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PubMed1981

Enhanced detection of metastatic liver disease by computerized flow scintigrams: concise communication.

The purpose of this study was to develop a method by which the sensitivity of radionuclide liver imaging for the detection of hepatic metastasis could be enhanced. Routine flow studies were performed before imaging by injecting the usual 2-3 mCl dose of Tc-99m sulfur colloid as a bolus and storing 30 2-sec images in a computer. With regions selected by light pen, curves were generated from the right lobe of the liver, the right kidney, and the descending aorta. The peak of the kidney curve was chosen as a marker to separate the arterial and venous phases on the liver curve. The average slopes of four points on the liver curve before this marker, and four after, were calculated and the ratio of the first slope to that of the second was defined as the arterialization index. In this study with 228 patients, the inclusion of this index raised the sensitivity from 85 to 100%.

Aorta↗
PubMed1981

Diuretic radionuclide renography and scintigraphy in the differential diagnosis of hydroureteronephrosis.

Conventional radionuclide renography has been modified to include a pharmacologic intervention by administration of intravenous furosemide. The procedure is applied in patients with hydroureteronephrosis to distinguish dilated, nonobstructed systems from those with significant mechanical obstruction. Diagnostic patterns are derived from computer-generated time-activity histograms that depict the accumulation of radiotracer prior to diuresis and in response to diuresis. In dilated, nonobstructed systems, increased urine flow following diuresis causes a decline or "washour" of activity. In significantly obstructed systems, there is a failure of tracer activity to decrease in response to diuresis. The procedure is applied most commonly in suspected ureteropelvic junction and ureterovesical junction obstruction. The significance of residual urinary tract dilatation following corrective surgery also can be readily assessed. The major current limitation to the technique is poor renal function with inadequate response of urine flow to diuresis.

Adolescent↗
PubMed2001

Colloids in the mortar backfill of a cementitious repository for radioactive waste.

Colloids are present in groundwater aquifers and water-permeable engineered barrier systems and may facilitate the migration of radionuclides. A highly permeable mortar is foreseen to be used as backfill for the engineered barrier of the Swiss repository for low- and intermediate-level waste. The backfill is considered to be a chemical environment with some potential for colloid generation and, due to its high porosity, for colloid mobility. Colloid concentration measurements were carried out using an in-situ liquid particle counting system. The in-house developed counting system with three commercially available sensors allowed the detection of single particles and colloids at low concentrations in the size range 50-5000 nm. The counting system was tested using suspensions prepared from certified size standards. The concentrations of colloids with size range 50-1000 nm were measured in cement pore water, which was collected from a column filled with a highly permeable backfill mortar. The chemical composition of the pore water corresponded to a Ca(OH)2-controlled cement system. Colloid concentrations in the backfill pore water were found to be typically lower than approximately 0.1 ppm. The specific (geometric) surface areas of the colloid populations were in the range 240 m2 g(-1) to 770 m2 g(-1). The low colloid inventories observed in this study can be explained by the high ionic strength and Ca concentrations of the cement pore water. These conditions are favourable for colloid-colloid and colloid-backfill interactions and unfavourable for colloid-enhanced nuclide transport.

Colloids↗
PubMed1992

The multichain interleukin-2 receptor: a target for immunotherapy.

Activation of resting T-lymphocytes induces synthesis of interleukin-2 (IL-2) and expression of cell surface receptors for this lymphokine. In contrast to resting normal T-cells that do not express high-affinity IL-2 receptors (IL-2R), abnormal T-cells of patients with leukemia-lymphoma, certain autoimmune disorders, and individuals rejecting allografts express this receptor. Exploiting this difference in receptor expression, antibodies to the IL-2 receptor have been used effectively to treat patients with leukemia and lymphoma. One approach is to use monoclonal antibodies produced in mice; the disadvantage is that they are highly immunogenic. In an effort to reduce the immunogenicity of the mouse monoclonal antibodies, monoclonal-antibody-mediated therapy has been revolutionized by generating humanized antibodies produced by genetic engineering in which the molecule is human except for the antigen-combining regions, which are retained from the mouse. Further, to increase its cytotoxic effectiveness, the monoclonal antibody has been armed with toxins or radionuclides. Alternatively, IL-2 itself has been linked to a toxin to kill IL-2 receptor-bearing cells. Thus, IL-2 receptor-directed therapy provides a new method for treating certain neoplastic diseases and autoimmune disorders and for preventing allograft rejection.

ADP Ribose Transferases↗
PubMed2003

Application of rhenium-188 HEDP in bone metastases therapy.

Radionuclide bone metastases therapy is a major achievement of nuclear medicine. Development of less radiotoxic and more effective radiopharmaceuticals is therefore a challenge for radiopharmacists and industry. This paper reviews the application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for bone metastases therapy.

Bone Neoplasms↗
PubMedDate not supplied

Design, synthesis, and evaluation of [188Re]organorhenium-labeled antibody fragments with renal enzyme-cleavable linkage for low renal radioactivity levels.

Renal localization of radiolabeled antibody fragments constitutes a problem in targeted imaging and radiotherapy. We have reported that Fab fragments labeled with 3'-[131I]iodohippuryl Nepsilon-maleoyl-lysine (HML) showed markedly low renal radioactivity levels even shortly after injection, due to a rapid and selective release of m-[131I]iodohippuric acid by the action of brush border enzymes. To estimate the applicability of the molecular design to metallic radionuclides, [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR-COOH) was conjugated with Nepsilon-tert-butoxycarbonyl-glycyl-lysine or Nepsilon-maleoyl-glycyl-lysine to prepare [188Re]CpTR-GK-Boc or [188Re]CpTR-GK. The cleavage of the glycyl-lysine linkage of the two compounds generates a glycine conjugate of [188Re]CpTR-COOH ([188Re]CpTR-Gly), which possesses in vivo behaviors similar to those of m-iodohippuric acid. The hydrolysis rate of the peptide bond in [188Re]CpTR-GK-Boc was compared with that in 3'-[125I]iodohippuryl Nepsilon-Boc-lysine ([125I]HL-Boc) using brush border membrane vesicles (BBMVs) prepared from rat kidneys. [188Re]CpTR-GK was conjugated to thiolated Fab fragments to prepare [188Re]CpTR-GK-Fab. The biodistribution of radioactivity after injection of [188Re]CpTR-GK-Fab was compared with that of [125I]HML-Fab and [188Re]CpTR-Fab prepared by conjugating N-hydroxysuccinimidyl ester of [188Re]CpTR-COOH with antibody fragments. While [188Re]CpTR-GK-Boc liberated [188Re]CpTR-Gly in BBMVs, [125I]HL-Boc liberated m-[125I]iodohippuric acid at a much faster rate. In addition, although [125I]HL-Boc was hydrolyzed by both metalloenzymes and nonmetalloenzymes, metalloenzymes were responsible for the cleavage of the peptide linkage in [188Re]CpTR-GK-Boc. In biodistribution studies, [188Re]CpTR-GK-Fab exhibited significantly lower renal radioactivity levels than did [188Re]CpTR-Fab. However, the renal radioactivity levels of [188Re]CpTR-GK-Fab were slightly higher than those of [125I]HML-Fab. The analysis of urine samples collected for 6 h postinjection of [188Re]CpTR-GK-Fab showed that [188Re]CpTR-Gly was the major radiometabolite. In tumor-bearing mice, [188Re]CpTR-GK-Fab significantly reduced renal radioactivity levels without impairing the radioactivity levels in tumor. These findings indicate that the molecular design of HML can be applied to metallic radionuclides by using a radiometal chelate of high inertness and by designing a radiometabolite of high urinary excretion when released from antibody fragments following cleavage of a glycyl-lysine linkage. This study also indicates that a change in chemical structure of a radiolabel attached to a glycyl-lysine linkage significantly affected enzymes involved in the hydrolysis reaction. Since there are many kinds of enzymes that cleave a variety of peptide linkages on the renal brush border membrane, selection of a peptide linkage optimal to a radiometal chelate of interest may provide radiolabeled antibody fragments that exhibit renal radioactivity levels similar to those of [131I]HML-labeled ones. The in vitro system using BBMVs might be useful for selecting an appropriate peptide linkage.

Animals↗
PubMed1975

Nontraumatic determination of left ventricular ejection fraction by radionuclide angiocardiography.

Previous reports have suggested that left ventricular ejection fraction can be assessed by recording the passage of peripherally administered radioactive bolus through the heart. The accuracy and validity of this technique were examined in 20 patients undergoing diagnostic cardiac catheterization. 99m-Tc-human serum albumin was injected via a central venous catheter into the superior vena cava and precordial activity recorded with a gamma scintillation camera interfaced to a small digital computer. A computer program was designed to generate time-activity curves from the left ventricular blood pool and to calculate left ventricular ejection fractions from the cyclic fluctuations of the left ventricular time-activity curve which correspond to left ventricular volume changes during each cardiac cycle. The results correlated well with those obtained by biplane cineangiocardiography (r equals 0.94) and indicated that the technique should allow accurate and reproducible determination of left ventricular ejection fraction. The findings, however, demonstrated that the time-activity curve must be generated from a region-of-interest which fits the left ventricular blood pool precisely and must be corrected for contributions arising from noncardiac background structures. This nontraumatic and potentially noninvasive technique appears particularly useful for serial evaluation of the acutely ill patient and for follow-up studies in nonhospitalized patients.

Adult↗
PubMed1990

Xenon-127m: a new radionuclide for applications in nuclear medicine.

Xenon-127m (127mXe) emits two gamma rays in cascade, with half-life of 69.2 +/- 0.9 sec. The first has the energy of 172.5 keV, and is emitted from the nucleus in 38% of the decays. The second gamma ray has the energy of 124.8 keV and is emitted from the nucleus in 69% of the disintegrations. Together they furnish 107 easily collimated gamma rays per 100 decays. Xenon-127m is generated readily by bombarding nearly saturated aqueous solutions of sodium or potassium iodide with 14-MeV protons. The 127mXe is swept out continuously, as it is produced, by bubbling helium upward through the solutions. Up to approximately 100 mci/l are obtained from the resulting mixture of gases. The 127mXe + helium is admixed with about five volumes of air (or oxygen) and then driven continuously to a scintillation camera located approximately 200 yd distant. When the mixture of gases is inhaled, high quality images of the lungs are obtained by means of an Anger scintillation camera.

Half-Life↗
PubMedDate not supplied

Assessment of left ventricular function during upright treadmill exercise with tantalum 178 and multiwire gamma camera.

BACKGROUND: Prior studies with first-pass radionuclide angiography (RNA) during treadmill exercise used a single-crystal (Anger) or multicrystal gamma camera and technetium 99m tracers. Motion correction, when done, used point sources, which limited correction to only plane movement. METHODS AND RESULTS: We examined the performance of a multiwire gamma camera (MWGC), generator-produced tantalum 178, and a novel method of motion correction during treadmill exercise testing. We studied 100 patients in whom rest and stress gated tomographic myocardial perfusion images were obtained. Eight patients were excluded because of incomplete data. There were 53 men and 39 women aged 52 +/- 12 years. The resting left ventricular (LV) ejection fraction (EF) was 61% +/- 12% by gated single photon emission computed tomography. Stress myocardial perfusion was normal in 83 patients and abnormal in 9 patients. The resting RNA EF in the upright position was 57% +/- 12% (r = 0.52, P = .0001 vs gated EF). At peak exercise, the EF by MWGC was 60% +/- 26% if uncorrected and 69% +/- 13% after motion correction. Among the 80 patients with normal perfusion and normal resting EF by gated single photon emission computed tomography, a normal response to exercise was seen in 52 (63%) without motion correction and 74 (89%) with motion correction (P < .05). CONCLUSION: Assessment of LV function is feasible with MWGC. The motion-corrected images significantly improved the results.

Algorithms↗
PubMed1996

Identification and screening evaluation of key historical materials and emission sources at the Oak Ridge Reservation.

In 1991, the State of Tennessee initiated a Health Studies Agreement with the U.S. Department of Energy. It included independent studies of possible adverse health effects in people living near the Oak Ridge Reservation resulting from releases of chemicals and radionuclides since 1942. A Dose Reconstruction Feasibility, the first of a planned sequence of initiatives to evaluate the potential for health effects, included application of screening methods to focus subsequent dose reconstruction and epidemiologic efforts on the materials and emission sources that have historically been most important. The feasibility study produced a history of operations that likely generated off-site releases from the X-10, K-25, Y-12, and S-50 plants, based on reviews of classified and unclassified records and interviews of active and retired workers. The availability of environmental monitoring and research data that would support dose reconstruction was also characterized. Quantitative emission and environmental contamination data were used to identify those materials and plant activities that should receive the highest priority in further health studies. Plausible exposure pathways were identified, and screening methods were used to identify the most important pathways and past activities that appear to be associated with the greatest health hazards. The materials and activities shown to have the highest potential for public health hazards are as follows: 1) The release of radioiodine [likely over 3.7 PBq (100,000 Ci)] to the air from radioactive lanthanum ("RaLa") processing at X-10 (now Oak Ridge National Laboratory) from 1944 through 1956; 2) The release of 137Cs and other radionuclides in liquid wastes from chemical separation activities at X-10; 3) The release of mercury to the air, soil, and surface waters from Y-12 lithium enrichment operations between 1950 and 1963. About 11,000,000 kg of mercury were handled at Y-12, and 910,000 kg were reported lost or unaccounted for; and 4) The release of polychlorinated biphenyls (PCBs) from machining oils, electrical equipment, and other sources in the Oak Ridge area. Based on the findings of the study, the Oak Ridge Health Agreement Steering Panel called for a dose reconstruction for radioiodine, mercury, PCBs, and radionuclides released from White Oak Creek and research into opportunities for analytic epidemiologic studies to identify adverse health effects in exposed populations.

Air Pollutants, Radioactive↗
PubMed2005

Dosimetry of 60/61/62/64Cu-ATSM: a hypoxia imaging agent for PET.

PURPOSE: Cu-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) is an effective marker for the delineation of hypoxic tissue. Dosimetry calculations by the established Medical Internal Radionuclide Dose (MIRD) approach were performed with both animal and patient data. METHODS: Human absorbed dose estimates extrapolated from rat data were based on the biodistribution of 61Cu-ATSM in adult rats. Eighteen tissues were harvested and time-activity curves generated. The measured residence times and the MIRD S-values for 60Cu-ATSM were used to estimate human absorbed doses. The biodistribution of the tracer was directly measured in five patients injected with approximately 480 MBq of 60Cu-ATSM and imaged by positron emission tomography (PET) with a whole-body protocol. The combined data from all patients were used to derive organ residence times, and organ doses were calculated by MIRD methodology for 60Cu-ATSM, 61Cu-ATSM, 62Cu-ATSM, and 64Cu-ATSM. RESULTS: Human absorbed dose estimates extrapolated from rat biodistribution data indicated that the kidneys appeared to be the dose-limiting organ (0.083 mGy/MBq) with a whole-body dose of 0.009 mGy/MBq. Based on the human PET imaging data, the liver appeared as the dose-limiting organ, with an average radiation dose of 0.064 mGy/MBq. The whole-body dose was 0.009 mGy/MBq and the effective dose was 0.011 mSv/MBq. CONCLUSION: These relatively small absorbed doses to normal organs allow for the safe injection of 500-800 MBq of 60Cu-ATSM, which is sufficient for PET imaging in clinical trials.

Absorption↗
PubMed1988

Forearm mineral content in normal men: relationship to weight, height and plasma testosterone concentrations.

We measured forearm bone mineral content by single photon absorptiometry together with height, weight and the plasma concentrations of testosterone, free testosterone and sex steroid binding globulin in 66 normal Caucasian males aged 29-46 years. Multiple regression analysis suggests that bone mineral content in either the dominant or the nondominant arm is correlated with weight and sex steroid binding globulin (p less than 0.05 for both parameters). The partial negative correlation of bone mineral content (corrected for weight and sex steroid binding globulin) with plasma testosterone failed to reach statistical significance (p = 0.07). The parsimonious regression equation which best explained the bone mineral content measurements in the nondominant forearm in these men was bone mineral content = 29.1-0.374 (plasma testosterone) + 0.383 (weight) + 0.220 (sex steroid binding globulin) with an R2 value of 29.7%. A similar equation was generated for the dominant arm.

Adult↗
PubMed1977

Large-field-of-view (LFOV) scintillation cameras.

Large-field-of-view scintillation cameras are general purpose, cost effective, imaging devices if one maximizes the use of the crystal with respect to the size of the object under study. This means using parallel-hole collimation for large-organ systems to reduce the number of views necessary to complete a study or to obtain a better appreciation of continuity of structure. A further increase in photon utization is gained for small-organ imaging with converging collimators, which produce images with superior resolution and sensitivity to that obtained with equivalent parallel-hole collimators. The disadvantages of converging collimators, including decreasing field of view and distortion with depth, have been insignificant in light of the advantages gained. Larger detectors with converging collimation result in much higher photon input rates to the scintillation crystal in routine clinical studies than has occurred in the past. This requirement places added burdens on electronic circuitry of the cameras. Count rate processing capabilities of 200,000 counts per second are currently available and are necessary for present generation first-pass cardiovascular studies.

Asthma↗
PubMed1995

Clinical applications of renal scintigraphy.

Nuclear medicine techniques for evaluating the kidney and urinary tract have evolved from pioneering studies with primitive radiopharmaceuticals and hand-held probe detectors to a sophisticated technology capable of providing important physiologic and anatomic information. Advances in nuclear medicine and computer technology over the past decade have resulted in improved, clinically useful scintigraphic studies to assist clinicians in examining patients who have diseases of the genitourinary tract. However, renal scintigraphy is a complex subject. Five different radiopharmaceuticals are available for scanning the kidneys, multiple quantitative indexes can be generated, and protocols may vary depending on the clinical setting. The focus of this review is practical: to summarize the clinical advantages and disadvantages of the different radiopharmaceuticals; to review quantitative indexes that help interpret images; and to review the role of radionuclide scintigraphy in patients with suspected obstruction, pyelonephritis, and renovascular hypertension.

Humans↗
PubMed1990

[Radioaerosol inhalation lung imaging using technegas].

Technegas generator using 99mTc-pertechnetate was tested on 4 normal subjects and 31 patients with various chest diseases including bronchogenic carcinoma, pneumonia, pulmonary tuberculosis, sarcoidosis, and so on. Technegas was inhaled from the RV to the TLC levels through the mouth with the nose clipped followed by breath-holding. Three deep breaths were enough to deposit 37-55.5 MBq (1 to 1.5 mCi) of technegas in the lungs. The average alveolar deposition ratio (ALDR) was 85% and penetration of inhaled technegas to the lung periphery was excellent. "Hot spots" or excessive radioactive deposition were also seen when there was airway obstruction. The former indicated the characteristic as gas and the latter, that as aerosol particles. Because of the large ALDR's the timing for imaging lungs after inhalation of technegas most likely indicated the intrapulmonary sites of effective ventilation, because respective inhalation and perfusion lung images resembled each other very much. The disadvantage of technegas was that it was anoxic right after generation.

Administration, Inhalation↗
PubMed2004

Sequence-specific DNA strand cleavage by 111In-labeled peptide nucleic acids.

Peptide nucleic acids (PNAs) bind tightly and sequence-specifically to single- and double-stranded nucleic acids, and are hence of interest in the design of gene-targeted radiotherapeutics that could deliver the radiodamage to designated DNA and/or RNA sites. As a first step towards this goal, we developed a procedure for incorporation of Auger electron-emitting radionuclide (indium-111) into PNA oligomers and studied the efficiency of PNA-directed cleavage of single-stranded DNA targets. Accordingly, diethylene triamine penta-acetic acid (DTPA) was conjugated to the lysine-appended mixed-base PNAs and sequence-homologous DNA oligomer with a proper linker for comparative studies. By chelation of PNA-DTPA and DNA-DTPA conjugates with (111)In(3+) in acidic aqueous solutions, (111)In-labeled PNA and DNA oligomers were obtained. Targeting of single-stranded DNA with PNA-DTPA-[(111)In] conjugates yielded highly localized DNA strand cleavage; the distribution of breaks along the target DNA strand has two maxima corresponding to both termini of PNA oligomer. After 10-14 days, the overall yield of breaks thus generated within the PNA-targeted DNA by (111)In decay was 5-7% versus < or =2% in the case of control oligonucleotide DNA-DTPA-[(111)In]. The estimated yield of DNA strand breaks per nuclear decay is ~0.1 for the PNA-directed delivery of (111)In, which is three times more than for the DNA-directed delivery of this radionuclide. This in vitro study shows that (111)In-labeled PNAs are much more effective than radiolabeled DNA oligonucleotides for site-specific damaging of DNA targets. Accordingly, we believe that PNA oligomers are promising radionuclide delivery tools for future antisense/antigene radiotherapy trials.

Base Sequence↗
PubMed2001

Optimizing radioimmunotherapy by matching dose distribution with tumor structure using 3D reconstructions of serial images.

The biological effect of radioimmunotherapy (RIT) is most commonly assessed in terms of the absorbed radiation dose. In tumor, conventional dosimetry methods assume a uniform radionuclide and calculate a mean dose throughout the tumor. However, the vasculature of solid tumors tends to be highly irregular and the systemic delivery of antibodies is therefore heterogeneous. Tumor-specific antibodies preferentially localize in the viable, radiosensitive parts of the tumor whereas non-specific antibodies can penetrate into the necrosis where the dose is wasted. As a result, the observed biological effect can be very different to the predicted effect from conventional dose estimates. The purpose of this study is to assess the potential for optimizing the biological effect of RIT by matching the dose-distribution with tumor structure through the selection of appropriate antibodies and radionuclides. Storage phosphor plate technology was used to acquire images of the antibody distribution in serial tumor sections. Images of the distributions of a trivalent (TFM), bivalent (A5B7-IgG), monovalent (MFE-23) and a non-specific antibody (MOPC) were obtained. These images were registered with corresponding images showing tumor morphology. Serial images were reconstructed to form 3D maps of the antibody distribution and tumor structure. Convolution of the image of antibody distribution with beta dose point kernals generated dose-rate distributions for 14C, 131I and 90Y. These were statistically compared with the tumor structure. The highest correlation was obtained for the multivalent antibodies combined with 131I, due to specific retention in viable areas of tumor coupled with the fact that much of the dose was deposted locally. With decreasing avidity the correlation also decreased and with the non-specific antibody this correlation was negative, indicating higher concentrations in the necrotic regions. In conclusion, the dose distribution can be optimized in tumor by selecting the appropriate antibodies and radionuclides. This has the potential to lead to a considerable enhancement of the efficacy of RIT in the clinic.

Adenocarcinoma↗