Courtesy of Dr Mark MacAskill and Dr Adriana Tavares, these PET images show detection of regional cardiac inflammation within heart 7 days after myocardial infarction (MI) using a new radiotracer, ¹⁸F-LW223, that specifically targets the 18 kDa translocator protein (TSPO) in vivo.

TSPO is highly expressed within inflammatory cells such as macrophages, and has consequently been used as a marker of inflammation throughout the body, however the clinical adoption of TSPO PET radiotracers in the context of cardiovascular disease has been limited by the lack of validated paradigms for quantifying PET signal in hypoperfused areas using a single technique or scan—previously, quantification of regional tissue inflammation after MI has relied on the use of TSPO PET static imaging and SPECT perfusion static scans for correction of the TSPO PET data. Developing a novel multiparametric analysis approach (using the rate constant for transfer from arterial plasma to tissues, K_1, as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue, BP_TC) has allowed for accurate quantification of regional TSPO expression with a single-scan paradigm.

As shown above, measured ¹⁸F-LW223 PET signal in the infarct area (LV anterior wall) was significantly decreased in a rat MI model compared to naïve animals (A). Representative K₁ and BP_TC images of MI rat demonstrate that most TSPO is expressed within the infarcted myocardium (B), subsequently validated by ex vivo analysis of naïve and MI hearts and immunofluorescent staining of TSPO.

In addition to the favorable in vivo characteristics of ¹⁸F-LW223 and its ability to accurately map macrophage-driven inflammation after MI, its insensitivity to the rs6971 genetic polymorphism in human tissue make it a prime candidate for further clinical translation that could ultimately lead to the development of a prognostic tool for use in patients after MI.

 

The image is taken from a recent study published in the Journal of Nuclear Medicine, in which it was featured as best basic science paper of the month for the April 2021 issue:

MacAskill MG, Stadulyte A, Williams L, Morgan TEF, Sloan NL, Alcaide-Corral CJ, Walton T, Wimberley C, McKenzie CA, Spath N, Mungall W, BouHaidar R, Dweck MR, Gray GA, Newby DE, Lucatelli C, Sutherland A, Pimlott SL, Tavares AAS. Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with ¹⁸F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism. J Nucl Med 2021; 62(4):536-544.