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Effect of pH on the formation of Tc(NaBH4)-MDP radiopharmaceutical analogues.

Anion exchange high performance liquid chromatography has been employed to separate components of 99mTc(NaBH4)-MDP formulations prepared as a function of pH, the presence or absence of 99Tc carrier, and the presence or absence of air. The formulation pH is an effective variable for controlling the generation and interconversion of 99mTc-MDP components, and for allowing the preparation of large quantities of specific 99mTc-MDP complexes for biological evaluation.

Air↗

Alternative positron emission tomography with non-conventional positron emitters: effects of their physical properties on image quality and potential clinical applications.

The increasing amount of clinically relevant information obtained by positron emission tomography (PET), primarily with fluorine-18 labelled 2-deoxy-2-fluoro-D-glucose, has generated a demand for new routes for the widespread and cost-efficient use of positron-emitting radiopharmaceuticals. New dual-head single-photon emission tomography (SPET) cameras are being developed which offer coincidence detection with camera heads lacking a collimator or SPET imaging with specially designed collimators and additional photon shielding. Thus, not only satellite PET imaging units but also nuclear medicine units investing in these new SPET/PET systems need to examine all available alternatives for rational radionuclide supplies from host cyclotrons. This article examines 25 "alternative" positron-emitting radionuclides, discusses the impact of their decay properties on image quality and reviews methods for their production as well as for their application in imaging techniques.

Humans↗

Kr-81m calibration factor for the npl ionisation chamber.

A general method has been developed for the measurement of the activity concentration of 81mKr gas. Due to its short half-life, 13.1s, this gas has to be eluted from a 81Rb/81mKr generator. The 81Rb parent has a half-life of about 4.6 h. The calibration was done in two steps: firstly, a gamma-ray spectrometer was calibrated using 51Cr and 139Ce sources, nuclides with gamma-ray energies bracketing that of 81mKr (190.5 keV). The measurement geometry was equivalent to that of the 81mKr measurement; the sources were inserted into two collimated PTFE tubes in front of the gamma-ray detector. Secondly, a calibration factor for the NPL radionuclide calibrator was determined with a specially designed ionisation chamber insert. The 81mKr gas passed in front of the gamma-ray detector in PTFE tubing before and after entering the ionisation chamber. The calibration factor for 81mKr in the radionuclide calibrator with this geometry was independent of the gas flow rate within determined limits. The analytical calculations of the activity determination, uncertainties and measurement criteria are discussed.

Algorithms↗

Immunologic, morphologic, and functional evaluation of long-term-surviving beagle lung allograft recipients treated with lethal total-body irradiation, autologous bone marrow, and methotrexate.

Immunologic, morphologic, and functional evaluations were performed in beagle dogs with single lung allografts surviving 3-13 years after transplantation. Immunosuppressive treatment included lethal total-body irradiation, autologous bone marrow reconstitution, and three doses of methotrexate. Three beagle recipients with full DLA-haplotype-matched grafts and five recipients with one-haplotype-mismatched grafts were studied. Evidence of rejection--i.e., infiltrates on chest roentgenograms, hypoperfusion on radionuclide lung scans, and histopathologic changes--were absent in the matched recipients and in three of the five mismatched recipients. Two of the mismatched recipients had decreased perfusion to their allografted lungs, and open-lung biopsy specimens revealed diffuse fibrotic blood vessels with narrowed lumina but no other abnormalities. Decreased fractional blood flow to the lung allograft of the five one-haplotype-mismatched recipients was correlated (r = -0.92) with the level of donor-specific cytolytic lymphocyte activity generated in mixed lymphocyte cultures (MLC). In contrast, the level of proliferative activity in donor-specific MLC did not correlate well with graft function. These findings suggest that the mechanism of tolerance to these lung allografts (with particular regard to vascular integrity) involves attenuation of the response against major histocompatibility complex (MHC) class I alloantigen since the induction of cytolytic T lymphocytes in MLC is directed primarily against these molecules. Though all of the mismatched recipients had the ability to react against MHC class II alloantigens in vitro (as demonstrated by proliferative responses in MLC), in vivo responses to class II gene products may not occur because of the lack of expression of these molecules on long-term surviving grafts.

Animals↗

Tumor markers in gynecologic cancer.

The development of biochemical tumor markers has increased the use of antibody-dependent tumor marker assays in gynecologic oncology. Several monoclonal antibodies directed against novel epitopes on tumor-associated antigens have allowed the development of sensitive assays for serum markers. Assays for human chorionic gonadotrophin and TA-4 have been improved. CA 125 has provided a useful first-generation markers. Ovarian cystoadenocarcinoma-associated antigen and lipid-associated sialic acid have been developed for ovarian cancer, transforming growth factor for squamous cancer, and placenta protein 4 for endometrial and cervical cancer. The most widely applied procedures to identify these markers are immunofluorescent microscopy and immunocytochemical staining. Multiple markers and modalities may be required to increase the sensitivity of tumor detection. CA 15-3 and GCDFP-15 markers have been useful in detecting breast cancer. The application of radionuclide imaging will provide a new field for the diagnosis of gynecologic malignancies.

Biomarkers, Tumor↗

18FDG PET scanning of benign and malignant musculoskeletal lesions.

OBJECTIVE: To describe the technique, applications and advantages of (18)FDG PET scanning in detection, analysis and management of musculoskeletal lesions. DESIGN AND PATIENTS: Forty-five patients (19 males,26 females) aged 9 to 81 years had radiographs, routine radionuclide scans, CT and/or MRI of clinically suspected active benign or malignant musculoskeletal lesions. (18)FDG scans with a Siemens ECAT EXACT 921 dedicated PET unit (Knoxville, Tenn.) and FWH=6 mm images acquired as a 5-6 bed examination (6 min emission and 4 min transmission) used OSEM iterative reconstruction with segmented transmission attenuation correction and a Gaussian filter (cutoff 6.7 mm). Region of interest (ROI) 3x3 pixel image analysis based on transverse whole body images (slice thickness 3.37 mm) generated Maximum Standard Uptake Values (Max SUV) with a cutoff of 2.0 used to distinguish benign and malignant lesions. RESULTS: Thirty-nine studies were available for SUV ROI analysis. Overall sensitivity for differentiating malignant from benign osseous and non-osseous lesions was 91.7% (22/24), overall specificity was 100% (11/11) with an accuracy of 91.7%. All aggressive lesions had a Max SUV >2.0. Data separating benign from malignant lesions and aggressive from benign lesions were statistically significant ( P<0.001) in both categories. There was no statistically significant difference in distinguishing aggressive from malignant lesions ( P, ns). CONCLUSION: (18)FDG PET contributes unique information regarding metabolism of musculoskeletal lesions. By supplying a physiologic basis for more informed treatment and management, it influences prognosis and survival. Moreover, since residual, recurrent or metastatic tumors can be simultaneously documented on a single whole body scan, PET may theoretically prove to be cost-effective.

Adolescent↗

A report generator package for routine laboratory tests in a hospital cardiology department.

A simple report generating package is described. The package is designed for hospital computing personnel who wish to develop fast, easy access, easy-to-use report generating programs for use by non-computer specialists. Use of the system is illustrated by examples from three sections within a hospital cardiology department: nuclear cardiology, M-mode echocardiography and reporting of 24-hour ambulatory electrocardiogram tapes.

Cardiology↗

Salivary scan after major ablative head and neck surgery with prediction of postoperative fistulization.

Patients with carcinoma of the head and neck undergoing major ablative and reconstructive procedures following periods of prolonged debilitation, chemotherapy, and/or radiation therapy have been identified as having a high risk for postoperative wound complication, most often infection. Does postoperative wound infection arise de novo, does infection result from failure of prophylactic antibiotic coverage, or is it the result of anastomatic salivary leak? To investigate the incidence of unrecognized salivary leak into the neck, 24 patients underwent salivary radioisotope studies using technetium 99m sodium pertechnetate from three to six days postoperatively. The isotope was administered early in the morning with drainage bags empty. Patients and the collection system were scanned for activity between four and six hours later. Nine patients had postoperative evidence of salivary secretion radioactivity in their drainage system. All of these patients developed transient wound infections or fistulas. The remaining 15 had no uptake in their collection systems and no wound complications. We suggest that the preliminary results from this noninvasive, simply administered study indicate that the infected surgical neck wound may be secondary to unrecognized postoperative salivary contamination. This technique can be used to provide early identification of potential wound infection. Alternatively, information generated by this kind of study may be valuable in predicting patients with the highest risk for postoperative infection, thereby offering guidelines for the use of perioperative antibiotic prophylaxis.

Head and Neck Neoplasms↗

Stress fracture of the ribs in female rowers.

Stress fractures of the lower ribs related to sports are rare. Fractures of the ribs related to rowing sports have not been reported. We have documented seven cases of stress fractures of the lower ribs in female athletes; four were elite rowers and three were engaged in tennis, golf, and gymnastics. Each athlete was initially seen and treated elsewhere for muscular strain. All athletes presented with pain in the posterolateral thorax in and around the scapula. The time from onset of symptoms to diagnosis ranged from 2 to 6 months. Bone scans were used to document the fractures when roentgenograms were equivocal. Each athlete responded to a 4 to 8 week period of rest or training modification. Biomechanical analysis of the forces across the ribs demonstrates that these fractures tend to occur along the posterolateral segment where the bending stresses on the rib are greatest. The predominant muscle forces are generated by the forced couple of scapular retraction and protraction acting through the serratus anterior. We postulate that inadequate strength and resistance training background in women is the cause for the apparent increased susceptibility of women to these skeletal injuries.

Adult↗

[Direct integral linear least square regression method for kinetic evaluation of hepatobiliary scintigraphy: clinical application and evaluation of 170 hepatograms].

Kinetic evaluation of 170 hepatobiliary scintigrams was performed using direct integral linear least square regression method (DILS method). Liver time-activity curve (TAC) data were fitted to 2 types of 1 compartment model using heart TAC as input function. One model was 1 compartment model with 2 parameters (extraction rate (ku) and excretion rate (ke)), the other had another parameter for representing non-specific volume of distribution (Vn) in liver. Obtained parameter estimate was then examined to see how they correlate with three major visual findings of scintigram; low tracer uptake, intrahepatic cholestasis, extrahepatic cholestasis. In both models, ku showed significant difference between low uptake positive and negative groups and ke showed significant difference between extrahepatic cholestasis positive and negative groups. Only mean uptake time (Vn/ku) by 3 parameter model showed significant difference between intrahepatic cholestasis positive and negative groups, although the other 2 parameters (ku, ke) were insensitive to intrahepatic cholestasis in either model. Thus, the 3 parameter model was superior to the 2 parameter model because of its sensitivity to intrahepatic cholestasis and ability to differentiate extrahepatic and intrahepatic cholestasis as the difference of parameter values. Based on this 3 parameter model, parametric images were generated by calculating parameter value of each pixel using the DILS method. The DILS method could determine parameters by simple calculation, and hence was very powerful in processing parametric images, which processing otherwise required immense calculation.

Biliary Tract↗

[Characteristics of radiopharmaceutical delivered from 99mTc-DTPA in the technegas generator].

99mTc-DTPA aerosol permeates the alveolar membrane by an intercellular pathway. Measurement of the clearance rate of 99mTc-DTPA aerosol is useful for assessing injury of the lung epithelium. Pertechnegas (P-gas) is also used to assess epithelial permeability, but its clearance is too rapid to evaluate lung epithelial permeability. The aims of this study were first to generate 99mTc-DTPA fine aerosol (D-gas), second to characterize D-gas by radiochromatography and an in vivo study in the rat, and third to investigate the clinical significance of D-gas in comparison with 99mTc-DTPA aerosol and P-gas. We generated D-gas in a chamber with an atmosphere of 3% oxygen and 97% argon inside the Technegas Generator. The clearance half-time of D-gas was 19.8 +/- 4.0 min in eight normal non-smoker subjects, 12.0 +/- 2.8 min in four smoker subjects, and 31 +/- 11.2 min in three with idiopathic interstitial pneumonia (IIP). In radiochromatography, the development of D-gas was the same as that of P-gas and different from that of 99mTc-DTPA solution. In the in vivo study using a rat, the distribution of intravenously injected D-gas solution was the same as that of 99mTcO4-, but different from that of 99mTc-DTPA solution. These results suggest that 99mTc-DTPA separates to free 99mTcO4- in the chamber of the Technegas Generator and that D-gas behaves in the same manner as P-gas. In conclusion, D-gas has no clinical significance for the assessment of epithelial permeability.

Aerosols↗

RADIONUCLIDE COMPUTED TOMOGRAPHY: APPLICATIONS IN CARDIOVASCULAR DISEASE.

Tomography is an imaging modality in which information in one plane is displayed in focus while information from overlying and underlying planes is either blurred or eliminated. As a result, there is an improvement in the contrast of structures in the plane of interest. Computerized axial tomography (CAT) is an imaging modality in which a digital computer mathematically reconstructs the image of a plane or section from data collected perpendicular to the axis of that plane. The axis of the plane and the patient's long axis usually coincide so that the reconstructed images reveal transverse sections. In recent years, two types of computed tomography in medical imaging have generated a great deal of interest. These are X-ray transmission and radio-nuclide emission computed tomography.

Journal Article↗

A novel 125I-labeled daunorubicin derivative for radionuclide-based cancer therapy.

INTRODUCTION: Auger electron emitters, such as (125)I, are getting increasingly wider recognition as alternatives to current anticancer treatments. The effectiveness of Auger electrons is strongly dependent on their proximity to DNA and is therefore considered as harmless outside the nucleus. METHODS: (125)I or (127)I was conjugated with Comp1, Comp2 or Comp3 - three derivatives of the chemotherapeutic drug daunorubicin. Their capacity factors, DNA-binding constants and exclusion parameters, and the degree of DNA fragmentation after incubating isolated DNA with our (127)I- or (125)I-conjugated daunorubicin derivatives were determined. Human breast adenocarcinoma (SK-BR-3) cells were incubated with the derivatives; fluorescent microscopy and autoradiography images were generated; and cell growth was monitored. RESULTS AND DISCUSSION: The capacity factor of (127)I-Comp1 was similar to those of daunorubicin and doxorubicin, whereas lower capacity factors of (127)I-Comp2 and (127)I-Comp3 suggested reduced interactions with lipid membranes. DNA exclusion parameters and binding constants of (127)I-Comp1 and (127)I-Comp2, but not of (127)I-Comp3, were similar to those of doxorubicin. Fluorescent microscopy and autoradiography images of SK-BR-3 cells revealed that (127)I-Comp1 and (125)I-Comp1 accumulated in tumor cell nuclei, whereas (127)I-Comp2 and (127)I-Comp3 were present predominantly in other cell compartments. The binding of (125)I-Comp1 to isolated chromosomal DNA led to major fragmentation. Incubation of SK-BR-3 cells with (125)I-Comp1 inhibited cell growth, whereas doxorubicin or (127)I-Comp1 administered at the same concentration had no effect on cell growth. Our results thus suggest that (125)I-Comp1 has the potential to become a new tool for anticancer therapy.

Cell Line, Tumor↗

The AAPM/RSNA physics tutorial for residents. Introduction to emission CT.

The article explores the fundamentals of emission computed tomography (CT) from a nonmathematical approach. Tomographic images reveal the internal distributions of radioactivity in three-dimensional objects, and thus allows anatomic localization and improves contrast. Tomography requires a stable distribution of radionuclides, uniform detector response, an accurate center of rotation, and a complete set of projections. In emission CT, a large number of measurements, called projections, are collected at various angles about the patient during the examination. This information is organized by the angles of acquisition into a stack, called a sinogram. Each projection is modified by applying a reconstruction filter (eg, ramp or windowed reconstruction filters). These modified projections are backprojected to form the transverse tomographic images. The quality of tomographic images generated from filtered backprojection depends on the underlying assumptions about the projections. Typical artifacts that result from violations of these assumptions include motion, uniformity, and attenuation artifacts. In addition, an inaccurate center of rotation, insufficient angular sampling, and errors in selection of pixel size can result in poor-quality reconstructed images.

Artifacts↗

Synthesis and evaluation of a bromine-76-labeled PPARgamma antagonist 2-bromo-5-nitro-N-phenylbenzamide.

Peroxisome proliferator activated-receptor gamma (PPARgamma) binds to peroxisome receptor response elements with its heterodimeric partner, retinoid X receptor, and regulates downstream gene expression. PPARgamma transcriptionally modulates fat metabolism, and receptor agonists have been developed to treat type II diabetes. PPARgamma is also overexpressed in some tumor cell lines and primary tumors, including breast and prostate tumors. Two PPARgamma antagonists, 2-chloro-5-nitro-N-phenylbenzamide (GW9662) and 2-chloro-5-nitro-N-pyridin-4-yl-benzamide (T0070907), represent good lead compounds for radiotracer development. In the current study, four additional halogen substituted analogs were synthesized and evaluated in a whole cell screening assay for PPARgamma binding activity. Two bromine-containing analogs having EC50 values <5 nM were chosen for bromine-76 radiolabeling. Bromine-76-labeled 2-bromo-5-nitro-N-phenyl-benzamide was selected for subsequent in vitro and in vivo studies due to its superior radiolabeling yield (approximately 70%) and the well-characterized pharmacological properties of its analog GW9662. An in vitro stability study showed that 40% of the compound remained intact in plasma and about 25% in whole blood after 30 min. Biodistribution studies in MDA-MB-435 human breast tumor-bearing nude mice were carried out at 5 min, 30 min, 2 h and 24 h post injection of the radiotracer. Although in vivo metabolite studies demonstrated rapid compound degradation, at least 10% of the parent compound was delivered to the tumor. We are currently exploring second generation analogs of these lead compounds for the development of radiolabeled antagonists of the PPARgamma receptor.

Anilides↗

Supernormal vision, high-resolution retinal imaging, multiphoton imaging and nanosurgery of the cornea--a review.

Wavelength-corrected, adaptive optics and their relevance for diagnostic procedures of the human retina are considered. First, it is shown that the compensation of errors of the dioptric apparatus of the eye allows sharp and high-contrast images of retinal elements, such as the photoreceptors, to be generated. This technology is expected to enable on the one hand an improved laser therapy by the application of laser spots of the size of single receptors as well as on the other a further understanding of the mechanisms of vision, in particular of colour vision by using colour stimuli not larger than the cones. Second, femtosecond laser pulses, emitted from lasers working in the near infrared, based on multiphoton effects allow both imaging and laser effects to be generated which are in the submicron range and which do not cause collateral damage (nanoimaging and nanosurgery). These procedures, related to experimental ophthalmology may be considered a milestone for the research of cell physiology, in particular in the subcellular range.

Biomedical Technology↗

A versatile computer simulation of the left ventricle.

A versatile mathematical simulation of a beating left ventricle, as seen in a gated cardiac blood-pool study, is described. The basic model consists of a fifth-degree polynomial rotated about its long axis. Motion is mimicked by sinusoidally varying the lengths of the long and short axes. The quality of clinical images is simulated through addition of Poisson noise and camera blur, determined from the measured line-spread function for Tc-99m. To achieve added realism, the modeled ventricle can be inserted in place of the patient's actual ventricle in clinical images. The dimensions, activity, and ejection fraction can all be adjusted. In addition, regional wall-motion abnormalities can be generated in any of the walls. To illustrate applications of the model in testing and evaluating cardiac computer programs, the performances of two ejection-fraction programs are compared, and use of the model in evaluating digital filtering algorithms is discussed.

Computers↗

Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature.

Investigation of the kindred of a 58-year-old woman with all of the features of "adult" hypophosphatasia revealed 12 individuals in 3 generations with subnormal circulating total alkaline phosphatase (AP) activity. The pattern of inheritance suggested autosomal dominant transmission, with incomplete penetrance of the trait particularly in the young males. Hypophosphatasic individuals other than the proposita were clinically well but had loss of permanent teeth, showing that dental abnormalities could be the only clinical manifestation of the disorder. Radiographic investigation of the proposita revealed that completion of stress fractures was necessary for healing; maturation of incomplete fractures resulted in stable Looser zones. Skeletal survey and radionuclide bone imaging were unremarkable in hypophosphatasic individuals without fracture. Subclinical osteopenia was found in several affected women by metacarpal cortical width and bone densitometric measurements. Laboratory studies showed increased plasma and urinary phosphoethanolamine levels in affected individuals. Phosphoethanolamine and phosphoserine appeared to be natural subtrates for AP since a negative correlation existed between each substrate and circulating total AP activity. Phosphoethanolamine and phosphoserine levels were greatest in the clinically affected proposita; furthermore, only she showed absence of leukocyte AP activity. Heat fractionation of her total circulating AP activity suggested severe reduction in the bone isoenzyme. Hypophosphatasic children had higher levels of total circulating AP than affected adults; the increase was apparently secondary to increased bone isoenzyme. Iliac crest bone biopsies showed greater abnormality in affected women. Osteoidosis was particularly pronounced in the proposita's younger affected sister and hypophosphatasic daughter. Histomorphometric analyses of the biopsies revealed a paucity of osteoblasts despite increased quantities of unmineralized matrix. The finding that hypophosphatasic children in this kindred had higher circulating total AP activity than adults and were able to model their skeleton normally, together with observations that the bone biopsy in adults had a paucity of osteoblasts, suggests that some factor(s) during growth is able to induce both AP activity and osteoblast function, or, that this disorder is an "abiotrophy" with deficient osteoblastic formation and/or accelerated destruction in adult life.

Adolescent↗