Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms

Abstract

Objective. The aetiology and early pathophysiological mechanisms of aortic aneurysm formation are still unknown and challenging to study in vivo. Positron emission tomography (PET) is a potentially valuable instrument for non-invasive in vivo pathophysiological studies. No specific tracer to identify the pathophysiological process of aneurysmal dilatation is yet available, however. The aim of this study was to explore if different PET tracers could be useful to image aneurysmal disease.

Methods and results. Human aneurysmal aortic tissue, collected during elective resection of abdominal aortic aneurysm (AAA) of asymptomatic patients, was investigated in vitro by means of autoradiography with [⁶⁸Ga]CRP-binder targeting C-reactive protein, [¹¹C]DAA1106 targeting translocator protein (18 kDa), [¹¹C]D-deprenyl with unknown target receptor, [¹¹C]deuterium-L-deprenyl targeting astrocytes, [¹⁸F]fluciclatide targeting integrin α_Vβ₃, [⁶⁸Ga]IMP461 and bi-specific antibody TF2 052107 targeting carcinoembryonic antigen, [¹⁸F]F-metomidate targeting mitochondrial cytochrome P-450 species in the adrenal cortex, and [¹⁸F]vorozole targeting aromatase. Of the investigated tracers, only [¹⁸F]fluciclatide exhibited specific binding, whereas the other PET tracers failed to show specific uptake in the investigated tissue and are probably not useful for the intended purpose.

Conclusion. It seems likely that α_Vβ₃ integrin expression in AAA can be visualized with PET and that the α_Vβ₃ selective tracer, [¹⁸F]fluciclatide, may be suitable for in vivo molecular imaging of asymptomatic AAA. Additional evaluation of [¹⁸F]fluciclatide and α_Vβ₃ integrin expression in AAA will be performed in vitro as well as in vivo.

Key words::

• [18F]fluciclatide
• abdominal aortic aneurysm
• autoradiography
• inflammation
• PET
• positron emission tomography

Acknowledgements

We are most grateful to Associate Professor Irina Velikyan, Obaidur Rahman, PhD, and Maria Erlandsson, PhD, for synthesis of DDE, DAA, DED, FVOZ, FMTO, TF2-IMP, and CRPB, which made this study possible. Professor Bengt Långström is acknowledged for his valuable input. We also thank Uppsala Imanet AB and GE Healthcare for granting access to the use of the tracer [¹⁸F]fluciclatide.

Declaration of interest: The study was funded by the Swedish Research Council (Grant K2013-64X-20406-07-3) and an Amersham research grant. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.