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

This Article 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 Laverman, P. Articles by Boerman, O. C. Search for Related Content PubMed PubMed Citation Articles by Laverman, P. Articles by Boerman, O. C.

A Novel Method to Label Liposomes with ^99mTc by the Hydrazino Nicotinyl Derivative

Departments of Nuclear Medicine and Internal Medicine, University Hospital Nijmegen, Nijmegen
Utrecht Institute for Pharmaceutical Science, Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands

Correspondence: For correspondence and reprints contact: Peter Laverman, University Hospital Nijmegen, Department of Nuclear Medicine, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands.

ABSTRACT

In this study a new ^99mTc labeling method for polyethyleneglycol (PEG)-coated liposomes is described. The in vitro and in vivo characteristics were compared with the conventional ^99mTc-HMPAO-labeled PEG-coated liposomes. Methods: PEG-coated liposomes were labeled with ^99mTc by the hydrazino nicotinyl (HYNIC) derivative of distearoylphosphatidyl-ethanolamine (DSPE) and compared with PEG-coated liposomes labeled with ^99mTc-HMPAO. In vitro stability tests were performed. Biodistribution and imaging characteristics of both liposomal preparations were determined in rats with Staphylococcus aureus infection in the left calf muscle. Results: Per liposome, 230 hydrazine groups were incorporated. The labeling efficiency of the ^99mTc-HYNIC liposomes was greater than 95%, so no postlabeling purification was required, in contrast to the ^99mTc-HMPAO liposomes. The ^99mTc-HYNIC liposomes showed greater in vitro stability than the conventional ^99mTc-HMPAO liposomes. Abscess uptake of the ^99mTc-HYNIC liposomes was significantly greater (1.74 ± 0.38%ID/g versus 1.26 ± 0.29%ID/g, 24 h postinjection, P < 0.03). Furthermore, kidney uptake of the ^99mTc-HYNIC liposomes was one third of the uptake of the ^99mTc-HMPAO liposomes (0.79 ± 0.07%ID/g versus 2.47 ± 0.35%ID/g, 24 h postinjection, P < 0.0001). Conclusion: This new ^99mTc-HYNIC-based labeling method for liposomes is rapid, efficient and easy to perform. Most importantly, the ^99mTc-labeled liposomes have an improved stability and in vivo characteristics. The new labeling method is a major step forward toward a radiopharmaceutical for infection imaging that can be prepared in a one-step procedure within 15 min at room temperature and thus can be applied in every routine clinical practice.

Key Words: ^99mTc • liposomes • radiolabeling • hydrazino nicotinyl • imaging

This article has been cited by other articles:

				A. Bao, B. Goins, R. Klipper, G. Negrete, and W. T. Phillips Direct 99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 419 - 425. [Abstract] [Full Text] [PDF]

				F. A. D. T. G. Wagener, A. Eggert, O. C. Boerman, W. J. G. Oyen, A. Verhofstad, N. G. Abraham, G. Adema, Y. van Kooyk, T. de Witte, and C. G. Figdor Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase Blood, September 15, 2001; 98(6): 1802 - 1811. [Abstract] [Full Text] [PDF]

				P. Laverman, M. G. Carstens, O. C. Boerman, E. Th. M. Dams, W. J. G. Oyen, N. van Rooijen, F. H. M. Corstens, and G. Storm Factors Affecting the Accelerated Blood Clearance of Polyethylene Glycol-Liposomes upon Repeated Injection J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 607 - 612. [Abstract] [Full Text] [PDF]

				P. Laverman, A. H. Brouwers, E. Th. M. Dams, W. J. G. Oyen, G. Storm, N. van Rooijen, F. H. M. Corstens, and O. C. Boerman Preclinical and Clinical Evidence for Disappearance of Long-Circulating Characteristics of Polyethylene Glycol Liposomes at Low Lipid Dose J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 996 - 1001. [Abstract] [Full Text]

				E. T. M. Dams, P. Laverman, W. J. G. Oyen, G. Storm, G. L. Scherphof, J. W. M. van der Meer, F. H. M. Corstens, and O. C. Boerman Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1071 - 1079. [Abstract] [Full Text]