HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kemerink, G. J. Articles by Verbeke, K. Search for Related Content PubMed PubMed Citation Articles by Kemerink, G. J. Articles by Verbeke, K.

Safety, Biodistribution, and Dosimetry of ^99mTc-HYNIC-Annexin V, a Novel Human Recombinant Annexin V for Human Application

¹ Department of Nuclear Medicine, University Hospital Maastricht, Maastricht, The Netherlands
² Department of Nuclear Medicine, University Hospital Gasthuisberg, Leuven, Belgium
³ Laboratory of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, University of Leuven, Leuven, Belgium
⁴ Theseus Imaging Corporation, Boston, Massachusetts

^99mTc-hydrazinonicotinamido (HYNIC)-annexin V is a novel tracer for in vivo imaging of apoptosis. The present study on humans was performed to investigate the safety of ^99mTc-HYNIC-annexin V and to quantify the biodistribution and radiation dose. Methods: Six healthy, male volunteers participated in the study. A dual-head gamma camera was used to acquire conjugate anterior and posterior views. Imaging started with a transmission scan using a ⁵⁷Co-flood source to obtain a map of the local thickness of the volunteer. Approximately 250 MBq of ^99mTc-HYNIC-annexin V were injected intravenously, directly followed by a 30-min dynamic study. Whole-body scans were obtained at about 30 min, 3 h, 6 h, and 24 h after injection. Organ uptake was determined after correction for background, scatter, and attenuation. The MIRDOSE3.1 program was used to calculate organ-absorbed doses and effective dose. Signs of adverse effects were investigated by monitoring renal and liver function, hematology, blood coagulation, and vital signs (blood pressure, pulse, respiration rate, temperature, and electrocardiogram). Results: The kidneys accumulated 49.7 ± 8.1 percentage injected dose (%ID) at 3 h after injection; the liver, 13.1 ± 1.0 %ID; the red marrow, 9.2 ± 1.8 %ID; and the spleen, 4.6 ± 1.6 %ID. More than 90% of the blood activity was cleared with a half-life of 24 ± 3 min. The biologic half-life of the activity registered over the total body was long (69 ± 7 h). Excretion of the activity was almost exclusively through the urine (22.5 ± 3.5 %ID at 24 h), and hardly any activity was seen in the bowel or feces. Absorbed doses were found to be 196 ± 31 µGy/MBq for the kidneys, 41 ± 12 µGy/MBq for the spleen, 16.9 ± 1.3 µGy/MBq for the liver, and 8.4 ± 0.9 µGy/MBq for the red marrow. The effective dose was 11.0 ± 0.8 µSv/MBq, or 2.8 ± 0.2 mSv for the average injected activity of 250 MBq. No adverse effects were observed. Conclusion: ^99mTc-HYNIC-annexin V is a safe radiopharmaceutical, having a favorable biodistribution for imaging of apoptosis in the abdominal as well as thoracic area with an acceptable radiation dose.

Key Words: biosafety • biodistribution • radiation dosimetry • apoptosis • annexin V

This article has been cited by other articles:

				F. G. Blankenberg In Vivo Detection of Apoptosis J. Nucl. Med., June 1, 2008; 49(Suppl_2): 81S - 95S. [Abstract] [Full Text] [PDF]

				S. Rottey, G. Slegers, S. Van Belle, I. Goethals, and C. Van de Wiele Sequential 99mTc-Hydrazinonicotinamide-Annexin V Imaging for Predicting Response to Chemotherapy J. Nucl. Med., November 1, 2006; 47(11): 1813 - 1818. [Abstract] [Full Text] [PDF]

				H. H. Boersma, B. L.J.H. Kietselaer, L. M.L. Stolk, A. Bennaghmouch, L. Hofstra, J. Narula, G. A.K. Heidendal, and C. P.M. Reutelingsperger Past, Present, and Future of Annexin A5: From Protein Discovery to Clinical Applications J. Nucl. Med., December 1, 2005; 46(12): 2035 - 2050. [Abstract] [Full Text] [PDF]

				G. J. Kelloff, K. A. Krohn, S. M. Larson, R. Weissleder, D. A. Mankoff, J. M. Hoffman, J. M. Link, K. Z. Guyton, W. C. Eckelman, H. I. Scher, et al. The Progress and Promise of Molecular Imaging Probes in Oncologic Drug Development Clin. Cancer Res., November 15, 2005; 11(22): 7967 - 7985. [Abstract] [Full Text] [PDF]

				C. Bauer, U. Bauder-Wuest, W. Mier, U. Haberkorn, and M. Eisenhut 131I-Labeled Peptides as Caspase Substrates for Apoptosis Imaging J. Nucl. Med., June 1, 2005; 46(6): 1066 - 1074. [Abstract] [Full Text] [PDF]

				Z. Medarova, S. Bonner-Weir, M. Lipes, and A. Moore Imaging {beta}-Cell Death With a Near-Infrared Probe Diabetes, June 1, 2005; 54(6): 1780 - 1788. [Abstract] [Full Text] [PDF]

				J. F. Tait, C. Smith, and F. G. Blankenberg Structural Requirements for In Vivo Detection of Cell Death with 99mTc-Annexin V J. Nucl. Med., May 1, 2005; 46(5): 807 - 815. [Abstract] [Full Text] [PDF]

				K. J. Yagle, J. F. Eary, J. F. Tait, J. R. Grierson, J. M. Link, B. Lewellen, D. F. Gibson, and K. A. Krohn Evaluation of 18F-Annexin V as a PET Imaging Agent in an Animal Model of Apoptosis J. Nucl. Med., April 1, 2005; 46(4): 658 - 666. [Abstract] [Full Text] [PDF]