JNM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

First published online June 15, 2007
J Nucl Med 2007, doi:10.2967/jnumed.107.040477
 © 2007 by Society of Nuclear Medicine
This Article
Right arrow Full Text (Publish Ahead of Print[PDF])
Right arrow All Versions of this Article:
jnumed.107.040477v1
48/7/1172    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rossin, R.
Right arrow Articles by Welch, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rossin, R.
Right arrow 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

Raffaella Rossin 1, Dietmar Berndorff 2, Matthias Friebe 2, Ludger M. Dinkelborg 2, and Michael J. Welch 1*

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

* To whom correspondence should be addressed. E-mail: welchm{at}wustl.edu.


  Abstract

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




This article has been cited by other articles:


Home page
 The OncologistHome page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY THE JOURNAL OF NUCLEAR MEDICINE
Copyright © 2007 by the Society of Nuclear Medicine.