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First published online July 16, 2008
J Nucl Med 2008, doi:10.2967/jnumed.108.051755
© 2008 by Society of Nuclear Medicine
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Biodistribution and Radiation Dosimetry of 99mTc-HMPAO–Labeled Monocytes in Patients with Rheumatoid Arthritis

Roelof J. Bennink 1*, Rogier M. Thurlings 2, Formijn J. van Hemert 1, Carlijn Voermans 3, Serge E. Dohmen 3, Berthe L. van Eck-Smit 1, Paul P. Tak 2, and Ellinor Busemann-Sokole 1

1 Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
2 Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
3 Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands

* To whom correspondence should be addressed. E-mail: r.bennink{at}amc.uva.nl.


   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.

Key Words: joint/muscle, radiobiology/dosimetry, radiopharmaceuticals, biodistribution, monocytes, rheumatoid arthritis







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