technetium-tc-99m-exametazime and Arthritis--Rheumatoid

The aim of this study was to test the applicability of 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leukocyte joint scintigraphy in the assessment of disease activity in 21 patients with rheumatoid arthritis, and to compare leukocyte scintigraphy with the Disease Activity Score (DAS), a validated activity index developed by the European League Against Rheumatism (EULAR). Twenty-one patients with rheumatoid arthritis were investigated by using 99mTc-HMPAO labelled leukocyte joint scintigraphy. The clinical and laboratory data were recorded, and the DAS was calculated and compared with the scintigraphic results in each case. A relatively high DAS score (4.71+/-1.07) was found in the majority of patients. The degree of accumulation of 99mTc-HMPAO leukocytes showed no correlation with a patient's age, gender, duration of disease, use of disease modifying anti-rheumatic drugs (DMARDs), visual analogue scale (VAS), Richie index, DAS, or any laboratory parameters. In contrast, a significant correlation was found between the global regional accumulation of the labelled leukocytes of the hands and feet, and the swollen-joint count. It is concluded that radiolabelled leukocyte scintigraphy could become one of the promising methods in the assessment of disease activity in patients with rheumatoid arthritis.

Topics: Adult; Arthritis, Rheumatoid; Female; Foot; Hand; Humans; Leukocytes; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime

Rheumatoid arthritis (RA) involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration could be portrayed scintigraphically to monitor noninvasively the effects of therapy on the progress of the disease. For this purpose, labeling of purified autologous monocytes with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) at very high specific radioactivity has recently been developed. The aim of this study was to assess the biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in adult patients with RA.. In 8 patients with RA, monocytes were isolated from 100 mL of blood and labeled with 99mTc-HMPAO to a yield of 10 Bq/cell. Multiple whole-body scans were performed up to 20 h after reinjection of an average of 200 MBq of 99mTc-HMPAO-labeled monocytes. Urine and blood samples were collected. The fraction of administered activity in 7 source organs was quantified from the attenuation-corrected geometric mean counts in conjugate views. Radiation-absorbed doses were estimated with OLINDA/EXM software.. Autologous monocytes labeled with 99mTc-HMPAO at high intracellular yields showed in vivo kinetics comparable with labeled leukocytes, with initial trapping in the lungs followed by distribution into the liver, spleen, and bone marrow. The radiation-absorbed estimates for 99mTc-HMPAO-labeled monocytes were comparable with those for 99mTc-HMPAO-labeled mixed white blood cells, with an effective dose of 0.011 mSv/MBq.. 99mTc-HMPAO-labeled monocytes have biodistribution and radiation dosimetry similar to those of 99mTc-HMPAO-labeled mixed white blood cells and might therefore be used for in vivo monitoring of immunomodulating therapy in patients with RA.

Topics: Adult; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Monocytes; Radiometry; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tissue Distribution; Whole Body Imaging

Rheumatoid arthritis of joints involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration can be portrayed scintigraphically in order to monitor noninvasive effects of therapy on the progress of the disease. Scintigraphic detection of inflammation by means of technetium 99m-hexamethylpropylene amine oxime (99mTc-HMPAO)-labeled leukocytes provides a classic example. Present state-of-the-art methods in cell biology allow the isolation of cells like lymphocytes or monocytes, which are less abundant than main blood constituents but, instead, harbor particular functions like specific homing properties. To facilitate scintigraphic imaging of the cell functions involved, the relatively small population of cells must be labeled to radioactive yields as high as possible. We demonstrate that autologous monocytes isolated from 100 ml of peripheral blood can be radiolabeled to a yield of 10 (instead of 1) Bq per cell, allowing scintigraphic analysis of rheumatoid arthritis up to 20 h post injection of patients. The method is based on the instantaneous distribution of lipophilic 99mTc-HMPAO between the hydrophobic inside of cells and the hydrophilic (aqueous) surrounding of cells, followed by decomposition of the radiopharmaceutical into compounds that are unable to cross the cellular membrane. The procedure provides a method of choice for cell-mediated scintigraphy at low availability of cells with the correct homing properties.

Topics: Arthritis, Rheumatoid; Cells, Cultured; Humans; Isotope Labeling; Monocytes; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime

To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP).. Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium-99 hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled from indium-111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time.. Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on the modified Health Assessment Questionnaire (P<0.05), tender joints (P<0.005), VAS for pain (p<0.005), and generalized stiffness (P<0.005), as well as a decrease in the C-reactive protein level (P<0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis.. Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.

Topics: Aged; Arthritis, Rheumatoid; Cell Movement; Female; Humans; Joints; Male; Methylprednisolone; Middle Aged; Neutrophils; Organometallic Compounds; Organotechnetium Compounds; Oximes; Oxyquinoline; Radionuclide Imaging; Technetium Tc 99m Exametazime

To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA).. After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection.. An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours.. The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis.

Topics: Aged; Arthritis, Rheumatoid; Cell Movement; Female; Humans; Kinetics; Lymphocytes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Synovial Membrane; Synovitis; Technetium Tc 99m Exametazime; Time Factors

Topics: Arthritis, Rheumatoid; Humans; Leukocytes; Lymphadenitis; Male; Middle Aged; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Synovitis; Technetium Tc 99m Exametazime

A comparative study of neutrophil pharmacokinetics and distribution between normal volunteers and patients with rheumatoid arthritis (RA) is presented. White cell viability was confirmed by prominent localization of activity in the spleen with minimal liver uptake and lack of retention in the lungs in both normal volunteers and RA patients. There were no significant differences between both groups in granulocyte clearance from the lungs and their subsequent distribution in the spleen, bone marrow and liver. The results of this study demonstrate that the behaviour of granulocytes in RA patients is essentially unchanged from that of normal volunteers.

Topics: Aged; Arthritis, Rheumatoid; Cell Survival; Female; Humans; Male; Middle Aged; Neutrophils; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Reference Values; Technetium Tc 99m Exametazime

The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime-labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA.

Topics: Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cell Movement; Female; Humans; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Neutrophils; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime; Technetium Tc 99m Medronate; Triamcinolone Acetonide

Technetium-99m-labelled, non-specific, polyclonal, human immunoglobulin G (99mTc-hIG) has been used to quantify synovial inflammation in rheumatoid arthritis. A comparison was carried out between the scintigraphic results obtained with this tracer, 99mTc-hexamethylpropylene amine oxime-labelled white blood cells (99mTc-WBC) and 99mTc-albumin nanocolloids (99mTc-NC). Twenty patients affected by rheumatoid arthritis and suffering from clinically active synovitis were studied with 99mTc-hIG. The number and sites of the involved joints had been previously assessed on the basis of the presence of pain and/or swelling. A radiological examination had already been carried out on all the joints. Two days after the 99mTc-hIG scan, 10 patients (group 1) underwent 99mTc-WBC scintigraphy and the other 10 (group 2) underwent a 99mTc-NC scan. The results show that the results of 99mTc-hIG and 99mTc-NC scans are in agreement with clinical examinations in the majority of cases. However, a certain number of positive joint scans corresponding to negative clinical examinations was found. The numerical distribution of these results according to the radiological stages seems to show that 99mTc-hIG is more useful than 99mTc-NC in the initial phases of the disease. The 99mTc-WBC scan was negative in a consistent percentage of the joints previously assessed as clinically and 99mTc-hIG scan positive.

Topics: Arthritis, Rheumatoid; Female; Humans; Immunoglobulins; Joints; Leukocytes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Synovitis; Technetium; Technetium Tc 99m Aggregated Albumin; Technetium Tc 99m Exametazime

The aim of this study is to determine whether white blood cell imaging in inflammatory conditions is due to a blood pool effect as a result of an increased vascularity and vascular permeability, or whether cellular migration is the major contributing factor. It will be shown that white cell uptake is a specific phenomenon in the rheumatoid knee joint and not just a blood pool effect.

Topics: Aged; Arthritis, Rheumatoid; Erythrocytes; Female; Gated Blood-Pool Imaging; Humans; Knee Joint; Leukocytes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium; Technetium Tc 99m Aggregated Albumin; Technetium Tc 99m Exametazime

This investigation assessed 99Tcm-HMPAO white blood cell (Tc-WBC) and 67Ga knee uptake indices before and after 90Y treatment in patients with intractable rheumatoid arthritis (RA) and correlated the uptake indices with the clinical score. Sixteen knee joints with RA were treated with intra-articular injection of 185 MBq of 90Y-silicate colloid (Amersham) flushed with 50 mg of hydrocortisone. Clinical score, quantitative 67Ga and Tc-WBC knee uptake indices were obtained before and three weeks after treatment. Our results showed that 9/16 (56%) had a good response and 7/16 (44%) had a poor response to 90Y injection. There was poor correlation between clinical improvement and changes in 67Ga and Tc-WBC knee uptake indices (r = 0.46 and 0.14, respectively). The correlation coefficient between changes in 67Ga and Tc-WBC knee uptake indices was 0.29.

Topics: Adult; Arthritis, Rheumatoid; Female; Gallium Radioisotopes; Humans; Knee Joint; Leukocytes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime; Yttrium Radioisotopes

We quantitated in vivo migration of neutrophils into the knees of patients with rheumatoid arthritis (RA) and osteoarthritis, using 99mtechnetium-hexamethyl-propylene-amineoxime-labeled leukocytes and gamma scintigraphy. Significant neutrophil migration occurred in patients with RA irrespective of disease duration, and it was reduced by 60% following intraarticular steroid injection. The reduction in neutrophil migration correlated with reduction in pain. Leukocyte migration into osteoarthritic joints was also demonstrated, although it was much less than that seen in rheumatoid joints. No significant leukocyte migration into the joints of patients without arthritis was demonstrated. This technique appears to provide a sensitive method for quantitatively assessing the neutrophil component of inflammation in individual joints of patients with arthritis.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cell Movement; Female; Humans; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Neutrophils; Organotechnetium Compounds; Osteoarthritis; Oximes; Pain; Radionuclide Imaging; Technetium Tc 99m Exametazime; Triamcinolone Acetonide

A simplified technique of labelling leucocytes with technetium-99m is described and applied to patients with active rheumatoid arthritis. The clinically active and less active knees in seven patients were imaged and the uptake of labelled leucocytes was measured. The measurements were repeated after local steroid injection into nine painful knees. A 50-80% reduction in leucocyte uptake localized to the region of the synovium was demonstrated in the eight knees which showed clinical responses and a rise of 8% in the non-responder. There was a variable response in the knees that were not injected. 99Tcm leucocyte imaging in rheumatoid arthritis is able to assess objectively joint inflammation and its response to treatment.

Topics: Aged; Arthritis, Rheumatoid; Female; Humans; Injections, Intra-Articular; Isotope Labeling; Knee Joint; Leukocytes; Male; Middle Aged; Organometallic Compounds; Oximes; Radionuclide Imaging; Technetium; Technetium Tc 99m Exametazime; Triamcinolone Acetonide