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The potential of scintigraphy with technetium 99m-labelled J001 (99mTc-J001) to detect synovitis was studied in 15 rabbits with osteoarthritis (OA) of the right knee (section of cruciate ligaments), in five sham-operated rabbits and in four non-operated rabbits. J001 is a non-pyrogenic, acylated poly (1,3) galactoside isolated from the membrane of a non-pathogenic strain of Klebsiella pneumoniae which is able to bind selectively to macrophages via the binding to CD11b and CD14 molecules. The results of 99mTc-J001 scintigraphy were compared with those of scintigraphy with 99mTc-labelled methylene diphosphonate (99mTc-MDP) and GC-APG (a derivative of J001 unable to bind macrophages in vitro). The mean scintigraphic ratios (diseased healthy knee) of 99mTc-J001 were significantly higher in OA rabbits than in sham- and non-operated rabbits, from as early as day 18 until day 90. 99mTc-J001 scintigraphy demonstrated earlier increased uptake than 99mTc-MDP scintigraphy. The mean scintigraphic ratios of 99mTc-J001 were significantly higher than those of 99mTc-GC-APG (which remained normal) in OA rabbits. The normal scintigraphic ratios of 99mTc-J001 in sham-operated and non-operated rabbits, as well as of 99mTc-GC-APG in OA rabbits, suggested that the increased uptake demonstrated with 99mTc-J001 in OA rabbits, as early as day 18 corresponded to imaging of synovitis via elective macrophage targeting. These results showed that 99mTc-J001 scintigraphy should be a specific method of detecting synovitis in OA.

Background and Objective: J001 scintigraphy is a new approach, based on macrophage targeting, developed for tumor and inflammation imaging. J001, a non-pyrogenic acylated poly(1,3)galactoside purified from the membrane of a non-encapsulated strain of Klebsiella pneumoniae associates selectively with macrophages via binding to CD11b and CD14 molecules. Since macrophages play a primary role in inflammatory arthritis processes, J001 labeled with 99mTc appeared to be of interest for the scintigraphic imaging of inflammatory lesions. The purpose of this study was to assess the potential of J001 scintigraphy for imaging inflammatory arthritis in the model of ovalbumin-induced arthritis in rabbits., Material and Methods: Ovalbumin-induced arthritis was developed in 17 rabbits. 99mTc-J001 scintigraphy was performed 4 weeks after arthritis induction in 17 rabbits and was repeated at 6 and 8 weeks in 8 rabbits. 99mTc-J001 and 99mTc-MDP scintigraphy were performed before and 2.5 months after radionuclide synovectomy with the intra-articular injection of a high energy beta-emitting radionuclide (186Re) in 3 rabbits and 186Re (first subjected to a complete decrease of radioactivity) in 3 rabbits., Results: 99mTc-J001 scintigraphy was able to image inflammatory arthritis 4 weeks after induction. J001 scintigraphy demonstrated an increased uptake earlier than MDP, which was maintained at week 8. After radionuclide synovectomy, a clear decrease in the J001 scintigraphy ratio occurred, whereas the MDP scintigraphy ratio was stable. After the intra-articular injection of inactive 186Re, no changes in MDP and J001 scintigraphy ratio appeared., Conclusion: 99mTc-J001 scintigraphy is able to image joint inflammation and to assess the response to anti-inflammatory treatment in an experimental model of arthritis.

Macrophagal function of the liver and the spleen has been studied using dynamic scintigraphy in 46 patients with chronic lymphatic and myeloid leukemia. There was an increase in the share of the spleen in total accumulation of radionuclide, shortening of the time of its capture by the liver macrophages and an increase in the indices of hepatic and splenic clearance with the same total time of drug elimination from the blood. The above changes became more distinct with leukemia progression and seem to be more severe in chronic myeloid leukemia.

The potential of 99m-Tc-J001 for the investigation of inflammatory lesions via the targeting of recruited macrophages (M phi) has already been documented in several experimental models and in human diseases. To achieve a functional imaging of inflammation via M phi targeting, minimal labeled colloid content and high in vivo stability of 99mTc-J001 are essential. The actual specificity of such scintigraphy is closely dependent upon the radiolabeling of only the J001 molecules available for M phi targeting. To develop an appropriate radiopharmaceutical kit, optimization of the labeling conditions was achieved from a series of pilot formulations that were evaluated for radiolabeling efficiency and both in vitro and in vivo 99mTc-J001 stability. Colloids were characterized using autocorrelation spectroscopy and multiangle laser-light scattering, radioactive colloid content of the formulations being deduced from biodistribution studies. This work has made possible the definition of a formulation exhibiting a radiolabeling yield > 97.0%, associated with in vivo stability and minimal colloid formation, thus greatly enhancing the specificity of such macrophage scintigraphy.

Interleukin-1 beta (IL-1 beta) is known to have a number of effects on the different cell types present within coronary arteries. In this study we identified the location and phenotype of cells containing IL-1 beta in human coronary artery specimens from patients suffering from either coronary atherosclerosis or cardiomyopathy and correlated the presence of IL-1 beta with disease severity. Luminal endothelial cells, adventitial vessel wall cells, and macrophages were double labeled immunohistochemically for IL-1 beta protein and a cell type-specific monoclonal antibody for either endothelial cells or macrophages. In situ hybridization was performed to locate the presence of IL-1 beta mRNA within the coronary artery wall. In this study IL-1 beta protein was found to be increased in the adventitial vessel walls of atherosclerotic coronary arteries compared with coronary arteries from nonischemic cardiomyopathic hearts. This increase was directly proportional to the severity of coronary atherosclerosis. IL-1 beta protein was also detected in luminal endothelium and macrophages of atherosclerotic coronary arteries and coronary arteries from nonischemic cardiomyopathic hearts. IL-1 beta mRNA was found in luminal endothelial cells, adventitial vessel endothelial cells, and macrophages. We conclude that IL-1 beta is produced by endothelial cells and macrophages in coronary arteries from ischemic hearts and to a lesser extent from nonischemic cardiomyopathic hearts.

Lymphoscintigraphy usually involves labeled microparticles or colloids that distribute in the lymph flow. A new strategy for imaging pathological lymph nodes would be the targeting of macrophages recruited in these lesions. The potential for lymphoscintigraphy of the highly diffusible J001X acylated polygalactoside labeled with 99mTc was studied and compared to usual colloidal agents in a model of infectious granulomas developed in sheep. Scintigraphic and histological assessment of the specificity of targeting was performed using a MAb (OM1) raised against ovine macrophages taken as reference. This study has evidenced the ability of J001X specifically to image pathologic lymph nodes and more especially the second lymph node in the same chain with a significant scintigraphic contrast.

Unlabelled: A substantial amount of macrophage infiltration occurs in both human and animal tumors. We previously showed that 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake was higher in tumor-associated macrophages and young granulation tissues than in tumor cells. Differentiation of intratumoral non-neoplastic cells from neoplastic cells is important not only for the reduction of false-positives in FDG-PET tumor studies but also for patient management., Methods: A time-course study was performed using micro- and macro-autoradiography and tissue distribution in C3H/He mice bearing transplanted syngeneic FM3A mammary carcinoma and MH134 hepatoma was evaluated to analyze the intratumoral cellular dynamics of [18F]FDG and 2-deoxy-D-[3H]glucose in vivo., Results: The volume-doubling time in vivo was 1.3 days for MH134 and 4.9 days for FM3A, and the survival time of the host was 32.1 and 40.3 days, respectively. The peak uptake of both tracers in the tumor was 60 min after intravenous injection. The uptake by MH134 was 1.7-2.1 times higher than that by FM3A. The intracellular concentration as determined by counting the silver grains on micro-autoradiographic sections showed that the uptake by macrophages and focal small necrotic areas in both tumors was faster than the blood clearance until 15 min after tracer injection., Conclusion: Thus, non-neoplastic cellular elements can be differentiated from viable neoplastic cells by means of the dynamic analysis of [18F]FDG uptake.

Although several approaches already exist for the imaging of inflammatory foci, new specific strategies providing functional data on the lesions are required to determine the extent of the disease and also to assess anti-inflammatory treatment. In our study, we investigated the scintigraphic potential of 99mTc-J001X, an agent developed for the targeting of macrophages. Due to its well documented and progressive evolution of lesions, a model of radiation-induced inflammation in pigs was chosen. Our results demonstrated the ability of J001X to provide images of inflammatory foci with a high contrast. The contribution of some specific and non-specific parameters possibly involved in the scintigraphic behavior of J001X is discussed.

Murine peritoneal macrophages insonated in vitro at 37 degrees C were assayed for impairment of adhesion to and spreading on glass coverslips, expressions of Fc gamma and C3b receptors, and phagocytosis. Insonation conditions were typical for exposures by B-mode imaging equipment and approximated the most severe exposures anticipated in use of pulsed Doppler equipment. In no case were the assay results for insonated samples significantly different from those for the sham-exposed controls.

The scintigraphy of the bone marrow can supply information for its distribution in the body and for its functional state as well. The purpose of the study is to assess the efficacy of the scintigraphic imaging of the bone marrow by means of radiopharmaceutical drugs--99mTc-sulfur colloid for imaging the monocytic macrophagal system and 111In-chloride for imaging of erythroid cells--and to determine its characteristics in some hematologic diseases. 72 patients with hematologic diseases and 10 healthy controls were examined. The results lead to the conclusion that bone marrow scintigraphy is a useful method which helps the physician in the diagnosis of hematologic diseases, the determination of the stage of the disease, the assessment of the efficacy of the treatment applied and in all cases of discrepancy between the bone marrow histology and the clinical status of the patient.