, based on the higher uptake observed in this group, of the four radiotracers evaluated, 111In-chloride is probably the most useful for monitoring the inflammatory response in antigen induced arthritis. The symmetry of the response suggests that it may also be useful in monitoring the response to therapy.

Animals↗

Diffusion tensor MR imaging of principal directions: a tensor tomography approach.

A novel approach to reconstructing the principal directions of a diffusion tensor field directly from magnetic resonance imaging (MRI) data using a tensor tomography data acquisition approach was developed. If tensor eigenvalues are assumed to be known, the reconstruction of principal directions requires fewer measurements than the reconstruction of the full tensor field. The tensor tomography data acquisition method (rotating diffusion gradients) leads to a unique reconstruction of principal directions, whereas the conventional MRI acquisition technique (stationary diffusion gradients) leads to an ambiguous reconstruction of principal directions when the same number of measurements are used. A computer-generated phantom was used to simulate the diffusion tensor field in the mid-ventricular region of the myocardium. The principal directions of the diffusion tensor field were assumed to align with the fibre structure of the myocardium. An iterative algorithm was used to reconstruct the principal directions. Computer simulations verify that the proposed method provides accurate reconstruction of the principal directions of a diffusion tensor field.

Algorithms↗

The relationship between observations and measures of oral and pharyngeal residue from videofluorography and scintigraphy.

We examined measures of oral and pharyngeal residues from scintigraphic studies and estimates/observations from videofluorographic (modified barium swallow) studies taken on the same day but not concurrently in 16 dysphagic patients of varying etiologies presenting with oral and/or pharyngeal dysphagia. Oral and pharyngeal residuals following the swallow were quantified scintigraphically and were then compared with measures of residuals obtained from the modified barium swallow. Estimates of oral and pharyngeal residues from the modified barium swallows were generated by a trained observer who was blinded to the scintigraphic data. Positive and significant Spearman correlations between oral and pharyngeal residue measures from scintigraphy and observations of oral and pharyngeal residues from modified barium swallows were found. This supports the validity of observations of oral and pharyngeal residues in clinical studies. Limitations of these observations are discussed.

Aged↗

Tracer kinetic modeling approaches for the quantification of hepatic function with technetium-99m DISIDA and scintigraphy.

Serial scintigraphic images following injection of [99mTc]iminodiacetic acid compounds such as [99mTc]diisopropyl-iminodiacetic acid (DISIDA) provide qualitative information about liver function. We have investigated approaches for quantitatively describing liver function in terms of the kinetics of DISIDA extraction and excretion by the liver. Several compartmental model configurations were evaluated. A three-compartment model (blood, hepatic parenchyma, intrahepatic bile) was found to fit the data best and was used in conjunction with dynamic image data to obtain estimates of rate constants for liver extraction and excretion of DISIDA, and mean residence time (MRT) of DISIDA in the liver. A noncompartmental approach based on a parametric deconvolution technique was also used to estimate the noncompartmental mean residence time (MRTnc). To assess limitations of the noncompartmental approach, computer simulations were performed using the three-compartment model to generate time-activity curves followed by analysis of these curves by the noncompartmental method. The effect of plasma total bilirubin level on DISIDA uptake and MRT was also investigated. These techniques are readily adaptable to standard nuclear medicine computing facilities, and could be used in the clinical setting to numerically describe serial DISIDA studies (especially in liver transplant patients) efficiently and noninvasively.

Adult↗

Scintillation camera imaging with I-123.

Iodine-123 produced from three different nuclear targets (Te-122, Te-124, and I-127) was evaluated for spatial resolution and sensitivity with an Anger scintillation camera. Te-122 targets generated a substantial amount of I-130, which necessitated use of a medium-energy collimator. Te-124 targets produced solutions with significant amounts of I-124. Shortly after the end of bombardment, a 4,000-hole (4KH) collimator was satisfactory; at 30 hours, a medium-energy collimator was required. High-purity I-123 from an I-127 target gave excellent spatial resolution when the 4KH collimator was used, but low-energy "foil" collimators were not adequate.

Aluminum↗

[The problem of induced genome instability as the basis of the increased morbidity in children exposed to low-intensity radiation at low doses].

The main results of the complex examination of the genome instability are presented in children constantly living on territories contaminated with radionuclides as a result of the accident at the CNPP (Novozybkov district, Bryansk region, 16-18 Ci/km2, 137Cs) and in children exposed to low-intensity radiation at different stages of ontogenetic development: children exposed to postnatal irradiation in 1986 (born before the accident), children exposed to intrauterine irradiation during the accident in 1986, children of irradiated parents born after the accident in 1987-1992 and in 1994-2000. In all examined groups of irradiated children increased frequencies of certain radiation-induced chromosome aberrations were observed as well as a reduced activity of unscheduled synthesis of genomic DNA in lymphocytes and peculiarities in individual heterozygosity of genes encoding structural and enzymatic proteins of blood. An increased radiosensitivity of lymphocyte genomes to testing in vitro irradiation and peculiarities in the dynamics of the frequencies of chromosome aberrations and sister chromatid exchanges in 3 cell generations were revealed in children from the contaminated areas. The data obtained suggest a systemic character of dysgenomic effects, the reality of induction of genome instability in the growing organism of children exposed to low-intensity radiation at low doses the expression of which is determined by individual genotypic features of the organism. Biological significance of the phenomenon of the post-radiation genome instability, its relation to the state of health and the pathogenetic role in the development of somatic pathology are postulated.

Adolescent↗

Effects of extracellular acetylcholine on muscarinic receptor binding assessed by [125I]dexetimide and a simple probe.

New pharmacologic approaches to enhance brain cholinergic function focus on increasing intrasynaptic acetylcholine. We examined the usefulness of a simple probe and [125I]dexetimide to evaluate in vivo the effects of extracellular acetylcholine on muscarinic receptor binding in the mouse brain. After radiotracer injection continuous time/activity curves were generated over 330 min. [125I]Dexetimide reached a plateau at 90 min post-injection. To increase extracellular acetylcholine, the anticholinesterase physostigmine was administered at 120 min, producing a reversible decrease in [125I]dexetimide specific binding (23%) for 30 min. These findings demonstrate that dynamic changes in extracellular acetylcholine can be evaluated by displacement of [125I]dexetimide binding in vivo using a simple probe system.

Acetylcholine↗

New radiolabeled CCK-8 analogues [Tc-99m-GH-CCK-8 and Tc-99m-DTPA-CCK-8]: preparation and biodistribution studies in rats and rabbits.

The aim of this study is to label CCK-8 with Tc-99m and to investigate its radiopharmaceutical potential. CCK-8 was labeled with Tc-99m using GH and DTPA as bifunctional chelating agents. Labeling efficiency was higher than 99%. Complex was stable more than 5 hours at room temperature. 37 MBq Tc-99m-GH-CCK-8 or Tc-99m-DTPA-CCK-8 was administered intravenously to rabbits for biodistribution experiments. Dynamic and static images were obtained from anterior projection using a Camstar XC/T gamma camera. For quantitative evaluation, regions of interest were drawn on organs and time-activity curves were generated. The highest accumulation occurred in brain within 10 and 30 minutes after injection. Renal and hepatobiliary excretion were observed. Brain distribution studies in rats showed the highest activity was in hypothalamus. Results demonstrated that Tc-99m-GH-CCK-8 and Tc-99m-DTPA-CCK-8 analogs may be a useful new class of receptor-binding peptides for diagnosis and therapy of brain diseases related with CCK-B receptor-expressing tumors.

Animals↗

Detection of amyloid plaques by radioligands for Abeta40 and Abeta42: potential imaging agents in Alzheimer's patients.

Alzheimer s disease (AD) is linked to increased brain deposition of amyloid-beta (Abeta) peptides in senile plaques (SPs), and recent therapeutic efforts have focused on inhibiting the production or enhancing the clearance of Abeta in brain. However, it has not been possible to measure the burden of SPs or assess the effect of potential therapies on brain Abeta levels in patients. Toward that end, we have developed a novel radioligand, [(125)I]TZDM, which binds Abeta fibrils with high affinity, crosses the blood-brain barrier (BBB), and labels amyloid plaques in vivo. Compared to a styrylbenzene probe, [(125)I]IMSB, [(125)I]TZDM showed a 10-fold greater brain penetration and labeled plaques with higher sensitivity for in vivo imaging. However, this ligand also labels white matter, which contributes to undesirable high background regions of the brain. Interestingly, parallel to their differential binding characteristics onto fibrils composed of 40 (Abeta40)- or 42 (Abeta42)-amino-acid-long forms of Abeta peptides, these radioligands displayed differential labeling of SPs in AD brain sections under our experimental conditions. It was observed that [(125)I]IMSB labeled SPs containing Abeta40, amyloid angiopathy (AA), and neurofibrillary tangles, whereas [(125)I]TZDM detected only SPs and Abeta42-positive AA. Since increased production and deposition of Abeta42 relative to Abeta40 may be crucial for the generation of SPs, [(125)I]TZDM and related derivatives may be more attractive probes for in vivo plaque labeling. Further structural modifications of TZDM to lower the background labeling will be needed to optimize the plaque-labeling property.

Alzheimer Disease↗

99mTc-interleukin-2 and (99m)Tc-HMPAO granulocyte scintigraphy in patients with inactive Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease that may involve the whole gut. Marked intestinal T cell and macrophage activation is a key feature of the disease. Polymorphonuclear cell infiltration is also observed in the diseased gut, mainly during active inflammation. Scintigraphic detection of granulocytes and activated lymphocytes infiltrating the gut wall may be useful in identifying a subgroup of patients with clinically inactive CD who are undergoing early clinical relapse. The aims of the present study were (a) to compare the effectiveness of scintigraphy with (99m)Tc-labelled interleukin-2 ((99m)Tc-IL2) and with (99m)Tc-HMPAO labelled granulocytes ((99m)Tc-WBC) in detecting the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months) and (b) to assess the accuracy of these techniques in predicting future disease relapse. We studied 29 patients with ileal and/or colonic CD in stable clinical remission (Crohn's Disease Activity Index <150 for at least 12 months) using both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy in order to evaluate the extent of acute and chronic inflammation in the bowel. Planar and single-photon emission tomography images were acquired in each patient at 1 h p.i. For quantitative analysis of (99m)Tc-IL2 uptake, the abdomen was divided into 32 regions of interest. Despite the absence of symptoms, 18 patients (62%) showed a positive (99m)Tc-IL2 and 18 (62%) a positive (99m)Tc-WBC scan. Only 12 patients (41.4% of the total group) were positive on both scans, and the sites of IL2 and granulocyte bowel uptake were usually located in different segments, indicating that in CD, acute and chronic inflammation can be present in different sites. As far as the prognostic role of the two scans in predicting future disease relapse is concerned, both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy showed a high negative predictive value (1.00 and 0.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves generated between scintigraphic findings and time free from disease relapse were statistically different only for (99m)Tc-IL2 scintigraphy (log-rank test, P=0.013). These results indicate that (99m)Tc-IL2 scintigraphy can be useful in selecting CD patients in clinical remission who could benefit from preventive therapy to avoid disease relapse.

Crohn Disease↗

Bioaccumulation of nickel by intercalation into polycrystalline hydrogen uranyl phosphate deposited via an enzymatic mechanism.

A Citrobacter sp. accumulates uranyl ion (UO2(2+)) as crystalline HUO2PO4.4H2O (HUP), using enzymatically generated inorganic phosphate. Ni was not removed by this mechanism, but cells already loaded with HUP removed Ni2+ by intercalative ion-exchange, forming Ni(UO2PO4)2.7H2O, as concluded by x-ray diffraction (XRD) and proton induced x-ray emission (PIXE) analyses. The loaded biomass became saturated with Ni rapidly, with a molar ratio of Ni:U in the cellbound deposit of approx. 1:6; Ni penetration was probably surface-localized. Cochallenge of the cells with Ni2+ and UO2(2+), and glycerol 2-phosphate (phosphate donor for phosphate release and metal bioprecipitation) gave sustained removal of both metals in a flow through bioreactor, with more extensively accumulated Ni. We propose 'Microbially Enhanced Chemisorption of Heavy Metals' (MECHM) to describe this hybrid mechanism of metal bioaccumulation via intercalation into preformed, biogenic crystals, and note also that MECHM can promote the removal of the transuranic radionuclide neptunium, which is difficult to achieve by conventional methods.

Biomass↗

Changes in intragastric meal distribution are better predictors of gastric emptying rate in conscious pigs than are meal viscosity or dietary fibre concentration.

The effect of dietary fibre on the gastric emptying rate of solids is controversial. Similarly, the mechanisms by which it modulates food intake are partially unknown. Gastric emptying and proximal v. distal stomach filling were evaluated in triplicate on four conscious pigs using scintigraphic imaging. Each animal received in an isoenergetic manner a concentrate low-fibre diet enriched in starch (S) and two high-fibre diets based on sugar beet pulp (BP) or wheat bran (WB). All meals had the same viscosity before ingestion (100.0-100.5 Pa.s). Viscosity of the gastric contents was measured in four additional animals fitted with a gastric cannula. The gastric emptying rate of BP diet was significantly slower than S and WB diets (t1/2 78.4 (sem 5.68), 62.8 (sem 10.01) and 111.6 (sem 10.82) min for S, WB and BP diets respectively, P<0.05). For BP diet only, rate of distal stomach filling was steady during the first 120 min after the meal whereas that of S and WB diets decreased in an exponential manner. Numerous backflow episodes from the distal into the proximal stomach were observed for BP diet that generated the larger intragastric viscosity (0.26 (sem 0.03), 0.3 (sem 0.02) and 0.52 (sem 0.002) Pa.s for S, WB and BP respectively). In conclusion, viscosity of the meal or the percentage total fibre, unlike viscosity of the gastric contents, are poor predictors for emptying. The reduced emptying rate observed with BP is associated with major changes in intragastric distribution of the meal absent with WB and S diets.

Animal Feed↗

111In-oxine labelling of tumour-cytotoxic macrophages generated in vitro from circulating blood monocytes: an in vitro evaluation.

The labelling of ex-vivo activated macrophages with doses of 111In-oxine sufficient for gamma camera imaging does not damage cell viability or the functional competence of cells (secretion of tumour necrosis factor-alpha and interleukin-6). The mean labelling efficiency was about 84%. Release of 111In equivalent to 15% occurred over 24 h under cell culture conditions, indicating good stability of the radioactive cell label. 111In-oxine-labelled macrophages are a suitable tool for biokinetic studies of adoptive immunotherapy.

Cell Survival↗

Use of functional maps in renal scintigraphy to detect segmental arterial lesions.

Renography using a gamma camera, a minicomputer, [123I]orthoiodohippurate ([123I]OIH), and a canine model was employed to evaluate computer-generated maps of regional renal function. Renograms were obtained before and after ligations of the right renal arterial branch in four dogs, with subsequent angiographic and histologic confirmation of the lesions. Postoperative time-activity curves were normal. Washout and persistence index in three of four right kidneys showed regional abnormality. Functional renal mapping may provide a clinical technique for evaluating human renal vascular hypertension.

Animals↗