Rheumatoid Arthritis: Bennink RJ

Van Hemert FJ, Voermans C, Van Eck-Smit BL, Bennink RJ. · Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Q J Nucl Med Mol Imaging. · Pubmed #19182731 links to  free full text

Abstract: With growing interest in cell-based scintigraphic diagnosis or therapy monitoring, there is an increasing demand for non-invasive observation and quantification of cell trafficking in the preclinical and clinical setting. Monocytes are members of the human mononuclear phagocyte system originating from a myeloid precursor in the bone. Labeled monocytes are being used for investigation of pathogenesis like atherosclerosis and for monitoring of therapeutic intervention in inflammatory diseases like rheumatoid arthritis. Labeling mononuclear cells at high specific activity without affecting their biological functions allows (delayed) non-invasive imaging with g or PET cameras. Monocytes labeled before their final differentiation into macrophages or dendritic cells may reveal centers of inflammation in a patient and, thereby, contribute to scintigraphic diagnosis. Macrophages or dendritic cells may be in vitro cultured and by means of genetic transformation specified towards specific targets prior to re-injection, an approach with therapeutic potency. This review addresses issues on autologous monocytes, particularly their properties and labeling for non-invasive in vivo radionuclide imaging of chronic inflammation.

Bennink RJ, Thurlings RM, van Hemert FJ, Voermans C, Dohmen SE, van Eck-Smit BL, Tak PP, Busemann-Sokole E. · Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · J Nucl Med. · Pubmed #18632808 links to  free full text

Abstract: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

van Hemert FJ, Thurlings R, Dohmen SE, Voermans C, Tak PP, van Eck-Smit BL, Bennink RJ. · Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1105 AZ Amsterdam, The Netherlands. · Nucl Med Biol. · Pubmed #17998095 No free full text.

Abstract: 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.