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

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jnumed.107.040477v1 48/7/1172    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM 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 Rossin, R. Articles by Welch, M. J. Search for Related Content PubMed PubMed Citation Articles by Rossin, R. Articles by Welch, M. J.

Small-Animal PET of Tumor Angiogenesis Using a ⁷⁶Br-Labeled Human Recombinant Antibody Fragment to the ED-B Domain of Fibronectin

¹ Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and ² Bayer Schering Pharma, Global Drug Discovery, Berlin, Germany

Correspondence: For correspondence or reprints contact: Michael J. Welch, PhD, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus Box 8225, St. Louis, MO 63110. E-mail: welchm{at}wustl.edu

The aim of this study was to image the extra domain B (ED-B) of fibronectin, an angiogenesis-related target, in solid tumors using small-animal PET. Toward this aim, an ED-B fibronectin-binding human antibody derivative (L19-SIP) was labeled with ⁷⁶Br via an enzymatic approach. Biodistribution and imaging studies were performed in human teratoma–bearing mice for up to 48 h after injection. Methods: L19-SIP was labeled with ⁷⁶Br using bromoperoxidase/H₂O₂. The stability of the labeled antibody was tested both in vitro and in vivo. Biodistribution and small-animal imaging studies (PET and CT) were performed in F9-bearing 129/sv mice (n = 3 or 4). Results: The enzymatic radiobromination approach afforded the labeled antibody in high yield (>55%) under mild reaction conditions. ⁷⁶Br-L19-SIP stability in mouse serum proved to be similar to that of the ¹²⁵I-labeled analog (>80% of intact material at 48 h after injection). Fast and specific in vivo targeting was obtained in tumors and other organs expressing ED-B fibronectin (i.e., ovaries and uterus). However, slow renal clearance and persistent activity predominately in blood and stomach suggests partial ⁷⁶Br-L19-SIP debromination in vivo. This debromination was confirmed in a metabolism study in normal mice. The F9 tumors were clearly imaged by small-animal PET at each considered time point, starting at 5 h up to 48 h after injection. Conclusion: ⁷⁶Br-L19-SIP specifically accumulated at the target site, enabling detailed small-animal PET of tumor neovasculature. Therefore, targeting the angiogenesis-associated expression of ED-B fibronectin can be a valuable tool for tumor detection using molecular imaging with PET.

Key Words: angiogenesis • ED-B • fibronectin • L19-SIP • ⁷⁶Br • PET

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2007 48: 11a-12a. [Full Text]  

This article has been cited by other articles:

				A. Almutairi, R. Rossin, M. Shokeen, A. Hagooly, A. Ananth, B. Capoccia, S. Guillaudeu, D. Abendschein, C. J. Anderson, M. J. Welch, et al. Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis PNAS, January 20, 2009; 106(3): 685 - 690. [Abstract] [Full Text] [PDF]

				A. M. Wu Antibodies and Antimatter: The Resurgence of Immuno-PET J. Nucl. Med., January 1, 2009; 50(1): 2 - 5. [Abstract] [Full Text] [PDF]

				G. A.M.S. van Dongen, G. W.M. Visser, M. N. Lub-de Hooge, E. G. de Vries, and L. R. Perk Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications Oncologist, December 1, 2007; 12(12): 1379 - 1389. [Abstract] [Full Text] [PDF]