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A new scintigraphic technique for assessment of right atrial function.

Gated radionuclide imaging with 99mTc-labeled red blood cells was employed to assess changes in right atrial (RA) volume in 17 subjects. Studies were repeated within two hours in five of 12 normal subjects and at two and ten days after infarction in five patients. Time-activity curves were generated for the RA and right ventricle (RV) from variable regions of interest defined by automatic edge detection. The RA time-activity curve exhibited four phases: filling, early emptying, equilibration, and late emptying. Repeated measurements of RA early emptying rates correlated closely in normals (r = 0.93). Early RA emptying and RV filling rates corresponded closely (r = 0.89). In four patients with infarction, the RA emptying rate was slowed on the first study but had normalized by 10 days. In a patient with inferior infarction and suspected RV infarction, the RA emptying rate was depressed and remained so for 10 days. Thus, relative changes in right atrial volume can be assessed reproducibly by a radionuclide technique, which is relatively independent of geometric assumptions. This technique offers great promise as a method to assess atrial function in health and disease.

Adult↗

The nonuniformity of antibody distribution in the kidney and its influence on dosimetry.

The therapeutic efficacy of radiolabeled antibody fragments can be limited by nephrotoxicity, particularly when the kidney is the major route of extraction from the circulation. Conventional dose estimates in kidney assume uniform dose deposition, but we have shown increased antibody localization in the cortex after glomerular filtration. The purpose of this study was to measure the radioactivity in cortex relative to medulla for a range of antibodies and to assess the validity of the assumption of uniformity of dose deposition in the whole kidney and in the cortex for these antibodies with a range of radionuclides. Storage phosphor plate technology (radioluminography) was used to acquire images of the distributions of a range of antibodies of various sizes, labeled with 125I, in kidney sections. This allowed the calculation of the antibody concentration in the cortex relative to the medulla. Beta-particle point dose kernels were then used to generate the dose-rate distributions from 14C, 131I, 186Re, 32P and 90Y. The correlation between the actual dose-rate distribution and the corresponding distribution calculated assuming uniform antibody distribution throughout the kidney was used to test the validity of estimating dose by assuming uniformity in the kidney and in the cortex. There was a strong inverse relationship between the ratio of the radioactivity in the cortex relative to that in the medulla and the antibody size. The nonuniformity of dose deposition was greatest with the smallest antibody fragments but became more uniform as the range of the emissions from the radionuclide increased. Furthermore, there was a strong correlation between the actual dose-rate distribution and the distribution when assuming a uniform source in the kidney for intact antibodies along with medium- to long-range radionuclides, but there was no correlation for small antibody fragments with any radioisotope or for short-range radionuclides with any antibody. However, when the cortex was separated from the whole kidney, the correlation between the actual dose-rate distribution and the assumed dose-rate distribution, if the source was uniform, increased significantly. During radioimmunotherapy, the extent of nonuniformity of dose deposition in the kidney depends on the properties of the antibody and radionuclide. For dosimetry estimates, the cortex should be taken as a separate source region when the radiopharmaceutical is small enough to be filtered by the glomerulus.

Animals↗

Diuretic radionuclide urography.

Diuretic radionuclide urography is a modification of conventional renography which utilizes the administration of intravenous furosemide to distinguish dilated, non-obstructed, hydronephrotic systems from those with significant mechanical obstruction. Diagnostic patterns are derived from computer generated time-activity histograms that depict the accumulation and washout of radiotracer before and after diuretic injection. In dilated but non-obstructed systems, diuresis produces a decline in activity. In obstructed systems, there is a failure of radiotracer washout in response to diuresis and no decline in activity is observed. The procedure is applicable to patients of all ages with suspected upper urinary tract obstruction. Clinical and experimental data support the accuracy and utility of this methodology and define its limitations and pitfalls.

Animals↗

Radiocaesium in mushrooms from northeast Italy, 1986-2002.

Late in the summer of 1986, the Health Physics Departments of Pordenone, Udine and Trieste, entrusted with monitoring radioactivity in the environment and food as a consequence of the Chernobyl accident, started noticing high concentrations of radionuclides--especially radiocaesium--in mushroom samples coming from different areas of the Friuli Venezia Giulia region (northeast Italy). To date, the authors have conducted 14 annual rounds of sampling and gamma spectrometry measurements on mushrooms, generating a total of over 2250 samples belonging to more than 300 species, which were picked in about 30 stations in the region. This surveys the main results from 15 years of macromycetes radiocontamination analysis in the region, the still unsolved problems, and hypotheses for future work.

Agaricales↗

Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.

For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.

Animals↗

Quantitative phase analysis of exercise radionuclide left ventriculography in normals and patients with coronary artery disease.

Using multigated radionuclide ventriculography (RNV), the left ventricular (LV) phase histogram (PH) was used to quantitate LV synchrony at rest and at submaximal and maximal supine exercise in 10 normal and 10 coronary (CAD) patients. Each LV PH was obtained by masking the phase image with an LV region, generated semiautomatically and modified if necessary to minimize ambiguity of LV delineation. The shape and spread of each histogram was characterized by its standard deviation (SD) and skewness (SK). Normals had a tight resting PH with slight negative skewness (SD = 9.06 +/- 0.22 (mean +/- SEM; SK = -0.53 +/- 0.05). CAD patients had a wider resting PH with a larger SD and a significantly more positive skewness reflecting greater contractile asynchrony (SD = 16.53 +/- 2.26; SK = 0.35 +/- 0.22). With exercise the PH distribution for the normals remained tight (SD = 8.1 +/- 0.24) while SK changed little (SK = -0.29 +/- 0.04). In contradistinction, with exercise CAD patients markedly increased the spread of their LV PH (SD = 27.42 +/- 3.77) and increased the number of late pixels (SK = 0.75 +/- 0.15). It is concluded that quantitative PH analysis is a useful adjunct for the analysis of regional asynergy during resting or exercise radionuclide left ventriculography.

Coronary Disease↗

Automatic analysis of left ventricular ejection fraction using stroke volume images.

The purpose of this study was to analyze, validate, and report on an automatic computer algorithm for analyzing left ventricular ejection fraction and to indicate future applications of the technique to other chambers and more advanced measurements. Thirty-eight patients were studied in the cardiac catheterization laboratory by equilibrium radionuclide ventriculography and concurrent contrast ventriculography. The temporal and spatial behavior of each picture element in a filtered stroke volume image series was monitored throughout the cardiac cycle. Pixels that met specific phase, amplitude, and derivative criteria were assigned to the appropriate chamber. Volume curves were generated from regions of interest for each chamber to enable calculation of the left ventricular ejection fraction. Left ventricular ejection fractions showed a good correlation (r = 0.89) between the two techniques. Ejection fractions ranged between 0.12 and 0.88, showing a wide range of application. It is concluded that automatic analysis of left ventricular ejection fraction is possible using the present algorithm and will be useful in improving the reproducibility and providing more accurate information during exercise protocols, pharmaceutical interventions, and routine clinical studies.

Cardiac Output↗

DUNBID, the Delft University neutron backscattering imaging detector.

In the search for low-metallic land mines, the neutron backscattering technique may be applied if the soil is sufficiently dry. An advantage of this method is the speed of detection: the scanning speed may be made comparable to that of a metal detector. A two-dimensional position sensitive detector is tested to obtain an image of the back scattered thermal neutron radiation. Results of experiments using a radionuclide neutron source are presented. The on-mine to no-mine signal ratio can be improved by the application of a window on the neutron time-of-flight. Results using a pulsed neutron generator are also presented.

Explosions↗

Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model.

Meta-tetrahydroxyphenylchlorin (m-THPC) and 5-aminolaevulinic acid (5-ALA) are two second-generation photosensitizers which are currently under investigation for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). So far, the experience with these photosensitizers for use within brain tumours is limited. We examined the distribution and retention of 14C-labelled m-THPC and [14C]5-ALA in the rat C6 glioma brain tumour model. After intraperitoneal injection of m-THPC (71,909 d.p.m. microl(-1); 0.16 mg ml(-1) m-THPC; 0.3 mg kg(-1)), the following activities were found after 36 h: brain tumour 223,664 d.p.m. g(-1), brain contralateral to the tumour side 2567 d.p.m. g(-1), liver 369,959 d.p.m. g(-1) and skin 55,197 d.p.m. g(-1); 100,000 d.p.m. corresponding to 0.22 microg of m-THPC. After 7 days, the concentration of m-THPC decreased to 76,277 d.p.m. g(-1) in tumour and 635 d.p.m. g(-1) in brain. The radioactivity after intravenous administration of [14C]5-ALA (23,079 d.p.m. microl(-1); 40 mg ml(-1); 120 mg kg(-1)) increased within 15 min (59,634 d.p.m. g(-1) in tumour, 17,427 d.p.m. g(-1) in brain); after 8 h only a small amount (3653 d.p.m. g(-1) in tumour) remained. Brain adjacent to the tumour was also found to have a higher uptake of 5-ALA. This study provides basic information for the use of m-THPC and 5-ALA in brain tumours. Because of the different pharmacokinetic and toxicological profile, we recommend m-THPC for PDT and 5-ALA for PDD. Clinical trials now have to prove the superior phototoxic properties of these second-generation photosensitizers.

Aminolevulinic Acid↗

Images for medical diagnoses.

Dr. Dietrich Meyer-Ebrecht provides a broad and helpful overview of the many techniques and latest trends in diagnostic imaging. Latest sensing technology is reviewed including: X-ray systems, ultrasound, thermography, radionuclide imaging, endoscopy, and optical methods. Approximate system cost ranges are indicated. This paper examines the technological trends in: sensors, imagers, hardcopy production, computer enhancement, storage, and communication of images. Dr. Meyer-Ebrecht describes three generations of computed tomographic scanners and alternative approaches to three-dimensional imaging. Image storage is presented as a major limitation of present technology. A view of future systems approaches envisions "picture bases" that will complement present data bases of hospital information systems. Integration of latest technology into diagnostic picture information systems will lead to advanced systems.

Computers↗

Comparison of oral iodine-131-cellulose and indium-111-DTPA as tracers for colon transit scintigraphy: analysis by colon activity profiles.

In 11 normal subjects and 11 patients with a clinical diagnosis of constipation, oral 131I-cellulose and 111In-DTPA were compared simultaneously as tracers for radionuclide colon transit scintigraphy. Visual assessment of the images revealed no differences between tracers. Quantitation was performed using total and segmental percent retention and the derived value of clearance half-time. In addition, profiles of the activity distribution along the length of the colon were generated and the mean position of the activity in the colon calculated. For all indices, the results were similar in both normal subjects and constipated patients when comparing tracers, although marked differences were present between normal subjects and constipated patients for each tracer. Indium-111-DTPA was easy to administer and dosimetry was more acceptable than for 131I-cellulose, especially in constipated patients. It is concluded that 111In-DTPA is the preferred tracer for oral colon transit scintigraphy.

Administration, Oral↗

Assessment of ventricular function in infants and children. Response to dobutamine infusion.

A method to assess ventricular functional reserve in infants and children unable to perform dynamic exercise was evaluated. Left ventricular ejection fraction was measured by radionuclide angiocardiography at rest and during infusion of dobutamine in 5-15 micrograms/kg/min dosages. The only side effects noted were arrhythmias in two patients, who had similar ectopy documented previously. Group left ventricular ejection fraction increased from 0.40 +/- 0.21 to a maximum of 0.49 +/- 0.24 (P less than 0.001). Left ventricular ejection fraction at 5 micrograms/kg/min (0.44 +/- 0.23) was not statistically different from that measured during infusion of dobutamine at 10 micrograms/kg/min (0.48 +/- 0.24). The six patients receiving anthracyclines, who had relatively low function at rest and increased function during dobutamine administration, were continued on their anticancer regimen without deteriorating in condition. Absolute values of left ventricular ejection fraction correlated best with the prognosis in patients with idiopathic dilated cardiomyopathy or structural abnormalities; six out of ten patients whose left ventricular ejection fraction never rose above 0.40 have either died or are in transplant protocols. Thus, study of left ventricular function can be performed easily during dobutamine infusion, generating valuable prognostic information.

Antineoplastic Agents↗

MABDOSE. II: Validation of a general purpose dose estimation code.

UNLABELLED: The MABDOSE software represents a general tool to assess internal radiation dose. A suite of tests are described that validate the dosimetry system's implementation. METHODS: The validation suite is divided among tests that verify target digitalization, tumor digitalization and organ replacement, cumulated activity calculation, random number generation, radiation transport, and dose calculation. RESULTS: A comparison between Reference Man organ volumes and MABDOSE organ volumes at (5 mm)3 resolution demonstrates volume correspondence within 10% save for ten organs having dimensions smaller than the target lattice resolution. An accounting of normal organ volume replaced by an arbitrary tumor volume indicates mass is conserved. A comparison between cumulated activities generated by MABDOSE and solutions obtained analytically demonstrates exact correspondence for curve-fitting algorithms. For mathematical modeling algorithms, cumulated activity solutions converge to their correct values provided sufficient data of high precision are input, accompanied by reasonable initial estimates of rate constants. A comparison of MABDOSE results with the MIRD 3 report demonstrates good agreement (<8% difference) in absorbed fractions for spheres at energies from 20 keV to 2.75 MeV. A comparison of MABDOSE results with the Cristy-Eckerman report demonstrates marginal agreement (specific absorbed fractions within a factor of 2 for all Reference Man organs) at simulation energies of 20, 50, and 100 keV. Lack of exact correspondence is attributed to volume digitalization errors, and to differences in cross-section libraries, interpolation schemes between cross-section data points, and random number generators. Finally, the doses reported by MABDOSE correspond to the correct algebraic combination of paired cumulated activities and "S" values. CONCLUSIONS: The MABDOSE program has been validated as a general purpose computation tool for use in internal radionuclide dosimetry.

Humans↗

Assessment of the end-systolic pressure-volume relationship in human beings with the use of a time-varying elastance model.

The analysis of left ventricular end-systolic pressure-volume relationships in human beings has been hindered by the lack of a practical method of serial volume assessment and by an imprecise definition of end-systole. Modifications of the end-systolic relationship that have been used to circumvent these problems have included the use of single-point end-systolic pressure-volume ratios, the use of peak systolic pressure/minimum ventricular volume points for end-systolic points, and the use of end-ejection as a marker for end-systole. To assess the correlation between the parameters generated by these modifications with the slope (Emax) and volume intercept (VO) of the end-systolic line as defined by Sagawa's model of time-varying elastance, simultaneous measurement of left ventricular pressure and gated radionuclide volume was made in 26 patients under various loading conditions and pressure-volume diagrams were constructed for each loading condition from 32 simultaneous pressure-volume coordinates. Two pressure-volume diagrams were recorded in 14 patients and three pressure-volume diagrams were recorded in 12 patients. Emax and VO were determined in all patients from the slope and volume intercept of the isochronic pressure-volume line with the maximum time-varying elastance as described by Sagawa's model and were designated true Emax and true VO, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

[Evaluation of additional absorbed radiation dose from radioactive impurities in radiopharmaceuticals].

The additional absorbed radiation doses to total body from radioactive impurities in radiopharmaceuticals were estimated for a total of 10 samples (i.e., 99mTc generator eluates, 99mTc solutions, 67Ga, 81mKr generator eluates, 111In, 123I, 201Tl, 75Se, 197Hg, 198Au) selected from commonly used radiopharmaceuticals. The radioactive impurities in radiopharmaceuticals used in this estimation were previously identified. The radiation doses were calculated according to the MIRD procedures, assuming each radionuclide to be uniformly distributed throughout the body. In the case of the cyclotron-produced radioisotopes and 198Au, the additional total body absorbed doses from impurities were found to be rather high: 280% for 123I, 55% for 81mKr, 5% for 198Au, 4% for 111In and 2% for 201Tl. The absorbed doses due to impurities in the other radioisotopes were less than 1%.

Drug Contamination↗

Phase analysis of gated blood pool scintigraphic images to localize bypass tracts in Wolff-Parkinson-White syndrome.

The ability of radionuclide techniques to localize bypass tracts in patients with Wolff-Parkinson-White syndrome to sites around the atrioventricular (AV) ring using a three view triangulation method was investigated. In 17 patients with Wolff-Parkinson-White syndrome, phase images were generated from gated blood pool scans using the first Fourier harmonic of the time-activity curve of each pixel. In addition, the difference between left and right ventricular mean phase angles was calculated for each patient and for 13 control subjects. Bypass tracts were localized to one or more sites on a 10 site grid schematically superimposed on the AV ring (Duke grid) by electrophysiologic study in all patients and by intraoperative mapping in 7 of the 17 patients. These same 10 anatomic sites were projected onto three scintigraphic views and the site of earliest ventricular phase angle was located in each view. The 10 sites around the AV ring were divided into two anatomic groups: free wall and septal/paraseptal. Phase image locations correlated with electrophysiologic locations within one grid site in 11 of 11 patients with free wall tracts and were confirmed at surgery in 5 of the 11. In five of six patients with septal/paraseptal tracts, electrophysiologic study could not localize the bypass tract to one site, whereas phase images localized two of the five as free wall adjacent to the septum, one as paraseptal and two as true posteroseptal. One posteroseptal site was confirmed at surgery. In one patient, in whom phase image analysis and electrophysiologic study showed different sites, existence of both tracts was confirmed at surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Technegas for inhalation lung imaging.

Technegas, an aerosol generator recently devised in Australia, produces aerosol particulates called 'technegas' which have characteristics of both an aerosol and a gas. The majority of the particulate is below 200 nm in size as measured by electron microscopy. Four normal subjects and 31 patients with various lung diseases were studied by imaging the lungs following inhalation of technegas. The penetration of inhaled technegas to the lung periphery was excellent; the average alveolar deposition ratio (ALDR) was 85%. Comparative studies with lung images obtained either with an ultrasonic nebulizer or jet nebulizers also confirmed better penetration of inhaled technegas to the lung periphery. There was no significant statistical difference in the ALDRs between normals and patients. Aerosol studies were comparable to perfusion counterparts, and evaluation of regional ventilatory status was greatly facilitated. Because of the large ALDR and the low airway deposition ratio (ADR), actual imaging could be done not only immediately after aerosol inhalation but also some time later without losing too much radioactivity from the lungs. One disadvantage was that technegas immediately after generation was anoxic.

Administration, Inhalation↗