Table of Contents
International Journal of Molecular Imaging
Volume 2011, Article ID 175352, 9 pages
http://dx.doi.org/10.1155/2011/175352
Research Article

Functional Imaging of Pheochromocytoma with 68Ga-DOTATOC and 68C-HED in a Genetically Defined Rat Model of Multiple Endocrine Neoplasia

1Department of Nuclear Medicine, Johannes Gutenberg University of Mainz, Langenbeck Strasse 1, 55131 Mainz, Germany
2Institute of Pathology, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
3Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
4Department of Medicine, Klinikum Großhadern, Ludwig Maximilians University (LMU), Marchioninistrasse 15, 81377 Munich, Germany
5Department of Nuclear Medicine, Technical University Munich, Ismaninger Strasse 22, 81675 Munich, Germany

Received 12 January 2011; Accepted 7 March 2011

Academic Editor: Björn Wängler

Copyright © 2011 Matthias Miederer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or 11C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P=.03). The increase in mean tumor-to-liver ratio of 11C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P=.0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats.