Radiotracers to Address Unmet Clinical Needs in Cardiovascular Imaging, Part 1: Technical Considerations and Perfusion and Neuronal Imaging

Abstract

The development of new radiotracers for PET and SPECT is central to addressing unmet diagnostic needs related to systemwide trends toward molecular characterization and personalized therapies in cardiovascular medicine. In the following 2-part review, we discuss select emerging radiotracers that may help address important unmet diagnostic needs in central areas of cardiovascular medicine, such as heart failure, arrhythmias, valvular disease, atherosclerosis, and thrombosis. Part 1 examines key technical considerations pertaining to cardiovascular radiotracer development and reviews emerging radiotracers for perfusion and neuronal imaging. Highlights of this work include discussions on the development of ¹⁸F-flurpiridaz, an emerging PET perfusion tracer, and the development of ¹⁸F-based radiotracers for cardiovascular neuronal imaging, such as ¹⁸F-flubrobenguane. Part 2 of this review covers emerging radiotracers for the imaging of inflammation, fibrosis, thrombosis, calcification, and cardiac amyloidosis.

Keywords: cardiology (basic/technical); cardiology (clinical); inflammation; molecular imaging; myocardial perfusion imaging.

FIGURE 1.

Dual-tracer SPECT imaging of postmyocardial infarction angiogenesis in a canine model using ¹¹¹I-RP748, an α_vβ₃ integrin–targeted agent. Shown are in vivo ¹¹¹In-RP748 SPECT images acquired at 20 and 45min after tracer administration (top 2 rows), ^99mTc-sestamibi images (third row), and fused ^99mTc-sestamibi (green) and 45-min ¹¹In-RP748 (red) images (bottom row) in a dog 3 wk after left anterior descending coronary artery occlusion. ^99mTc-sestamibi perfusion images demonstrate anterior perfusion deficit (yellow arrows). ¹¹¹In-RP748 images demonstrate corresponding increased uptake in hypoperfused region (white arrows). Authors demonstrate that 4-fold increase in ¹¹¹In-RP748 uptake in infarct region corresponds to increased α_vβ₃ expression and histologic evidence of angiogenesis. LV = left ventricle; MIBI = sestamibi; RV = right ventricle; VLA = vertical long axis; HLA = horizontal long axis. (Reprinted with permission of ( 8 ).)

FIGURE 2.

Schematic representation of myocardial uptake of various PET and SPECT perfusion radiotracers in relation to coronary blood flow. Background colors in figure show typical ranges of myocardial blood flow during rest (peach), exercise stress (blue), and pharmacologic vasodilator stress (green). ¹⁵O-H₂O displays nearly linear uptake over physiologic range of blood flow but has limited clinical utility because of suboptimal imaging characteristics. ¹⁸F-flurpiridaz maintains high levels of myocardial extraction at stress-level blood flows, and its uptake-flow curve thus demonstrates only minimal deviation from linearity. By contrast, ^99mTc-sestamibi and ^99mTc-tetrofosmin have more significant reductions in myocardial extraction at moderate and high blood flow rates, and their uptake-flow curves demonstrate significant deviations from linearity. ²⁰¹Tl, ¹³N-NH₃, and ⁸²Rb have intermediate uptake-flow properties. (Reprinted from ( 18 ).)

FIGURE 3.

Representative rest–stress ^99mTc-SPECT and ¹⁸F-flurpiridaz PET images in patient with small heart. Images were acquired in 66-y-old woman with left ventricular end diastolic volume of 82 mL. Reversible anterior perfusion defect is more evident in ¹⁸F-flurpiridaz PET images (B) than ^99mTc-SPECT images (A) and is consistent with 82% stenosis of left anterior descending coronary artery that was found on invasive coronary angiography. Greater sensitivity of ¹⁸F-flurpiridaz PET for detection of myocardial ischemia partially relates to its greater spatial resolution and more linear uptake over physiologic range of blood flow. (Reprinted from ( 17 ).)

FIGURE 4.

Representative ¹²³I-CMICE-013 SPECT perfusion images in a porcine model with left anterior descending coronary artery occlusion during dipyridamole stress. Images were acquired 15 min after injection and provide clear definition of occluded region. (Reprinted from ( 22 ).)

FIGURE 5.

Presynaptic sympathetic imaging with ¹⁸F-FBBG PET. Figure shows representative sequence of whole-body ¹⁸F-FBBG coronal PET images in healthy volunteer. Myocardial signal persists after clearance from liver and surrounding organs. (Reprinted from ( 55 ).)

FIGURE 6.

Pre- and postsynaptic sympathetic imaging with ¹¹C-HED and ¹¹C-CGP 12177 PET. Short axis ¹¹C-HED and ¹¹C-CGP 12177 PET images of patient with congestive heart failure. Significant pre- and postsynaptic mismatch are noted by arrows. (Reprinted from ( 49 ).)