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PubMed1986

Radionuclide assessment of left ventricular function in hypertrophic cardiomyopathy.

To determine the relationship of left ventricular function and ventricular tachycardia, 48 hour ECG monitoring and technetium-99m gated equilibrium radionuclide angiography were performed in 84 consecutive patients with hypertrophic cardiomyopathy and sinus rhythm. Measurements of ejection fraction (EF), peak ejection rate (PER, edv/s), peak filling rate (PFR, edv/s) and time to peak filling rate (PFR, ms) were derived from radionuclide activity time curves generated from data acquired in list-mode. Left ventricular function was compared in patients with and without ventricular tachycardia. Left ventricular ejection fraction was significantly lower in 16 patients with ventricular tachycardia compared to 68 patients without (67 +/- 17 vs 78 +/- 10, P less than 0.05) and time to peak filling rate was significantly prolonged (152 +/- 32 vs 120 +/- 36, P less than 0.05). Thus patients with hypertrophic cardiomyopathy at greatest risk of sudden death had significant impairment of systolic and diastolic left ventricular function.

Adolescent↗
PubMed1996

Radionuclide photon dose kernels for internal emitter dosimetry.

Photon point dose kernels and absorbed fractions were generated in water for the full photon emission spectrum of each radionuclide of interest in nuclear medicine, by simulating the transport of particles using Monte Carlo. The kernels were then fitted to a mathematical expression. Absorbed fractions for point sources were obtained by integrating the kernels over spheres. Photon dose kernels and absorbed fractions were generated for the following radionuclides: I-123, I-124, I-125, I-131, In-111, Cu-64, Cu-67, Ga-67, Ga-68, Re-186, Re-188, Sm-153, Sn-117m, Tc-99m. The Monte Carlo simulation was verified by comparing the dose kernels to published monoenergetic photon kernels. Further validation was obtained by generating an I-125 brachytherapy seed kernel and comparing it with published data. Since Monte Carlo simulation was initialized by sampling from the complete photon spectra of these radionuclides, interpolation between monoenergetic kernels and absorbed fractions was not required. The absorbed-fraction due to uniform spherical distributions can be directly applied for use in internal dosimetry. In addition, the kernels can be used as input for three-dimensional internal dosimetry calculations.

Brachytherapy↗
PubMed1999

Targeted delivery of radiolabeled imaging and therapeutic agents: bifunctional radiopharmaceuticals.

Clinical application of radioactive diagnostic and therapeutic agents constitutes one of the great advances in noninvasive medicine, nuclear medicine. The radioactive agents used in the nuclear medical field are called "radiopharmaceuticals," and are required to exhibit high and specific localization of radioactivity into target tissue. Among radionuclides used in radiopharmaceuticals, radiometals such as 99mTc and (111)In have received much attention because of their nuclear physical characteristics and widespread availability. However, since these metallic elements are not constituents of bioactive molecules, they cannot simply replace common constituent atoms in biologically interesting compounds. Thus, demand for biospecific radiopharmaceuticals constitutes a great challenge in rational design of biologically active molecules labeled with metallic radionuclides, and evolves into a generation of bifunctional radiopharmaceuticals. Molecules contain both a biologically active site and a chelating group for binding the metallic radionuclide in which attachment of a chelating group does not affect the inherent biospecificity of the mother compound. This paper describes recent progress in research of macro- and small-molecular bifunctional radiopharmaceuticals for targeted diagnosis and therapy.

Animals↗
PubMed1989

The development of alpha-emitting radionuclide lead 212 for the potential treatment of ovarian carcinoma.

alpha-Emitting radionuclides may be an effective alternative treatment against ovarian carcinoma because they have short half-lives and are densely ionizing, with high linear energy transfer to a depth of several cell diameters without requiring cellular oxygenation. One radionuclide that has been generated and tested in our laboratory in vitro and in vivo is lead 212 (212Pb). Intraperitoneal instillation of 212Pb prolonged survival and totally eradicated tumor in 24% of mice inoculated with the extremely virulent Ehrlich ascites-producing tumor. In vitro 212Pb was two to four times more effective in killing human ovarian cancer cells than x-rays. Irradiation with 212Pb increased the radiosensitivity and chromosomal aberrations of cells. In dogs, intraperitoneal instillation of 2.6 mCi of ferrous hydroxide tagged with 212Pb caused no significant toxicity. It appears that alpha-emitting radionucides such as 212Pb have the potential to be a new and potent treatment of ovarian carcinoma and could be effective in cases that are resistant to conventional chemotherapy or x-ray therapy.

Animals↗
PubMed1993

Use of single photon emission computed tomography in aerosol studies.

Single photon emission computed tomography (SPECT) has distinct advantages over the conventional planar imaging technique in generating more information about radionuclide distribution within the body. The general application of SPECT in lung studies has been extensive, but its specific use in aerosol research is still uncommon. This review focuses on the applications, the advantages and limitations, and the potential of quantification of SPECT in aerosol studies.

Administration, Inhalation↗
PubMed1987

Comparative uptake from sea water and tissue distribution of 60Co in marine mollusks.

Five different species of marine mollusks, Mytilus galloprovincialis Lmk., Tapes decussatus L., Cerastoderma (Cardium) edule (L.), Donax vittatus (da Costa) and Patella vulgata L., were exposed to 60Co-labelled sea water under laboratory conditions. After a 1-mo exposure, tested species reached different whole-body 60Co concentration factors (CF) over radioactive sea water of 73 +/- 27, 22 +/- 10, 84 +/- 25, 6.3 +/- 1.4 and 31 +/- 10, respectively, which are not dependent upon the size of mollusks. Equations for the experimental uptake curves, obtained using a multi-exponential model, indicate that 60Co uptake by mollusks involves two or three compartments, according to the species. In all species, the larger compartments turn over with long biological half-lives (24-251 d), dependent upon species. At the beginning of the experiment, 60CoCl2 added to sea water was mainly in cationic forms. These forms were progressively converted into anionic plus neutral forms most likely due to complex formation with organic ligands. With time this physico-chemical evolution had a lowering effect on 60Co bioaccumulation by mollusks. Analysis of 60Co in tissues revealed that Donax shell and mantle do not accumulate the radionuclide in great quantities, generating the low whole-body concentration factor found. In contrast, shell and mantle from all other species displayed variable but high CFs. Shell by itself accounts for more than half of the 60Co whole-body burden. Among soft tissues, gills and viscera displayed the highest CF and muscle the lowest. From these experiments, one may conclude that significant differences among species do exist regarding Co bioaccumulation potential. The wide range in Co CF values for mollusks found in the literature is also largely supported by interspecific differences actually existing.

Animals↗
PubMed1989

Kinetics of copper-PTSM in isolated hearts: a novel tracer for measuring blood flow with positron emission tomography.

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) ([Cu]PTSM) has shown potential as a flow tracer and can be labeled with the generator-produced positron emitting radionuclide 62Cu as well as with other copper radioisotopes. To define the myocardial handling of [Cu]PTSM, the externally detected single pass extraction and retention of [67Cu]PTSM was characterized after bolus administration in 12 isolated rabbit hearts perfused with erythrocyte-enriched modified Krebs-Henseleit buffer which permitted physiologic flow rates. The myocardial residual (extraction) fraction at control flow rates (approximately 1.5 ml/g/min) was 45 +/- 7(s.d.)% (n = 12), and was invariate with ischemia (flow = 0.15 ml/g/min, n = 4), hyperemia (flow = 3 ml/g/min, n = 4) or with hypoxia induced by perfusion at control flow rates with hypoxic buffer (n = 4) (residual fraction 45 +/- 20, 43 +/- 8, and 49 +/- 8%, respectively, p = N.S.). Once extracted, the tracer was retained with a biologic t1/2 of greater than 3600 min in all groups. The high single-pass extraction, which is not influenced by flow, and the prolonged retention of this tracer under diverse conditions indicate that [Cu]PTSM could be a useful tracer for measuring blood flow with positron emission tomography.

Animals↗
PubMed1999

An 225Ac/213Bi generator system for therapeutic clinical applications: construction and operation.

A method for construction and operation of an 225Ac/213Bi generator capable of producing 25-100 mCi of 213Bi suitable for clinical antibody labeling is described. The generator has been designed to have an effective lifetime of several weeks, producing up to six therapeutic doses of radionuclide per day. To date, 57 clinical doses have been prepared and injected into patients using the described 213Bi generator. Factors such as radiation damage, radioprotection, iodide eluate chemistry, radiolabeling chemistry and radionuclide purity are addressed.

Actinium↗
PubMed1988

An improved tungsten-178/tantalum-178 generator system for high volume clinical applications.

Clinical utilization of the multiwire gamma camera (MWGC) requires low-energy radionuclides. The short-lived (9.3 min) tantalum-178 (178Ta) is ideally suited for the MWGC and can be produced from long-lived (21.7 day) tungsten-178 (178W) by a previously reported 178W/178Ta generator. This generator, however, is limited by sharp increase in breakthrough after elution of only 30-60 column-volumes. To optimize the 178W/178Ta generator for clinical use, varying eluant acid concentrations were evaluated. A reduced (from 0.1 to 0.03N) HCI concentration in the eluant, coupled with low operating temperatures (3 to 5 degrees C) allowed high (40 to 60%) 178Ta yield. Minimal 178W breakthrough (less than .01%) resulted, even after elution of more than 200 column-volumes. Each of six tested generators provided sterile, high activity (up to 100 mCi) 178Ta elutions for more than 30 days. Radiation dosimetry was estimated utilizing both human and animal biodistribution data. The whole body (critical organ) dose in adults and neonates were 1/20 (1/21) and 1/19 (1/50) respectively relative to that of technetium-99m (99mTc) as sodium pertechnetate. The optimized 178W/178Ta generator provides a commercially practical, safe source of low-energy radioisotope for the MWGC with substantial dosimetry advantages over 99mTc.

Animals↗
PubMed2001

Monitoring methods and dose assessment for internal exposures involving mixed fission and activation products containing actinides.

Internal dose assessment for intakes of radionuclide mixtures is a difficult task. When the radionuclide mixture contains both the easy to detect gamma emitters, e.g., 60Co and 95Zr, and difficult to detect alpha emitters such as 239Pu and 241Am, a single monitoring method, such as in-vivo counting, is inadequate for detection and dose assessment. Recent experience with task related monitoring for such radionuclide mixtures at Ontario Power Generation CANDU nuclear power plants has offered an opportunity to review this topic and suggest a strategy for monitoring that involves a combination of in-vivo and in-vitro methods. Using the radionuclide composition data in a mixture from an actual case as an example, this paper describes a monitoring strategy for mixed fission and activation products, including the advantages and pitfalls of reliance on surrogate radionuclides for signaling the presence of actinides in the mixture. The described monitoring strategy is consistent with the recommendations of ICRP Publication 78, which advocates a "combination of techniques so as to make the best possible evaluation of an unusual situation, for example, a programme of both body activity and excreta measurements." The use of experience and professional judgement for interpreting the combined in-vivo and in-vitro data for interim and ultimate intake and dose assessment is discussed and emphasized.

Actinoid Series Elements↗
PubMed1982

Cyclotron production of 128Cs (3.62 min). A new positron-emitting radionuclide for medical applications.

The cyclotron production of the short-lived positron emitter 128Cs (3.62 min) from its longer-lived parent 128Ba (2.42 d), based upon the 133Cs(p, 6n) 128Ba leads to 128Cs reaction (Q = -43.98 MeV), has been studied. Cesium-128 has potential applications in positron tomography, particularly for imaging the myocardium and/or for the assessment of regional blood flow. Thick-target yields (mCi/muAh) and cross sections (mb) for 128Ba, 131Ba, 129Cs and 132Cs were measured in the 67-36 MeV proton-energy region. Cyclotron production of 128Ba-128Cs (transient equilibrium) was measured as 3.1 mCi/muAh at end of bombardment (EOB) with a 2.32 g cm-2 thick CsCl target with a proton entrance energy of 67 MeV and exit energy of 54 MeV. Target-radiochemistry using ion-exchange methods allow the preparation of a generator-type system from which high-radionuclidic purity, radiopharmaceutical quality, no-carrier-added 128Cs can be obtained for immediate administration. In addition, with proper radiochemical handling of the 128Ba-128Cs generator, no-carrier-added, high-purity 129Cs (32.35 h, 372 keV, 32%) can also be produced for use in research applications.

Cesium Radioisotopes↗
PubMed2005

Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methods.

The article reviews the background and current status of pretargeting for cancer imaging and therapy with radionuclides. Pretargeting procedures were introduced approximately 20 years ago as an alternative to directly radiolabeled antibodies. Because they were multistep processes, they were met with resistance but have since progressed to simple and improved procedures that could become the next generation of imaging and therapy with radionuclides. The separation of the radiolabeled compound from the antibody-targeting agent affords pretargeting procedures considerable flexibility in the radiolabeling process, providing opportunities for molecular imaging using gamma- or positron-emitting radionuclides and a variety of beta- and alpha-emitting radionuclides of therapeutic applications. Pretargeting methods improve tumor/nontumor ratios, exceeding that achieved with directly radiolabeled Fab' fragments, particularly within just a few hours of the radionuclide injection. In addition, tumor uptake exceeds that of a Fab' fragment by as much as 10-fold, giving pretargeting a greatly enhanced sensitivity for imaging. Advances in molecular biology have led to the development of novel binding proteins that have further improved radionuclide delivery in these systems. Studies in a variety of hematologic and solid tumor models have shown advantages of pretargeting compared with directly radiolabeled IgG for therapy, and there are several clinical studies under way that are also showing promising results. Thus, the next generation of targeting agents will likely employ pretargeting approaches to optimize radionuclide delivery for a wide range of applications.

Animals↗
PubMed1979

99mTechnetium pyridoxylidene glutamate imaging in visceral heterotaxy (Ivemark's syndrome).

A two and one-half year old boy with complex congenital heart disease had Howell-Jolly bodies in his blood raising the possibility of the asplenia syndrome. A 99mTc-sulfur colloid liver-spleen scan was reported normal, but the right lobe of the abnormally reversed liver was mistaken for the spleen. The diagnosis of visceral heterotaxy (Ivemark's syndrome) was established after scanning the patient with a new radiopharmaceutical, 99mTechnetium pyridoxylidene glutamate. The agent clearly demonstrated a left-sided gall bladder, and on comparison with the sulfur colloid scan it was established that asplenia was present. Radionuclide imaging with the new generation of hepatobiliary agents is a reliable method to document asplenia and is useful in studying patients with visceral heterotaxy.

Child, Preschool↗
PubMed1981

A noninvasive method for measuring portal venous/total hepatic blood flow by hepatosplenic radionuclide angiography.

Radionuclide angiography was used to generate first-pass radioactivity vs. time curves for the left heart, right hepatic lobe, right lung, spleen, and both kidneys following rapid intravenous injection of 20 mCi (740 MBq) of 99mTc-pertechnetate. Seven normal subjects were examined as well as 57 cirrhotic patients, who also underwent angiographic grading of portal venous perfusion. For analysis, two time points were identified: (a) t0, when 99mTc first entered the liver (the initial rise of either curve); and (b)tc, when 99mTc was maximal in abdominal organs (the renal peak). Analysis was based on the slopes of the two phases of the hepatic curves t0 + 7 seconds and Tc + 7 seconds; this time selection permitted analysis of all curves. The hepatic perfusion index (HPI) = slope (tc + 7 secs)/slope (t0 + 7 secs) + slope (tc + 7 secs). The mean HPI for the normal subjects was 66% +/- 7; for the cirrhotic patients with angiographic Grades I, II, III, and IV, the HPI was 52% +/- 9, 37% +/- 6, 15% +/- 7, and 3% +/- 4, respectively. Correlation between HPI and angiography was significant (p less than 0.001). This method offers a readily available, rapid, relatively inexpensive, and quantitative method of grading the ratio of portal venous to total hepatic blood flow.

Adult↗
PubMed1993

Evaluation of copper-labeled bifunctional chelate-albumin conjugates for blood pool imaging.

62Cu(T1/2 = 9.8 min) is a generator-produced positron-emitting radionuclide with a half-life amenable to blood-pool imaging with PET. Three bifunctional chelates [cyclic anhydride of diethylenetriaminepentaacetic acid (cDTPAA), 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N ',N", N"'-tetraacetic acid (BAT), and p-carboxyethylphenylglyoxal-bis-(4N-methyl-thiosemicarbazone (CE-DTS)] were conjugated to HSA and labeled with 67Cu. The labeling efficiency of 67Cu-DTS-HSA was > 90%, whereas the labeling yields of 67Cu-DTPA-HSA and 67Cu-benzyl-TETA-HSA were less than 70%. Blood clearance and biodistribution of these three 67Cu-labeled conjugates were determined in rats. Of the three 67Cu-labeled bifunctional chelate-HSA conjugates, 67Cu-benzyl-TETA-HSA remained in the blood pool the longest, achieving stable blood levels at times longer than 24 h post-injection. The 67Cu radioactivity cleared the blood within 60 min post-injection of 67Cu-DTS-HSA, and within 10 min after administration of 67Cu-DTPA-HSA, indicating the dissociation of Cu2+ from these conjugates. Copper-labeled DTS-HSA achieved stable blood concentrations for at least 30 min post-injection and was therefore evaluated as a vascular imaging agent. DTS-HSA and benzyl-TETA-HSA were labeled with 62Cu and administered to a dog for blood-pool imaging using PET. Images were nearly identical to an image taken after administration of C15O. Because of the high labeling efficiency, DTS-HSA can be labeled with 62Cu without purification, making it more practical than 62Cu-benzyl-TETA-HSA as a blood-pool imaging agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Preparation of rhenium-188-tin colloid as a radiation synovectomy agent and comparison with rhenium-188-sulfur colloid.

As a generator-produced beta-emitting radionuclide, the importance of 188Re for radionuclide therapy is increasing rapidly. We prepared 188Re-tin colloid and compared its properties with 188Re-sulfur colloid. Labeling efficiencies reached >98% for tin colloid at 2 h and 89-94% for sulfur colloid at 3 h. All the preparations were stable for 72 h in water, serum, and synovial fluid. If labeled at higher temperature, the particle size of tin colloid increased. The residual radioactivity of 188Re-sulfur colloid in disposable polypropylene syringes after injecting mice was high (62.0+/-7.0%) due to its hydrophobic nature, while that of 188Re-tin colloid was low (2.9+/-1.6%). Although both 188Re-tin colloid and 188Re-sulfur colloid might be useful for radionuclide therapy, we conclude that 188Re tin colloid is more advantageous over 188Re sulfur colloid, due to higher labeling efficiency, control of the particle size, and lower residual activity in the injection syringes.

Animals↗
PubMed1998

An alternative approach to hot spot identification using in situ gamma spectrometry measurements on a grid.

We describe the application of a computer code developed to analyze data from a series of in situ gamma spectrometry measurements on a grid. The code was designed to be used as a tool when evaluating compliance with regulations that set limits on the size and magnitude of elevated activity areas (also known as "hot spots"). It calculates location and magnitude of potential elevated activity areas consistent with the data, and for each potential elevated area it generates a corresponding distribution of radionuclides in the soil. The algorithm uses a maximum entropy deconvolution of the data, followed by further analysis. A test case using data from actual field measurements is presented.

Entropy↗