Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

doi:10.1016/j.nucmedbio.2009.12.005

« Previous Next »Nuclear Medicine and Biology
Volume 37, Issue 3 , Pages 365-370, April 2010

Biodistribution and stability studies of [¹⁸F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

Vijay Gottumukkala
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
Tobias K. Heinrich
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Current address: Molecular Imaging Research, Bayer Schering Pharma, Muellerstrasse 178, 13353 Berlin, Germany.
Amanda Baker
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
Patricia Dunning
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
Frederic H. Fahey
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
S. Ted Treves
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
Alan B. Packard
- Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Corresponding author. Division of Nuclear Medicine, Children's Hospital, Boston, MA 02115, USA. Tel.: +1 617 355 7539; fax: +1 617 730 0619.

Received 12 August 2009; received in revised form 10 December 2009; accepted 11 December 2009. published online 11 February 2010.

Abstract

Introduction

Fluorine-18-labeled rhodamine B was developed as a potential positron emission tomography (PET) tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was therefore undertaken to further evaluate this hypothesis.

Methods

[¹⁸F]Fluoroethylrhodamine B was equilibrated for 2 h at 37°C in human, rat and mouse serum and in phosphate-buffered saline. Samples were removed periodically and assayed by high-performance liquid chromatography. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats.

Results

In vitro stability studies demonstrated that [¹⁸F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but <30% intact in mouse serum. The microPET imaging and biodistribution studies in rats confirmed this result showing high and persistent tracer accumulation in the myocardium compared with the absence of uptake by the myocardium in mice thereby validating our original hypothesis that ¹⁸F-labeled rhodamines should accumulate in the heart.

Conclusions

[¹⁸F]Fluoroethylrhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that ¹⁸F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion.

Keywords: Rhodamine B, Fluorine-18, Myocardial perfusion imaging, Positron emission tomography