PET Imaging of the AT1 receptor with [11C]KR31173

Zober, Tamas G.; Mathews, William B.; Seckin, Esen; Yoo, Sung-eun; Hilton, John; Xia, Jinsong; Sandberg, Kathryn; Ravert, Hayden T.; Dannals, Robert F.; Szabo, Zsolt

doi:10.1016/j.nucmedbio.2005.08.005

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 1 , Pages 5-13, January 2006

PET Imaging of the AT₁ receptor with [¹¹C]KR31173

Tamas G. Zober
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
William B. Mathews
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
Esen Seckin
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
Sung-eun Yoo
- The Center for Biological Modulators, The Korea Research Institute of Chemical Technology, Daejeon 305-343, South Korea
John Hilton
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
Jinsong Xia
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
Kathryn Sandberg
- Department of Medicine, Georgetown University, Washington, DC 20057, USA
Hayden T. Ravert
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
Robert F. Dannals
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
Zsolt Szabo
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA
- Corresponding author. Tel.: +1 410 614 4417; fax: +1 410 614 3896.

Received 12 May 2005; received in revised form 22 August 2005; accepted 23 August 2005.

Abstract

Aim

The goal of this study was to investigate the binding characteristics of [¹¹C]KR31173 and its applicability for PET studies of the AT₁ receptor (AT₁R).

Methods

Ex vivo biodistribution and pharmacology were tested in mice. PET imaging was performed in mice, beagle dogs and a baboon. To assess nonspecific binding, PET imaging was performed both before and after pretreatment with a potent AT₁R antagonist. In the baboon, PET imaging was also performed with the previously developed radioligand [¹¹C]L-159,884 for comparison.

Results

Ex vivo biodistribution studies in mice showed specific binding rates of 80–90% in the adrenals, kidneys, lungs and heart. Specific binding was confirmed in mice using small animal PET. In dogs, renal cortex tissue concentration at 75–95 min postinjection (pi) was 63 nCi/ml per millicurie at a specific binding rate of 95%. In the baboon renal cortex, tissue activity at 55–75 min pi was 345 nCi/ml per millicurie. In the baboon the specific binding of [¹¹C]KR31173 was higher (81%) than the specific binding of [¹¹C]L-159,884 (34%).

Conclusion

[¹¹C]KR31173 shows accumulation and significant specific binding to the AT₁R in the kidneys of mice, dogs and baboon. These findings suggest that this radioligand is suited for imaging the renal cortical AT₁R in multiple species.

Keywords: Angiotensin II, AT₁ receptor, PET, Kidney, Animals