The glycoprotein P-selectin is a cell adhesion molecule of stimulated platelets and endothelial cells, which mediates the interaction of these cells with neutrophils and monocytes. It is a membrane component of cell storage granules, and is a member of the selectin family which includes E-selectin and L-selectin. P-selectin recognizes both lineage-specific carbohydrate ligands on monocytes and neutrophils, including the Lewis x antigen, sialic acid, and a protein component. In inflammation and thrombosis, P-selectin may mediate the interaction of leukocytes with platelets bound in the region of tissue injury and with stimulated endothelium. To evaluate the role of P-selectin in platelet-leukocyte adhesion in vivo, the accumulation of leukocytes within an experimental thrombus was explored in an arteriovenous shunt model in baboons. A Dacron graft implanted within an arteriovenous shunt is thrombogenic, accumulating platelets and fibrin within its lumen. These bound platelets express P-selectin. Here we show that antibody inhibition of leukocyte binding to P-selectin expressed on platelets immobilized on the graft blocks leukocyte accumulation and inhibits the deposition of fibrin within the thrombus. These results indicate that P-selectin is an important adhesion molecule on platelets, mediating platelet-leukocyte binding in vivo, that the presence of leukocytes in thrombi is mediated by P-selectin, and that these leukocytes promote fibrin deposition.

Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets.

This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

https://jnm.snmjournals.org/content/jnumed/40/2/37S.full.pdf

MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

Computed tomography in pulmonary emphysema

Clinical experience with 99mTc-hexamethylpropylene-amineoxime for labelling leucocytes and imaging inflammation.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2009.03498.x

Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø study

Murine monoclonal antibody (Mab) specific for the NH2-terminal region of human fibrin, but not cross-reactive with fibrinogen, was used in radioimmuno-imaging of fresh, induced venous thrombi in three dogs. Iodine-131-labeled Mab was injected intravenously, with iodine 125-labeled polyclonal murine gamma-G globulin (IgG) simultaneously injected as a control. Images were strongly positive at 24 and 48 hours in all three animals, with thrombus-to-blood and thrombus-to-muscle ratios of 8.4 and 228.0, respectively, for I-131-labeled Mab; these ratios for control IgG were 1.2 and 13.0. Radioimmunodetection of thrombi in vivo is feasible in dogs and may have clinical application since Mab is specific to human fibrin.

Radioimmunoimaging of venous thrombi using iodine-131 monoclonal antibody.

Transmission computed tomography (CT), gray-scale ultrasonography, and scinitillation-camera imaging were compared for detection of intrahepatic space-occupying processes. Fifty patients with suspected liver disease were studied by the three modalities. In the 35 cases with confirmed abnormalities, the madalities were rated on a scale of 0 to 5 in terms of their detection value; Each modality was found to have definite advantages and disadvantages. The mean score of ultrasound was highest (3.61), followed by nuclear medicine (3.11) and then CT (2.77). The combination of ultrasound and nuclear medicine identified all lesions, whereas CT alone or in combination with another technique occasionally failed to detect abnormal foci. In the future, the relative efficacy of these procedures may change with improved imaging technology and increased interpreter experience.

Radionuclide imaging, computed tomography, and gray-scale ultrasonography of the liver: a comparative study.

Using rabbit platelets harvested and labeled with either Tc-99m or In-111 oxine as described in Part 1 , we have successfully imaged experimentally induced fresh venous thrombi and newly injured arterial intima. Visualization of lesions up to 6 hr old is striking. Thrombi and arterial damage 24 hr old, however, were usually not imaged successfully; nor were preformed platelet-poor arterial emboli. The varying rates of platelet deposition in vascular lesions of different ages and types account for these observations. Should human cells prove as effective, widespread clinical application is anticipated.

https://jnm.snmjournals.org/content/jnumed/19/5/488.full.pdf

Platelets labeled with oxine complexes of Tc-99m and In-111. Part 2. Localization of experimentally induced vascular lesions.

We have previously reported successful imaging of fresh (2-4 hr old) and aged (1-5 days old) canine thrombi with 131I-labeled intact monoclonal antibody (MAb) specific for fibrin. We now report thrombus imaging with 131I-labeled F(ab')2 and Fab and 111In-labeled intact MAb, F(ab')2, and Fab. Indium-111-labeled F(ab')2 proved to be the best imaging agent due to less nonspecific binding in the liver than whole IgG. Image quality was improved by the higher administered dose permissible with 111In and its better physical characteristics for imaging, compared to 131I. Immunofluorescence of fresh human histologic sections showed intact MAb and F(ab')2 binding to thrombi, pulmonary emboli, and atherosclerotic plaques, strengthening the feasibility of clinical thrombus imaging.

Thrombus imaging with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its F(ab')2 and Fab fragments

The biodistributions of In-111 oxine (with and without leukocyte labeling) of Ga-67 citrate and of In-111 chloride were compared in 30 dogs with chemical and bacterial abscesses and acute joint inflammation. Serial blood samples were taken and tissues radioassayed at 24 hr. The concentration of In-111-oxine leukocytes in all three types of inflammatory lesion was invariably much higher than that of Ga-67 injected simultaneously. For bacterial abscesses, the mean abscess-to-muscle concentration ratio was 3000 for labeled leukocytes and 72 for Ga-67. Aqueous buffered In-111 oxine sulfate solution appeared better for labeling leukocytes than In-111 oxine in ethanol. When In-111 oxine was not incubated with leukocytes before injection, or if the cells were poorly labeled or damaged, the abscess localization was often inferior to that of gallium. Localization of In-111 chloride also appeared inferior to that of gallium. No significant difference in distribution in the major organs or inflammatory lesions was demonstrable between labeled suspensions of pure neutrophils harvested by elutriation and mixed cell suspensions of leukocytes after erythrocyte sedimentation with hydroxyethyl starch. For both types of leukocyte suspension labeled with In-111 oxine, the average recovery of cell-bound activity in the circulating blood at 4 hr was 32% of the administeredmore » activity, inferior to that of DFP-32. It is concluded, therefore, that In-111 oxine is a more effective agent than Ga-67 for the detection of acute focal inflammatory lesions if leukocytes are properly labeled, but current techniques are unsatisfactory for the study of neutrophil kinetics.« less

http://jnm.snmjournals.org/content/21/11/1059.full.pdf

Grossman Zd

Papers

Radioimmunoimaging of venous thrombi using iodine-131 monoclonal antibody.

Radionuclide imaging, computed tomography, and gray-scale ultrasonography of the liver: a comparative study.

Platelets labeled with oxine complexes of Tc-99m and In-111. Part 2. Localization of experimentally induced vascular lesions.

Thrombus imaging with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its F(ab')2 and Fab fragments

Distribution of leukocytes labeled with In-111 oxine in dogs with acute inflammatory lesions.