title: Comparison between human pharmacokinetics and imaging properties of two conjugation methods for 99mTc-annexin A5.
abstract: 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 (99m)Tc-AnxA5 for in vivo scintigraphy of apoptotic cells, the pharmacokinetics and imaging properties of two radiopharmaceuticals, (99m)Tc-(n-1-imino-4-mercaptobutyl)-AnxA5 (I-AnxA5) and (99m)Tc-(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 (99m)Tc-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.
authors.affiliation: Department of Nuclear Medicine, University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: Boersma
authors.forename: I H
authors.initials: IH
authors.lastname: Liem
authors.forename: G J
authors.initials: GJ
authors.lastname: Kemerink
authors.forename: P W L
authors.initials: PW
authors.lastname: Thimister
authors.forename: L
authors.initials: L
authors.lastname: Hofstra
authors.forename: L M L
authors.initials: LM
authors.lastname: Stolk
authors.forename: W L
authors.initials: WL
authors.lastname: van Heerde
authors.forename: M-T W
authors.initials: MT
authors.lastname: Pakbiers
authors.forename: D
authors.initials: D
authors.lastname: Janssen
authors.forename: A J
authors.initials: AJ
authors.lastname: Beysens
authors.forename: C P M
authors.initials: CP
authors.lastname: Reutelingsperger
authors.forename: G A K
authors.initials: GA
authors.lastname: Heidendal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000097:blood / Q000493:pharmacokinetics*; D017209:Apoptosis; D001682:Biological Availability; D001943:Breast Neoplasms / Q000000981:diagnostic imaging; D009202:Cardiomyopathies / Q000000981:diagnostic imaging*; D006207:Half-Life; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds / Q000097:blood / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics*; D012509:Sarcoma / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C417036:technetium Tc 99m annexin V