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Development of a three-dimensional data acquisition method for standardization of beta-emitting nuclides

We have developed a three-dimensional data-acquisition system with which pulse heights from an array of detectors can be multi-scaled with dwell times as short as 31 ns. The main part of the system consists of three ADCs of SAR (Successive Approximation Register) type, a 32 MHz oscillation clock and DRAM (Dynamic Random Access Memory) of 192 Mbyte capacity. The clock time is determined by count the clock pulse generated by 28 bits synchronous counter. Both the pulse height and the time information are stored at an array of DRAM, of 40-bits width, 12-bits for pulse height and 28-bits for clock time. The technique is particularly suitable for experiments such as both double and triple coincidence distributions are required. Virtues of the method are demonstrated by measuring the activity of 14C with a 3-PM liquid scintillation counting system. The computer discrimination together with the MCTS (multi-channel time scaling) technique is applied for efficiency variation method in the analysis.

Journal Article↗

Feasibility of radioimmunoguided surgery of colorectal carcinoma using indium 111 CEA specific antibody and simulation with a phantom using 2 steps targetting with bispecific antibody.

The study was undertaken to define the potential use of radiolabelled (Indium 111 or Technetium 99 m) carcinoembryonic antigen specific antibody (CEA f(ab')2) for the radioimmunodetection of colorectal cancer using an intraoperative hand-held gamma probe. A clinical study performed with ten patients showed that tumor with good uptake of CEA specific antibody could be detected with sufficient contrast only in two patients. Results of a biodistribution study performed with tumor fragment and normal tissue countings in a gamma counter showed high tumor uptake in five patients. There was no correlation between tumor uptake and the count rates measured intraoperatively. To increase the signal/background of the gamma probe, a simulation study with a peritoneal cavity phantom was performed. We determined the efficiency of a two steps targetting method compared to the direct method. We simulated different tumor sizes with plexiglas balls (0.5, 1, 2, 5 ml) and tested two scintillators (NaI, BgO). Experiments were performed with 111 In and 99 m Tc. The two steps targetting method was better than direct method. The results of simulation with direct method radiolabelled with 111 in confirmed our clinical study: no efficiency of a gamma probe for the surgeon to detect a tumor. However the two steps targetting method (indirect labelling method) was very encouraging to detect tumors (size 1 and 2 ml) and definitively convincing with 99 m Tc.

Antibody Specificity↗

Performances of a new prototype handheld scintillating probe for the search of sentinel lymph nodes in breast cancer.

AIM: The aim of this study is to evaluate the performances of a new prototype handheld gamma probe in a series of patients with infiltrative breast cancer justifying sentinel lymph node (SLN) excision. METHODS AND PATIENTS: SLN excision was performed on nine patients being treated for infiltrative breast cancer. After preoperative radio-isotope injection and lymphoscintigraphy, individual removal of all radioactive nodes was performed after their localisation using a novel new prototype handheld gamma intraoperative probe named CarolIReS. The activity of SLN following resection has been measured by a gamma ray counter. The mean geometrical detection efficiency of this gamma ray counter has been obtained by Monte Carlo simulation. RESULTS: With respect to the total number of SLNs identified by the CarolIReS probe, the detection probability was 80% for the lymphoscintigraphy. A mean number of 2.2 (1-5) SLNs per patient was detected after the complete SLN procedure. Among the removed SLNs, 19 were axillary SLN, 17 were located in the level I of Berg, two were located in the Rotter area and one was an intramammary SLN (ISLN) located in the lower inner area of the breast. The detection efficiency of the CarolIReS probe ranged from 2.1 to 100.0cpskBq(-1) referred to the activity of the SLN at the time of the surgery. CONCLUSION: This study shows that the CarolIReS probe is well adapted to the SLN detection and allows an efficient identification of both axillary and intramammary lymph nodes.

Adult↗

Measurement of gastric emptying by intragastric gamma scintigraphy.

Gastric emptying is usually measured in animals and humans by dilution/sampling or external scintigraphy. These methods are either time consuming or require expensive equipment. The capacity of a miniature gamma counter positioned in the stomach to measure emptying of liquid and solid meals was evaluated. In eight conscious pigs fitted with gastric and duodenal cannulae, gastric emptying of saline (500 mL), dextrose (20%, 500 mL), porridge (300 g) and scrambled eggs (300 g), all labelled with 3.5 MBq 99mTC, was evaluated. When positioned in the antrum the probe was unable to quantify gastric emptying. In contrast, measurements of the fractional emptying of saline over 4-min periods by the probe positioned in the corpus and quantification of radioactivity in the duodenal effluent correlated closely (r = 0.88, P < 0.05). Gastric emptying (50% emptying time) of saline and both solid meals measured by the probe was not significantly different from quantification of the duodenal effluent volume. No difference was observed also for the dextrose meal but only while gastric acid secretion was suppressed by omeprazole. We conclude that an intragastric gamma counter permits measurement of gastric emptying of homogeneous meals provided meal stimulation of gastric secretion was not extensive. This was possible probably by monitoring emptying from the proximal stomach.

Animals↗

Measurement techniques for radium and the actinides in man at the Center for Human Radiobiology.

Various techniques are employed to determine the amounts, retention, and distribution of radioactivity in human subjects in vivo. The principal method is gamma-ray spectrometry with large NaI(Tl) scintillation crystals ("whole-body counting"). The geometries used include an arc of 1.5-m radius in which all parts of the body are roughly equidistant from the detector, a reclining chair and a flat bed with detectors placed above and below the subject. When a sufficient amount of radioactivity is present in a subject, scanning techniques assist in determining its distribution in the body. Specialized instruments such as a xenon-filled proportional counter and a dual-crystal (phoswich) detector are used to measure low-energy photon emitters, primarily plutonium and americium. americium. There are three primary methods of calibrating the detectors. The first is analytical, in which a rigorous mathematical treatment is employed; the second involves the administration of tracer amounts of radioactivity to human volunteers; the third consists of determining detector response to known amounts of radioactivity in a phantom. All three methods can be intercompared, and further evaluated by comparing the results of measurements in vivo with those of postmortem analyses. For both radium and thorium cases measured in vivo, the interpretation of the results is complicated by the fact that neither radium nor thorium emit gamma rays of any consequence. Instead, the observed gamma rays result from the decay of 214Bi (RaC) and 208Tl (ThC"), respectively. Since each of these nuclides is preceded in the decay chain by an isotope of the noble gas radon, some of which is exhaled, its activity is not equal to that of the parent radium or thorium. Therefore, breath samples are collected to determine the exhalation rate of the precursor isotope, 222Rn (radon) or 220Rn (thoron). The total body content is then the sum of the gamma activity and the exhaled radioactivity, referred to as the retained and emanating fractions, respectively.

Actinoid Series Elements↗

[Solubilization of biological tissues for measuring radioactivity in a pharmacological experiment].

For studying distribution of drugs and their metabolites in organs of experimental animals by the method of radioactive indicators with recording of measurements of the compounds under study by means of a liquid-scintillaton counter, there is described a simple and available method of complete solubilization of a biological tissue. The method makes it possible to dissolve up to 10 g of a biological tissue without preliminary lyophilization.

Animals↗

Calibration of a radioactive ink-based stack phantom and its applications in nuclear medicine.

This paper describes a stack phantom useful for imaging complex activity distributions. It is based on images printed with radioactive ink using a commercial ink-jet printer. The application for the phantom is in the evaluation of planar and SPECT scintillation camera images and for validation of Monte Carlo simulated images. The accuracy in generating the activity distributions on paper sheets is especially important. Here we describe the calibration procedure for the ink-jet printer. The goal of the printer calibration is to find the relationship between the digital image count (voxel grey level) and its corresponding activity on the paper sheets (radioactivity). The relationship between the voxel grey level and the radioactivity on the paper sheets (measured by scanning technique and well counter) was found to be logarithmic, and a 3rd degree polynomial was found to fit the relationship. The distribution of radioactivity in the ink cartridge was investigated by pinhole SPECT. The distribution of (99m)Tc solution was found to be homogeneous in the ink solution. Experimental studies were done directly on Monte Carlo simulated heart images from the NCAT phantom. The result showed that the simulated images are similar to the images measured using the ink-jet technique. This stack phantom could be a promising solution with an advantage that the exact geometry generated in Monte Carlo could be imitated in the phantom. The phantom is a very flexible device and clearly much more versatile than conventional phantoms which have a fixed geometry and spatial limitation.

Calibration↗

Measurements of single event spectra with a wall-less proportional counter in low LET radiation fields.

Measurements have been made on 60Co gamma rays from a point source and on 6 MV roentgen rays from a linear accelerator with a wall-less proportional counter. Single event spectra have been measured in sites of 0.5-2 mum in diameters stimulated with a tissue equivalent gas. Calculations of the relative variance in LET are performed and compared with the relative variance of the measured distributions for estimates about the straggling contribution.

Cobalt Radioisotopes↗

Reconstruction of cluster distributions at 100% detection efficiency for a track-nanodosimetric counter through a Bayesian analysis.

A Bayesian unfolding has been applied to ionisation distributions due to 5.4 MeV alpha particles in a 20-nm site obtained using Monte Carlo simulations, taking into account different detection efficiency conditions. The ideal case of a target volume with uniform efficiency has been investigated to study the dependence of the reconstruction on prior distributions. A simplified approach has been used to treat the case of a target volume with non-uniformly distributed efficiency, like the sensitive volume of the track-nanodosimetric counter. Our results point out that Bayesian analysis provides a effective tool for reconstructing the true ionisation distributions, well beyond the maximum measured cluster size.

Algorithms↗

Validation of a multiwell gamma-counter for measuring high-pressure liquid chromatography metabolite profiles.

OBJECTIVES: The purpose of this study was to verify the accuracy and reproducibility of a multiwell counter to assess its suitability for use within human PET studies in which metabolizing (11)C tracers are used. Such tracers often require metabolite analysis for deriving plasma metabolite-corrected input curves. High-pressure liquid chromatography (HPLC) with on-line activity measurement is often unreliable for later plasma samples due to the poor sensitivity of the on-line activity detector. Fraction collector obtained HPLC samples that are counted in a separate high-sensitivity well counter can be an alternative to overcome poor counting statistics. METHODS: Several experiments to evaluate background counting, reproducibility, and linearity were performed to validate the accuracy, precision, and detection limits of the well counter. In addition, measurements on a series of samples resembling activity profiles as seen within human (11)C-flumazenil studies were performed to evaluate the performance of the well counter for clinically relevant data. RESULTS: The tests proved that the well counter detection limit, linearity, and reproducibility were more than sufficient in circumstances as seen during patient studies for samples with both high and low activity. CONCLUSION: The use of a multiwell counter is a good alternative for the on-line activity detector of the HPLC, allowing derivation of plasma metabolite fractions with high accuracy and reproducibility.

Carbon Radioisotopes↗

Radioisotope-guided surgery in patients with neuroendocrine tumours.

We evaluated a hand-held scintillation detector for intra-operative localisation of somatostatin-receptor-positive tumours in situ, and after excision, as an addition to preoperative scintigraphy with [111In-DTPA-Phe1]octreotide. Using the hand-held detector, the suspect tumour/normal tissue ratio R(in situ) between measurements was calculated for 23 patients with neuroendocrine tumours. The count rates of excised tumour and normal tissue were also measured ex vivo and their ratio R(ex vivo) was calculated. In midgut carcinoid (MC) patients (all scintigraphy positive), 4/29 macroscopically identified tumours gave false R(in situ). Tumour/blood 111In activity (T/B) ratios measured in a gamma counter were all high (27-650). In patients with medullary thyroid carcinoma (8/10 scintigraphy positive), misleading R(in situ) were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in MC patients. 2/4 patients with endocrine pancreatic tumours (EPTs) had positive scintigraphy, reliable intra-operative measurements, and very high T/B ratios (910-1,500). 1 patient with a gastric carcinoid had correct R(in situ) and R(ex vivo), with high T/B ratios (71-210). 1 patient with sporadic insulinoma had negative scintigraphy and 1 patient with neuroendocrine carcinoma of the uterus also had low T/B ratios. In most cases, in situ measurements added little information to preoperative scintigraphy and surgical findings. The very high T/B ratios seen in MC tumours and some EPTs seem promising for future radiotherapy via somatostatin receptors.

Carcinoid Tumor↗

Development of a fast neutron spectrometer composed of silicon-SSD and position-sensitive proportional counters.

A new fast neutron spectrometer has been developed. The spectrometer is composed of a silicon surface barrier detector and three position-sensitive proportional counters with methane gas working as counting gas and a radiator. A collimated incident neutron interacts with a hydrogen atom in the methane gas to generate a recoil proton. The position information on the path of the recoil proton obtained from the three position-sensitive proportional counters gives the recoil angle. In the meanwhile, the energy of the recoil protons is measured with the three proportional counters and the silicon surface barrier detector. The characteristics of the spectrometer were evaluated with a monoenergetic neutron beam. The best energy resolution was 1.8% for 5.0 MeV neutrons.

Computer Simulation↗

The use of 3H-gamma-aminobutyric acid for transport studies with isolated nerve-terminals from rat brain.

Isolated synaptosomes were used to study the problem of net accumulation of neurotransmitters. The time-course and the kinetics of exogenous and endogenous GABA transport were studied by liquid-scintillation counting and HPLC-amino acid analysis respectively. Different pools of GABA were suggested by a 6-fold difference in tissue-to-medium-ratio of endogenous vs. exogenous GABA. Net accumulation, exchange and net efflux of GABA was found to be a function of the GABA concentration in the incubation medium. The Kms for net accumulation and for 3H-GABA accumulation were 2.68 +/- 1.16 and 6.19 +/- 1.26 microM respectively, whereas the Vmaxs were 5.9 +/- 4.9 and 134 +/- 13 pmol/mg w.w. min respectively. This means that the transport studies which use exogenous substances (e.g. 3H-GABA) considerably overestimate the transport by overlooking the magnitude of the counter transport.

4-Aminobutyrate Transaminase↗

The inhibitory effect of hCG on counter current transfer of GnRH and the presence of LH/hCG receptors in the perihypophyseal cavernous sinus--carotid rete vascular complex of ewes.

The existence of the hormone passage from venous blood into arterial blood in the area of the perihypophyseal vascular complex has been demonstrated in some mammals, but its mechanism has not been defined. To study the regulatory mechanism we infused hCG into perihypophyseal cavernous sinus of ovariectomized, conscious ewes to test if the hCG would affect putative LH/hCG receptors and inhibit counter-current transfer of GnRH from the venous cavernous sinus to the arterial carotid rete. The latter study was done on an isolated head model. Ewes were ovariectomized in mid-anestrus and, after 4 to 5 wk were used in the experiments. On the day of experiment ewes were treated intramuscularly with estradiol benzoate or oil vehicle, and 18 to 20 h later were infused either with a multielectrolyte solution or hCG for 2 h via the venae angularis oculi. Immediately thereafter the ewes were anesthetized and exanguinated, and subsequently decapitated. The isolated head was perfused with Dextran in multielectrolyte. The 125I-GnRH was infused into the cavernous sinus via the venae angularis oculi for 5 min; contemporaneous samples were taken from the carotid rete and both jugular veins at 1-min intervals. Transfer of 125I-GnRH from the cavernous sinus to the carotid rete was inhibited by hCG in ewes pretreated with estradiol benzoate but not with oil (P<0.005). We collected tissue samples from the vascular complex of the cavernous sinus and carotid rete of cyclic ewes to determine the presence of LH/hCG receptors. In situ hybridization showed the presence of LH/hCG receptor mRNA transcripts in the walls of both arterial and venous compartments of the cavernous sinus-carotid rete complex, and immunohistochemistry revealed the presence of receptor proteins. These novel findings confirm previously obtained data suggesting that LH is a modulatory factor for the counter-current transfer of neuropeptides from the venous blood of the cavernous sinus to the arterial blood supplying the brain and hypophysis. The LH could modulate 125I-GnRH transfer acting directly on the vascular smooth muscle.

Animals↗

Measurement of 24 hour whole body retention of 99Tcm-diphosphonate by a single thyroid probe.

In a comparative study with a thyroid probe and a whole body counter (WBC) we found that whole body retention (WBR) (2 h and 24 h) may be correctly obtained using a single probe, provided that measurements are taken carefully. With the detecting geometry presented, the single probe yielded only a slightly higher WBR than the WBC (less than 3 percentage points). We conclude that the method is capable of differentiating between pathological and normal WBR values.

Diphosphonates↗

High counting rates from 125I in radioimmunoassays.

Responses from one manual and four automatic gamma counters for assaying (125)I were compared. The resolution times quoted by manufacturers when applied in a standardized correction formula to obtain true counts from observed counting rates above 10(4) counts per second appeared to be inadequate. The need to investigate the errors associated with high counting rates for all instruments and electronic settings employed to determine (125)I in radioimmunoassays is emphasized.

Half-Life↗

Thallium-201: quantitation of right ventricular hypertrophy in chronically hypoxic rats.

Sprague Dawley rats were divided into two groups. Ten were kept in room air and 10 in hypobaric hypoxia (air at 380 mm Hg). After two weeks all were injected intravenously with 50 muCi of 201Tl and sacrificed. The right and left ventricles were separated, weighed, and measured for radioactivity in a gamma well counter. Left and right ventricular mass ratios (MR) correlated with 201Tl radioactivity ratios (TAR) in both control and hypoxic rats: r = 0.962 where MR = 0.863 TAR + 0.27. Myocardial 201Tl uptake reflects and quantitates normal and abnormal ventricular mass, the abnormal mass in this model consisting of right ventricular hypertrophy associated with hypoxic pulmonary hypertension.

Animals↗