A predictive test for adverse reactions to contrast media. Preliminary results.

In a prospective study, whole blood samples drawn from patients prior to their being injected with contrast media were incubated with zymosan to activate the complement cascade. The samples were tested for various analytes, including C3a, thromboxane B2 (TxB2), beta thromboglobulin and platelet factor 4 (PF4). Of 207 patients receiving contrast media, only eight experienced reactions, which were mild. Levels of the platelet constituents were generally elevated in these patients. Specificity and sensitivity were 89% and 83%, respectively, for the combined TxB2 and PF4 radioimmunoassay data. Using the Wilcoxon-Mann-Whitney rank sum test, both PF4 and TxB2 were collected with RCM reactions at the R less than .05 level. Although preliminary, the results suggest that RCM reactions are predictable by the in vitro test procedures described.

Radioanalysis of 82Rb generator eluates.

The activity of 82Rb produced from a 82Sr/82Rb generator is dependent on elution conditions (volume and eluent flow rate) and sampling conditions (time and position of collection). Assays for 82Rb in generator eluates are described using a commercial dose calibrator in a static procedure and a plastic scintillator in a dynamic procedure. Dynamic assays more accurately reflect the 82Rb administered when the eluate is injected directly. Radionuclidic contaminants which may be present with 82Sr are identified and procedures for their measurement are described.

Myocardial perfusion with rubidium-82. I. Measurement of extraction fraction and flow with external detectors.

Accurate measurement of the regional extraction of a diffusible radiopharmaceutical is essential for the quantifying of regional blood flow, and may also provide an important physiologic or diagnostic indicator of the cellular viability of an organ in man through external detection by positron emission tomography. However, extraction fraction of a diffusible tracer usually decreases as flow increases, and thus noninvasive methods for measuring flow are nonlinear unless the extraction fraction can be measured independently. This report describes the theoretical basis and documents the applicability of this theory for determining, with external detectors, the first-pass regional extraction fraction of rubidium-82 by the heart, following a single intravenous bolus injection of the tracer. Measurement of extraction fraction was found to be independent of flow, thereby making it possible to determine accurately with a single intravenous bolus injection of rubidium-82, the regional blood flow in the myocardium at up to five times normal resting flow.

A structure-distribution-relationship approach leading to the development of Tc-99m mebrofenin: an improved cholescintigraphic agent.

Thirty-three HIDA (hepatobiliary IDA) derivatives were tested and correlations drawn between physicochemical parameters, structural effects, and in vivo characteristics. Capacity factors of the ligands on reverse-phase HPLC were used as a measure of lipophilicity, and to predict protein binding and in vivo distribution of the complexes. Fragmentary pi values were used to derive theoretical lipophilicities, which showed that ortho substituents have reduced lipophilic activity, probably because of self-shielding. Ortho substitution was found to affect hepatocellular transit times. Various combinations of substituents with the desired overall lipophilicity were tested. The best compound, Tc-3-bromo-2,4,6-trimethyl HIDA, possessed high hepatic specificity, and rapid hepatocellular transit; it was also resistant to competition for hepatobiliary excretion from bilirubin.

Radiopharmaceuticals for hepatobiliary imaging.

Tests for liver function have by and large centered around clinical laboratory diagnostic procedures for a number of years. Besides these, radiographic imaging procedures, including oral cholecystography and intravenous cholangiography, serve a very useful purpose, but several of them are invasive and involve a certain degree of risk from the administered contrast media as well as discomfort to the patient. The cholescintigraphic procedures, though noninvasive, have not played a significant role in the evaluation of hepatobiliary disorders prior to the introduction of the currently available. 99mTc-labeled IDAs. These new hepatobiliary agents offer many advantages over the previously utilized radiopharmaceuticals (131I-rose bengal in particular) in terms of the high degree of specificity for localization in the gallbladder with rapid extraction rates by the polygonal cells of the liver and very low excretion via the GU tract. A detailed understanding of the structure distribution relationship of the various groups in the complex enable the design of agents with an improvement in hepatobiliary specificity and other desirable characteristics. In many clinical situations, even in patients with high bilirubin levels, the 99m-Fc-labeled IDAs offer far superior clinical information over the alternative diagnostic imaging modalities. Further, the absorbed radiation dose imparted to the critical organs is far lower than with the older agents. Thus, the introduction of the cholescintigraphic procedures with the 99mTc-labeled IDAs have ushered in a new phase in the diagnostic workup of patients with impaired hepatocellular function and other biliary disorders.

Membrane transport of Tc-99m-labeled radiopharmaceuticals, I. Brain uptake by passive transport.

The membrane transport properties of twelve Tc-99m complexes were studied by determining each complex's brain uptake index (BUI), extent of protein binding, and octanol-to-saline partition coefficient. The chelating agents used were classified as either N-substituted carbamoylmethyliminodiacetates, substituted oxines, N,N'-diesters of EDTA, or N-substituted derivatives of DTPA. The Tc-99m complexes were found to cross the blood--brain barrier in proportion to their lipophilicity. Of the four types of chelating agents tested, substituted oxines appear to be most suitable for the development of diffusible Tc-99m-labeled compounds for imaging nonexcretory organs.

Evaluation of bowel preparation methods for gallium scanning.

Gallium-67, when injected into the body, is an important diagnostic aid for a variety of diseases. Because it is excreted by the liver into the bowel where accumulation of it can interfere with interpretation of abdominal and pelvic areas, adequate bowel cleansing is necessary. A study comparing three methods of bowel preparation showed the Evac-Q-Kit method to be the most satisfactory and cost effective.

Development of new radiopharmaceuticals based on N-substitution of iminodiacetic acid.

A new approach to radiopharmaceutical design is demonstrated, in which small chelating groups capable of binding gamma-emitting radiometals are attached to biologically active molecules, thus producing radiopharmaceuticals based on bifunctional drug and biochemical analogs. The chelating group iminodiacetic acid has been evaluated for this role by examining two N-substituted iminodiacetic acids: methyliminodiacetic acid (MIDA) and N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (HIDA). Radiochemical and biologic studies showed that both agents were obtained in high radiochemical purity, were stable in vitro and in vivo, and possessed biologic distributions governed almost exclusively by the N-substituted group. These characteristics of 99mTc-labeled N-substituted iminodiacetic acids, prepared using an "instant kit" method, provide the basis for a valuable new class of radiopharmaceuticals based on bifunctional drug and biochemical analogs.

Tissue distribution of technetium-99m and carbon-14 labeled N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid.

The synthesis, radiochemical labeling, and tissue distribution characteristics of N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid are described. The radiopharmaceutical prepared by labeling with 99mTc was rapidly eliminated through the hepato-biliary system of mice. Parent 14C compound was eliminated primarily through the kidney. The 99mTc ion appears to have a greater influence than the organic carrier molecule on the distribution of the radiopharmaceutical.

Early detection of acute rejection in renal allografts using radioiodinated autologous fibrinogen.

131I-labeled autologous fibrinogen was used to detect acute renal allograft rejection in the early postoperative period. Ratios of radioactive counts over transplanted kidneys to those over the heart increased with deposition of radioactive fibrinogen in kidneys undergoing rejection. The test was positive in all instances of acute rejection twelve to twenty-four hours prior to clinical ro biochemical changes. False-positive test results were noted in instances of perinephric hematoma, seroma, and wound abscess and in one patient with urinary tract infection. The test was negative in cases of renal failure secondary to acute tubular necrosis, uric acid nephropathy (in the absence of acute rejection), and chronic rejection. This test is simple, rapid, and practical. It can be performed at the bedside and is free from complications, particularly serum hepatitis.