Radiotracers to Address Unmet Clinical Needs in Cardiovascular Imaging, Part 2: Inflammation, Fibrosis, Thrombosis, Calcification, and Amyloidosis Imaging

Abstract

Cardiovascular imaging is evolving in response to systemwide trends toward molecular characterization and personalized therapies. The development of new radiotracers for PET and SPECT imaging is central to addressing the numerous unmet diagnostic needs that relate to these changes. In this 2-part review, we discuss select radiotracers that may help address key unmet clinical diagnostic needs in cardiovascular medicine. Part 1 examined key technical considerations pertaining to cardiovascular radiotracer development and reviewed emerging radiotracers for perfusion and neuronal imaging. Part 2 covers radiotracers for imaging cardiovascular inflammation, thrombosis, fibrosis, calcification, and amyloidosis. These radiotracers have the potential to address several unmet needs related to the risk stratification of atheroma, detection of thrombi, and the diagnosis, characterization, and risk stratification of cardiomyopathies. In the first section, we discuss radiotracers targeting various aspects of inflammatory responses in pathologies such as myocardial infarction, myocarditis, sarcoidosis, atherosclerosis, and vasculitis. In a subsequent section, we discuss radiotracers for the detection of systemic and device-related thrombi, such as those targeting fibrin (e.g., ⁶⁴Cu-labeled fibrin-binding probe 8). We also cover emerging radiotracers for the imaging of cardiovascular fibrosis, such as those targeting fibroblast activation protein (e.g., ⁶⁸Ga-fibroblast activation protein inhibitor). Lastly, we briefly review radiotracers for imaging of cardiovascular calcification (¹⁸F-NaF) and amyloidosis (e.g., ^99mTc-pyrophosphate and ¹⁸F-florbetapir).

Keywords: fibrosis; inflammation; molecular imaging; radiotracers; thrombosis.

FIGURE 1.

Differential distributions of inflammation and microcalcification in symptomatic carotid atheroma. Axial noncontrast CT (A), ¹⁸F-FDG PET/CT (B), ¹⁸F-FDG PET (C), CT angiography (D), ¹⁸F-NaF PET/CT (E), and ¹⁸F-NaF PET (F) show symptomatic right carotid artery (purple arrow) and asymptomatic left carotid artery (green arrow); sagittal ¹⁸F-FDG PET/CT (G) shows diffuse uptake in symptomatic carotid artery (arrows); and ¹⁸F-NaF PET (H) shows focal uptake in symptomatic carotid artery (arrow). (Reprinted from (15).)

FIGURE 2.

¹¹C-PK11195 PET imaging of large-vessel vasculitis in patients with systemic inflammatory disorders. ¹¹C-PK11195 PET images fused with CT angiograms demonstrate minimal radiotracer uptake in asymptomatic patient (A) and elevated uptake in symptomatic patient (B). Arrow indicates inflamed region of aortic arch. (Reprinted from (18).)

FIGURE 3.

^99mTc-RYM1 imaging of AAA. (A) Comparison of blood clearance of ^99mTc-RYM1 and ^99mTc-RP805 in mice. (B) Examples of fused ^99mTc-RYM1 SPECT/CT images of AAA in angiotensin II–infused mice at 4 wk after aneurysm induction. Arrows point to tracer uptake in AAA on axial (left), coronal (middle), and sagittal (right) views. (C) Aortic ^99mTc-RYM1 signal in vivo correlates well with MMP activity quantified by ex vivo zymography. %ID = percentage injected dose; AU = arbitrary units; cpv = counts per voxel; p.i. = after injection. (Reprinted from (38).)

FIGURE 4.

Thrombus detection via ¹⁸F-GP1 PET/CT. (A–F) Axial (A and B), coronal (C and D), and parasagittal (E and F) unenhanced CT (top) and corresponding ¹⁸F-GP1 PET/CT images (bottom) demonstrating bioprosthetic valve (BPVT), left atrial appendage (LAA), and left jugular vein thromboses (jv). (G) Anterior maximum-intensity-projection ¹⁸F-GP1 PET image showing distribution of tracer in this patient. (Reprinted from (56).)

FIGURE 5.

Detection of cardiac fibroblast activation via ⁶⁸Ga-FAPI PET/CT. Transaxial images of ⁶⁸Ga-FAPI PET (A) and ⁶⁸Ga-FAPI PET/CT (B) demonstrate left ventricular radiotracer uptake in patient with papillary thyroid cancer. (Reprinted from (67).)