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The search for tumor-associated proteins in pleural effusions by means of monoclonal antibodies and a dot blot assay.

Liquid moiety of 61 pleural effusions was tested for tumor-associated proteins (TAP) by means of a dot immunobinding (dot blot) assay (DIA) and a panel of monoclonal antibodies (Moabs). The sensitivity of the assay was checked using a purified, serially diluted carcinoembryonic antigen (CEA) preparation and an anti-CEA monoclonal IgG system. The latter was examined using both DIA and enzyme-linked immunosorbent assay ELISA solid phase assays in simulated conditions that mimicked the protein content of effusions. Finally, the results of DIA were compared to the immunohistochemistry carried out on cell sediments from the same effusions with similar Moabs. It was found that the prevalence of several TAPs, including CEA, epithelial membrane antigen (EMA), vimentin, tenascin, and Thomsen Friedenreich antigen, was significantly higher in the malignant effusions than in the nonmalignant ones. A total, larger than 2, of detected TAPs in a given fluid, was found almost exclusively in malignant effusions (p less than 0.0001). The detection limit of the DIA for a CEA was determined at 5 ng/ml, while for the ELISA it was 1 ng/ml. Several TAPs, especially the CEA, could be detected in parallel tests, carried out on the liquid moiety and the cell sediments of malignant effusions. The evaluation of selected TAPs in pleural effusions by dot blot assay may be of clinical value.

Antibodies, Monoclonal↗

Patterns of troponin T expression in mammalian fast, slow and promiscuous muscle fibres.

The distribution of troponin T (TnT) species in typed single muscle fibres was analysed using one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) and a monoclonal antibody specific for fast TnT. Fibres taken from erector spinae (Es), plantaris (Plt), diaphragm (Dia) and soleus (Sol) muscles of adult rabbits were pretyped as fast-twitch-glycolytic (FG), fast-twitch-oxidative-glycolytic (FOG), slow-twitch-oxidative (SO) or promiscuous (P) using a combination of histochemical staining and PAGE. Although none of the four size classes of TnT was either muscle or fibre type specific, their pattern of expression differed in each muscle and between the fibre types. FG fibres expressed TnT1f or TnT2f as predominant species, depending on the muscle; TnT3f and TnT4f were minor components. In contrast, all size classes of TnT were expressed in varying proportions in FOG fibres from Es and Plt, while those from Dia resembled FG fibres, expressing TnT1f as their major species. P fibres from Es, Plt, and Sol exhibited a distinctive pattern of fast TnT expression, TnT3f being the predominant species. Dia differed from the other muscles as TnT1f was the dominant fast TnT species in its P fibres as it is in the Dia fast fibres. Quantitative analysis of one- and two-dimensional gels revealed that the P fibres could be divided into two classes, those that exhibited discoordinate expression of fast and slow TnTs, myosin light chains and myosin heavy chains and those in which their expression was coordinate. In addition low levels of TnT4f were detected in SO fibres and of slow TnT in fast fibres.

Animals↗

MRI location of the distal dural ring plane: anatomoradiological study and application to paraclinoid carotid artery aneurysms.

The distal dural ring plane (DDRP) separates the intradural from the extradural paraclinoid internal carotid artery. The purpose of this study was to evaluate its position with MR imaging. The protocol used a T2-weighted sequence in two orthogonal planes: diaphragmatic (DIA-P) and carotid (CAR-P). The DDRP passes through four anatomoradiological reference points (RefP). We developed on a cadaveric model a correlation method supported by correlation lines and angles (CA) projecting the RefP toward the DDRP. RefP were correlated to the DDRP in 65-84% of cases in the DIA-P and 60-76% of cases in the CAR-P. CA were identified and correlated to the DDRP, respectively, in 87% and 60% of cases in the DIA-P, and 60% and 51% of cases in the CAR-P (failure often related to a lack of visibility of just one RefP). A higher tissular contrast in living subjects allowed the identification of CA in 90% and 80% of cases, respectively, in the DIA-P and the CAR-P. We propose that CA, when identified, should be considered as an approximation of the inferior radiological limit of the DDRP curve. In difficult angiographical cases, this MRI protocol could help to locate paraclinoid aneurysms on both sides of the cavernous sinus roof.

Adult↗

Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells.

Many pluripotent embryonal carcinoma (EC) cell lines and all embryonic stem (ES) cell lines have hitherto been maintained in the undifferentiated state only by culture on feeder layers of mitomycin C-treated embryonic fibroblasts. We now demonstrate that medium conditioned by incubation with Buffalo rat liver (BRL) cells prevents the spontaneous differentiation of such cells which occurs when they are plated in the absence of feeders. This effect is not mediated via cell selection but represents a fully reversible inhibitory action ascribed to a differentiation-inhibiting activity (DIA). BRL-conditioned medium can therefore replace feeders in the propagation of homogeneous stem cell populations. Such medium also restricts differentiation in embryoid bodies formed via aggregation of EC cells and partially inhibits retinoic acid-induced differentiation. The PSA4 EC line gives rise only to extraembryonic endoderm-like cells when aggregated or exposed to retinoic acid in BRL-conditioned medium. This suggests that DIA may be lineage-specific. DIA is a dialysable, acid-stable entity of apparent molecular weight 20,000-35,000. Its actions are reproduced neither by insulin-like growth factor-II nor by transforming growth factor-beta. DIA thus appears to be a novel factor exerting a negative control over embryonic stem cell differentiation.

Animals↗

Antigen detection immunoassay using dipsticks and colloidal dyes.

A dipstick colloidal dye immunoassay (DIA) for multiple antigen detection is described. The test combines the concepts of double antibody (Ab) sandwich ELISA, dot blotting, and colloidal particle-linked Abs to produce a dipstick test for multiple antigen (Ag) detection. Dipsticks prepared from Ab coated nitrocellulose membrane mounted on acetate strips served as the assay capture matrix. Abs absorbed to colored dye particles from a family of commercially available textile dyes (Dye/Ab reagent) served as Ag detecting reagents. DIA and enzyme labelled dot blot assays showed similar Ag detection limits down to a sensitivity of 10 ng/ml. In a pilot study, an assay designed to detect species-specific IgG for use in mosquito bloodmeal identification demonstrated the feasibility of the technique. Experiments comparing bloodmeal analysis of mosquitoes using DIA and ELISA methods showed 100% agreement. This DIA method provides an inexpensive, simple, robust test for multiple Ag detection without instrumentation suitable for a wide variety of field applications.

Aedes↗

Dot immunobinding assay as a new diagnostic test for human hydatid disease.

Bovine and human hydatid antigens collected from hepatic cysts and characterized by SDS-PAGE immunoblotting show similar patterns. The bovine hydatid antigen has been used to develop a simple and fast in vitro diagnostic assay for human hydatidosis. This method, named HA-DIA (hydatid antigen dot immunobinding assay), consists of incubation of a serum sample with a textile colloidal dye (pink) and a nitrocellulose stick to which the hydatid antigen has been bound. The presence of parasite-specific antibodies leads to dyeing of the stick reactive area, and a coloured spot appears. HA-DIA sensitivity and specificity have been studied in comparison with RAST-IgE and ELISA-IgG by testing 17 sera of patients with hydatid disease and 36 control sera from patients affected with other parasitic and non-parasitic diseases. HA-DIA showed positive results in all the patients' sera and in none of the control sera. Correlation with ELISA--IgG and RAST-IgE was significant. HA-DIA has been demonstrated to be of good predictive value, allowing a speedy diagnosis of hydatid disease. In view of its simplicity, not requiring any laboratory instruments, it is particularly suitable for large-scale field screening.

Animals↗

Comparison of the dot-immunobinding assay with the complement fixation test for the detection of Brucella antibodies in sheep.

A dot-immunobinding assay (DIA), using as antigen a sonic extract of Brucella abortus dotted on nitrocellulose bound to a plastic strip, was employed for the detection of Brucella antibodies in 666 sheep sera. The results were compared with the complement fixation test (CFT). All the 242 sera belonging to two flocks were found to be negative by DIA. CFT was negative in 239 cases, whereas three samples showed anti-complementary activity. Of the 424 sera from the remaining three flocks, 98 were positive by both tests and six were positive in DIA, but negative in CFT. In addition, 14 of the 19 anti-complementary sera were also positive by DIA.

Animals↗

Dot immunobinding assay for the detection of bluetongue virus antibodies in sheep experimentally inoculated with bluetongue virus type 1.

Dot immunobinding assay (DIA) was evaluated for the detection of bluetongue virus (BTV) antibodies in sheep experimentally inoculated with BTV 1. Serum samples collected on 14, 21, 28, 43 and 60 day post infection (dpi) were positive for precipitating antibodies by the agar gel precipitation test (AGPT) while antibodies could be detected as early as 7 dpi by DIA and ELISA. Virus neutralizing antibodies were detected first at 14 dpi. The sensitivity of the four tests was compared on the same serum samples collected at different intervals. The results indicated that DIA was more sensitive than AGPT and the serum neutralization test and as sensitive as ELISA. Thus due to sensitivity simplicity and economy, DIA could replace AGPT for diagnosis and serological survey for BTV infection in animals.

Animals↗

The ultrastructure of the prothoracic gland/corpus allatum/corpus cardiacum ring complex of the Australian sheep blowfly larva Lucilia cuprina (Wied.) (Insecta: Diptera).

The ultrastructure of the constituent endocrine glands within the ring complex of Lucilia cuprina larvae has not been previously described. This study investigated the ring complex of mid-third instar larvae. Three distinct endocrine cell types were identified: (1) prothoracic gland (PTG) cells which constituted the major cell type; (2) corpus allatum (CA) cells, localized in the anterior central region, and (3) corpus cardiacum (CC) cells, located posteriorly, ventral to the aorta. PTG cells were identifiable by their large ovoid nuclei (9-14 microns dia, length 12-18 microns) and numerous cytoplasmic lipid vacuoles. The plasma membrane of peripheral PTG cells were invaginated to form intercellular channels. The CA cells are characterized by ovoid nuclei (6-7.5 microns dia, 6.5-9 microns length) and electron dense staining cytoplasm. Compared to PTG cells the CA cells had smaller nuclei and lower nucleus:cytoplasm cell ratio. Extensive networks of highly irregular, electron-lucent intracellular spaces, dispersed throughout the cytoplasm were also characteristic of CA cells at this developmental stage. These spaces often contained membrane bound lipid vacuoles occurring singly or as aggregates. The CC contained both intrinsic and extrinsic neural components. The intrinsic cells were characterized by circular nuclei (6.5-8.5 microns dia), prominent nucleolus and numerous cytoplasmic electron-dense neurosecretory granules (100-240 nm dia). The extrinsic axons and terminals within the CC contained electron-dense neurosecretory granules (80-150 nm), neurotubules and mitochondria.

Animals↗

Improved fecal DNA test for colorectal cancer screening.

BACKGROUND & AIMS: Fecal DNA testing has shown greater sensitivity than guaiac-based occult blood tests for noninvasive colorectal cancer (CRC) screening. The prototype assay (version 1), which analyzed 22 gene mutations and DNA integrity assay (DIA), showed a sensitivity of 52% for CRC detection and a specificity of 94% in average-risk individuals. The present study was conducted to determine the sensitivity and specificity of a second-generation assay (version 2) that uses improved DNA stabilization/isolation techniques and a new promoter methylation marker. METHODS: Forty patients with CRC and 122 subjects with normal colonoscopy provided stool samples to which DNA preservation buffer was added immediately. DNA was purified using gel-based capture, and analyzed for the original panel of 22 mutations, DIA, and 2 new promoter methylation markers. RESULTS: By using DNA that was optimally preserved and purified from stool, the sensitivity of the prototype version 1 assay increased to 72.5% because of enhanced performance of DIA. Vimentin gene methylation alone provided sensitivity and specificity of 72.5% and 86.9%, respectively. The optimal combination of vimentin methylation plus DIA resulted in 87.5% sensitivity and 82% specificity; cancers were detected regardless of stage or location. False-positive vimentin methylation was associated with older age. CONCLUSIONS: An improved fecal DNA test that incorporates only 2 markers shows much higher sensitivity for CRC. The new assay is easier to perform and should be less costly, thereby facilitating its use for noninvasive CRC screening.

Age Factors↗

Effect of heart failure on skeletal muscle myofibrillar protein content, isoform expression and calcium sensitivity.

BACKGROUND: Alterations in skeletal muscle with heart failure contribute to exercise intolerance and physical disability. The majority of studies to date have examined abnormalities in skeletal muscle oxidative capacity and mitochondrial function. In contrast, less information is available regarding the effect of heart failure on myofibrillar protein metabolism and function. To address this issue, we examined the effect of heart failure on skeletal muscle myofibrillar protein content, isoform distribution and Ca2+ sensitivity. METHODS: We measured skeletal muscle myosin heavy chain (MHC) and actin protein content and MHC isoform distribution in soleus (SOL), extensor digitorum longus (EDL), plantaris (PL) and diaphragm (DIA) muscles and myofibrillar Ca2+ sensitivity in EDL muscles from Dahl salt-sensitive rats with (high-salt fed: HS; n=10) or without heart failure (low-salt fed: LS; n=8) and assessed the relationship of these variables to markers of disease severity. RESULTS: No differences in muscle mass were found. Similarly, no differences in MHC (mean+/-SE; SOL: 1353+/-29 vs. 1247+/-52; EDL: 1471+/-31 vs. 1441+/-31; PL: 1207+/-66 vs. 1286+/-36; DIA: 1166+/-42 vs. 1239+/-26 AU/microg protein) or actin (EDL: 348+/-13 vs. 358+/-19; PL: 245+/-20 vs. 242+/-9; DIA: 383+/-9 vs. 376+/-17 AU/microg protein) protein content or the actin-to-MHC ratio were observed, with the exception of lower (P<0.01) actin content in the soleus of LS rats (352+/-7 vs. 310+/-8 AU/microg protein). MHC isoform expression (I, IIa, IIx, IIb) did not differ between groups in SOL (I: 89+/-1% vs. 85+/-2%; IIa: 11+/-1% vs. 15+/-2%), EDL (IIx: 43+/-10% vs. 38+/-10%; IIb: 57+/-10% vs. 62+/-10%), PL (I: 6+/-4% vs. 3+/-3%; IIa: 1+/-1% vs. 1+/-1%; IIx: 31+/-3% vs. 26+/-4%; IIb: 62+/-5% vs. 71+/-6%) or DIA (I: 43+/-6% vs. 36+/-6 %; IIa: 9+/-1% vs. 7+/-1%; IIx: 47+/-6% vs. 56+/-7%; IIb: 2+/-1% vs. 1+/-0.5%) muscles. Moreover, heart failure did not affect the Ca2+ sensitivity (i.e., pCa50) of extensor digitorum longus myofilaments (5.68+/-0.11 vs. 5.65+/-0.09). Finally, MHC and actin content, MHC isoform distribution and myofibrillar Ca2+ sensitivity were not related to markers of disease severity. CONCLUSIONS: Our results show that this animal model of heart failure is not characterized by alterations in the quantity or isoform distribution of key skeletal muscle myofibrillar proteins or the Ca2+ sensitivity of isometric force production. These findings suggest that alterations in skeletal muscle myofibrillar protein metabolism do not develop in parallel with myocardial failure in the Dahl salt-sensitive rat.

Actins↗

Conventional assessment of needle biopsy specimens is more useful than digital image analysis of proliferation and DNA ploidy in prediction of positive surgical margins at radical prostatectomy.

OBJECTIVES: The preoperative prediction of the likelihood of positive surgical margins (+SMs) at radical retropubic prostatectomy (RRP) may be useful for counseling and determining the surgical approach. The aim of this study was to assess the additional value of digital image analysis (DIA) of ploidy and proliferation on needle biopsies, in addition to the known preoperative predictors of +SMs at RRP. METHODS: We identified 454 patients treated by RRP at our institution from 1995 to 1998 for prostate cancer verified by transrectal ultrasound-guided biopsy, with a specimen adequate for DIA. Patients receiving preoperative hormonal therapy were excluded. The clinical features, transrectal ultrasound-guided biopsy findings, and DIA evaluation of MIB-I immunostaining and DNA ploidy were assessed in a multivariate logistic regression model to predict for +SMs at RRP. RESULTS: The mean +/- SD age at treatment was 64.5 +/- 6.5 years, the percentage of positive cores was 40.4% +/- 24.3%, the median prostate-specific antigen level was 6.3 ng/mL (range 0.6 to 112.0), median biopsy Gleason score was 6 (range 4 to 9), and median percentage of diploid nuclei was 67% (range 0% to 100%). Of the 454 patients, 185 (40.7%) had +SMs; this finding was time dependent (1995 to 1996, 45% and 1997 to 1998, 31%; P = 0.004). Univariately, preoperative prostate-specific antigen, biopsy Gleason score, extent of cancer on biopsy, MIB-1 expression, percentage of diploid or nondiploid nuclei, and year of surgery were predictive for +SMs. On multivariate analysis, the preoperative prostate-specific antigen level, biopsy Gleason score, percentage of positive cores, and year of surgery remained significant. CONCLUSIONS: The results of our study have shown that the likelihood of +SMs at RRP is best predicted on the basis of conventional prognostic factors. The DIA features of needle biopsies did not provide additional predictive power.

Adult↗

Determination of interfering triazine degradation products by gas chromatography-ion trap mass spectrometry.

Deethylatrazine (DEA), an atrazine degradation product, has been added to the US Environmental Protection Agency's Drinking Water Contaminant Candidate List (CCL). In its gas chromatographic analysis, DEA can coelute with deisopropylatrazine (DIA), another degradation product. The present work demonstrates that the coelution of DEA and DIA can induce a significant (up to approximately 50%) positive bias in the DEA determination, when using an ion-trap mass spectrometer as the detector. The DIA determination is unaffected by the coelution within experimental error. This may be explained in terms of gas-phase ion fragment populations. A correction factor to the observed DEA concentration may be developed based on the measured DIA concentration.

Atrazine↗

Microbial origin of glutamate, hibernation and tissue trauma: an in vivo microdialysis study.

Using quantitative microdialysis in hibernating Arctic ground squirrels (AGS), striatal glutamate concentrations ([glu](dia)) progressively increased to approximately 200 microM after 3 days of microdialysis in euthermic but not hibernating ground squirrels. Initially, the progressive increase in [glu](dia) was thought to be related to greater tissue response in euthermic animals. Alternatively, given the vastly different body temperatures between the two groups (37 vs. 3 degrees C), glutamate might have originated from microbes, replicating at a faster rate in the warmer animals. To test these hypotheses, microdialysis was repeated using sterile technique and tissue response surrounding the probe tract was assessed in hematoxylin and eosin stained sections. Using sterile microdialysis technique, traumatic tissue response was greater in euthermic compared to hibernating tissue. However, sterile microdialysis abolished the progressive increase in glutamate. To confirm the microbial origin of glutamate we monitored [glu](dia) collected in vitro from probes immersed in glutamine-rich liquid medium incubated at 37 degrees C. In vitro, [glu](dia) increased as much as in vivo. Two bacteria isolated from in vitro dialysate and liquid medium were both identified as Ralstonia pickettii. Growth of these isolates as well as glutamate release was enhanced when glutamine rather than NH(4)NO(3) was added to the medium suggesting the bacteria utilize glutamine preferentially over ammonium as a nitrogen source.

Animals↗

sICAM-1 correlates with myocardial ICAM-1 expression in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is etiopathogenically linked to intramyocardial inflammation, which is reflected by ICAM-1 abundance. We investigated whether soluble ICAM-1 (sICAM-1) levels in the sera of DCM patients are associated with intramyocardial ICAM-1 expression. METHODS: Immunohistochemically detected ICAM-1 expression was quantified semiquantitatively in endomyocardial biopsies from DCM patients (n=45; n=17 females; age: 48+/-15 years) and from n=12 donor hearts (controls) by a human observer (baseline vs. enhanced expression) and quantitatively by a digital image analysis (DIA) system. The DIA-measured qualities were area fraction (AF), surface-volume ratio (SVR) and integral optical density (ID). The sICAM-1 levels of the DCM patients and n=12 healthy volunteers (controls) were measured by ELISA (means of duplicate measurements). Intramyocardial ICAM-1 expression and sICAM-1 levels were compared in these DCM patients. RESULTS: Of the DCM patients, n=24 (53%) demonstrated statistically higher sICAM-1 levels compared to controls (>198 ng/ml). By semiquantitative and quantitative DIA evaluation, endothelial ICAM-1 abundance was present in n=25 (56%) of the DCM biopsies. sICAM-1 correlated significantly (P<0.001) both with the semiquantitatively assessed and the DIA-measured ICAM-1-AF, the ICAM-1-SVR and the ICAM-1-ID. The positive predictive value of sICAM-1 measurements for intramyocardial ICAM-1 abundance was 96%, and the negative predictive value was 71%, with a receiver operating characteristic area under the curve of 0.93. Furthermore, sICAM-1 levels correlated with intramyocardial T-lymphocytic (CD2+/CD3+) infiltrates (P<0.03). CONCLUSIONS: Measurement of non-invasively obtained sICAM-1 reliably reflects intramyocardial ICAM-1 expression and may therefore serve as a non-invasive marker of inflammatory activity in DCM.

Adult↗

Peptide detection in single cells using a dot immunoblot assay.

A highly sensitive dot immunoblot assay (DIA) for the detection and quantitative measurement of small peptides in single cells is presented. This DIA protocol is simple, rapid, and produces no radioactive waste. Its femtomole sensitivity is 100 fold greater than previously described DIAs. This DIA method is sufficiently sensitive to allow reliable peptide measurements to be obtained from a single cell in a manner than is faster and easier than other peptide detection procedures. This method can also be used for several other purposes, including assessing antibody specificity and peptide quantification.

Analysis of Variance↗

Prognostic factors of hematological recovery in life-threatening nonchemotherapy drug-induced agranulocytosis. A study of 91 patients from a single center.

OBJECTIVES: We studied clinical factors that may influence the duration of hematological recovery to reach neutrophil counts and thus, indirectly, the prognosis in patients with life-threatening drug-induced agranulocytosis (DIA). METHODS: Using univariate and multivariate analyses with Cox's proportional hazard models, we determined the prognostic factors for hematological recovery, defined as neutrophil counts>0.5 and>1.5.10(9)/L, in 91 patients with established life-threatening DIA. RESULTS: Multivariable analysis showed that neutrophil count<0.1.10(9)/L (at diagnosis) and infection profile: severe infections or septic shock, adversely influenced the neutrophil recovery (for the two neutrophil levels). Hematopoietic growth factors were significantly associated with rapid hematological recovery (for the two neutrophil levels). Documented microbial infections and antiplatelet DIA were also associated with rapid hematological recovery (for a neutrophil count>1.5.10(9)/L). CONCLUSION: Our findings demonstrate that in life-threatening DIA, hematological recovery is mainly dependent of the neutrophil level, the type of infections and the utilization of hematopoietic growth factors.

Acute Disease↗

A novel 99mTc delivery system using (n,gamma)99Mo adsorbed on a large alumina column in tandem with Dowex-1 and AgCl columns.

99Mo of specific activity 7.4-14.8GBq (200-400mCi)/g was adsorbed on a 'jumbo' alumina column (40g, 90mm(H) x 20mm (dia.); 50g, 65mm(H) x 35mm(dia.). [99mTc]TcO4-, eluted with 50-70ml normal saline and applied to a tiny column of a strong anion exchanger, Dowex-1 x 8, 10-15 mg, 8-12 mm(H) x 1 mm(dia.). Pertechnetate was eluted from the Dowex-1 column with 5-6 ml of 0.2M Nal followed by washing with 1.5-1.8 ml water. Iodide was removed from this eluate by passage through a 1 g AgCl column (12 mm (H) x 8 mm (dia.)). The final product, pertechnetate, was recovered in 6.5-7.8 ml, while the NaCl content was close to that of normal saline. Each elution operation was complete in approximately 45 min. The mean practical yield was approximately 86% (n = 5). Closed cycle operation with sterile connecting tubes and multi-way stop-cocks was practised. The quality of the [99mTc]NaTcO4 thus obtained complies with the specifications applicable for radiopharmaceutical use. The major merit over other post-elution concentration methods is that the new procedure can function nearly independently of the volume of the primary eluate (in normal saline) from the alumina column generator (ACG). 99mTc generators containing as much as 80-100 g alumina for holding 14.8-18.5GBq (400-500 mCi) 99Mo (at the reference time) are feasible using approximately 15 mg Dowex-1 bed mass. A relatively user-friendly--cum--producer-friendly 99mTc generator system has been demonstrated making use of the inexpensive and easy to prepare (n,gamma)99Mo. The method is also applicable for the more costly 188W-188Re generator.

Journal Article↗