All examinations had clinical indications and complied to the conditions of the updated Declaration of Helsinki (Section 37, unproven interventions in clinical practice) and the German Pharmaceutical Law (Section 13, 2b). In the controls, the indications for 68Ga-FAPI-04-PET/CT was the possible compassionate use of 177Lu-FAPI-radiotherapy10 and staging. In a patient after MI, the indications for 68Ga-FAPI-04-PET/MR was the compassionate use for chimeric antigen receptor T-cell-therapy11 of myocardial fibrosis and clarification of inflammation and viability after MI. Informed written consent for the investigation and scientific analyses were achieved in all patients.
Finding in Patients with No History of Cardiac Diseases (Control)
Patient population of control group is summarized in Table 1. Normal myocardium showed activity uptake of 68Ga-FAPI-04 of similar intensity as blood pool activity indicating no specific uptake (Figure 1). The averages of maximum and mean standard uptake values (SUVmax, SUVmean) are summarized in Table 2A.
Finding in Patient After Myocardial Infarction
A 33-year-old male was referred to intensive cardiac care unit due to acute STEMI followed by ventricular fibrillation. Return of spontaneous circulation after defibrillation. The present clinical findings at admission are summarized in Table 3. His coronary angiography showed severe sub-occlusive stenosis of medial LAD. Immediately, percutaneous coronary intervention and insertion of one drug eluting stent was performed. The pre- and post-interventional electrocardiograms are summarized in Table 4. Transthoracic echocardiography 5 days after MI showed normal left ventricular diameters, moderate myocardial thickening (interventricular septum 1.3 cm, posterior wall 0.9 cm), normal ventricular wall motion, but moderate left ventricular ejection fraction (LVEF) of 50%. CRP was persistently elevated at 80 mg·L−1. The patient complained about persistent dyspnea and fatigue. To investigate the cardiac fibroblast activation, a dynamic PET/MR imaging was performed 6 days after STEMI immediately after intravenous injection of 165 MBq 68Ga-FAPI-04.
68Ga-FAPI-04-PET of this patient showed focal intense uptake in the anterior and anterior-septal wall, which correlated well with the sub-occluded LAD territory (Figures 2A-D). Almost no uptake was registered in the remote remaining left ventricular wall with activity similar to blood pool. The assessed SUVs are summarized in Table 2B. A small mature scar in inferior apex (arrowhead in Figure 2D in CMR) showed almost no corresponding uptake. Tracer kinetics revealed after rapid peak accumulation a continuous wash-out of the activity in the anterior wall and in its subendocardial border zone (Figure 2F).
The corresponding cardiac magnetic resonance (CMR) revealed in cine sequences a myocardial thickening of the anterior septum (14 mm end-diastolic) and thinning of the inferior apex with hypokinesia. The left ventricular function was moderately reduced (46%). In T2 weighted imaging, the anterior wall showed increased signal, suggesting myocardial edema. In dynamic myocardial perfusion imaging moderate hyperemia of the anterior wall could be observed. Early gadolinium enhancement sequences demonstrated a transmural enhancement of the anterior wall and adjacent septal segments, while late gadolinium enhancement revealed a sub-endocardial enhancement anterior-septal, but also a sub-endocardial enhancement in inferior apex. In T1 Modified Look-Locker Inversion Recovery (MOLLI) (Figure 3A) the anterior wall and adjacent septal segments showed in pre- and post-contrast enhancement pathological T1-relaxation-time and extracellular volume (ECV)-fraction in contrast to remote posterior-basal segments (Table 5). The corresponding 68Ga-FAPI-04-PET/CMR image fusion of the infarcted myocardium presented in Figures 2B-D showed a good correlation of the extent of CMR findings and 68Ga-FAPI-04 intense uptake with the LAD territory. But the extent of intense 68Ga-FAPI-04 uptake was slightly larger than the extent of the pathological CMR findings.
Control CMR 6 months after MI revealed discrete sub-endocardial late enhancement in the inferior apex and anterior-septal wall, indicating scar tissue which is significantly smaller than the extent in the sub-acute of 68Ga-FAPI-04 scan. The left ventricular function recovered to almost normal with LVEF 60%. No hypokinetic ventricular wall motion was detected, except a discrete hypokinesia in the apex. Apart from the anterior-septal sub-endocardial scar (arrowhead in Figure 3B), the assessed pre- and post-contrast T1 MOLLI and ECV (Figure 3B) showed normalization of the findings (Table 5).