[99mTc]-PentixaTec SPECT/CT for Imaging of Chemokine Receptor 4 Expression After Myocardial Infarction

Alessandro Liebich; Ralph A Bundschuh; Christian H Pfob; Malte Kircher; Georgine Wienand; Philip Raake; Stephan G Nekolla; Margret Schottelius; Takahiro Higuchi; Maximilian Rieger; Constantin Lapa

doi:10.1161/CIRCIMAGING.124.016992

[^99mTc]-PentixaTec SPECT/CT for Imaging of Chemokine Receptor 4 Expression After Myocardial Infarction

Circ Cardiovasc Imaging. 2024 Nov 13:e016992. doi: 10.1161/CIRCIMAGING.124.016992. Online ahead of print.

Affiliations

¹ Nuclear Medicine, Faculty of Medicine, University of Augsburg, Germany. (A.L., R.A.B., C.H.P., M.K., G.W., C.L.).
² Cardiology, Faculty of Medicine, University of Augsburg, Germany. (P.R., M.R.).
³ Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Germany (S.G.N.).
⁴ Translational Radiopharmaceutical Sciences, Department of Nuclear Medicine and Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland (M.S.).
⁵ Comprehensive Heart Failure Center and Department of Nuclear Medicine, University Hospital Würzburg, Germany (T.H.).

^# Contributed equally.

PMID: 39534974
DOI: 10.1161/CIRCIMAGING.124.016992

Abstract

Background: Accumulation of CXCR4 (C-X-C motif chemokine receptor 4)-positive immune cells after acute myocardial infarction (AMI) can be visualized by positron emission tomography. For a broader clinical application, there is a need for CXCR4-directed radiotracers labeled with isotopes that can be used with single-photon emission computed tomography (SPECT). We report on the detection of CXCR4 expression after AMI in humans using the novel tracer [^99mTc]-PentixaTec.

Methods: In this retrospective analysis, 9 patients with AMI after mechanical revascularization underwent myocardial inflammation imaging with [^99mTc]-PentixaTec SPECT/computed tomography and rest perfusion SPECT imaging. Tracer uptake in the infarcted area, spleen, bone marrow, and blood pool were used for semiquantitative analysis and calculation of signal-to-background ratios. The extent and intensity of SPECT-derived inflammatory changes were compared with serological markers and perfusion defects.

Results: CXCR4-directed SPECT was positive in all patients. Increased CXCR4 expression was only detected in areas with diminished perfusion corresponding to the affected vessel in coronary angiography, with a signal-to-background ratio (infarcted area-to-blood pool) of 2.36±0.74. Uptake in bone marrow and spleen showed a significant correlation with CXCR4 expression in the infarcted areas (r=0.73 and P=0.03 for spleen and r=0.81 and P=0.008 for bone marrow, respectively). The extent and intensity of SPECT-derived inflammatory changes showed no significant association with serum troponin, CK (creatine kinase), leukocyte, or CRP (C-reactive protein) levels.

Conclusions: This is the first report of in vivo CXCR4 imaging after AMI using a ^99mTc-labeled tracer. Increased CXCR4 expression was observed locally in the infarcted region and was related to a systemic inflammatory response in the reticuloendothelial system. This proof-of-concept investigation demonstrates the general feasibility of evaluating the inflammation-related CXCR4 expression in the myocardium after AMI using conventional scintigraphy or SPECT and might, thus, broaden its worldwide application in clinical practice.

Keywords: diagnostic imaging; myocardial infarction; myocytes, cardiac; stroke volume; ventricular function, left.