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Comparison between human pharmacokinetics and imaging properties of two conjugation methods for ^99mTc-Annexin A5

Departments of ¹ Nuclear Medicine, ² Clinical Pharmacy and Toxicology and ³ Cardiology, University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, ⁴ Central Hematology Laboratory, University Medical Center St. Radboud, P.O. Box 9201, 6500 HB Nijmegen and ⁵ Department of Biochemistry, Cardiovascular Research Institute, University of Maastricht, P.O. Box 616, NL-6200 MD Maastricht, The Netherlands

Correspondence: Hendrikus H Boersma, PharmD, Department of Clinical Pharmacy and Toxicology, University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands

Annexin A5 (AnxA5) is a protein with high affinity for phosphatidyl serine, a phospholipid exposed on the cell surface during apoptosis. This phenomenon has been used for determination of cell death after myocardial infarction. To evaluate the potential of ^99mTc-AnxA5 for in vivo scintigraphy of apoptotic cells, the pharmacokinetics and imaging properties of two radiopharmaceuticals, ^99mTc-(n-1-imino-4-mercaptobutyl)-AnxA5 (I-AnxA5) and ^99mTc-(4,5-bis(thioacetamido)pentanoyl)-AnxA5 (B-AnxA5), were studied. I-AnxA5 was administered intravenously to seven patients and one healthy volunteer, and B-AnxA5 was administered to 12 patients. All patients in the pharmacokinetic study had myocardial disease. Additionally, imaging was performed in a patient with acute myocardial infarction, as well as in three patients with different malignancies. The plasma concentration, excretion and biodistribution of ^99mTc-AnxA5 were measured, as well as levels of AnxA5 antigen. The kinetic data of both radiopharmaceuticals in plasma fitted a two-compartment model. Both preparations had similar half-lives, but a different distribution over the two compartments. Plasma levels of AnxA5 antigen showed a broad variation. Both radiopharmaceuticals accumulated in the kidney, liver and gut. B-AnxA5 was excreted significantly faster than I-AnxA5. Both compounds can be used for imaging of the head/neck region, the thorax and the extremities. B-AnxA5 has a faster clearance and a lower radiation dose. Imaging of apoptosis in the abdomen will be difficult with both radiopharmaceuticals, and especially with B-AnxA5 because of its faster appearance in the gut.

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