Value of [68Ga]Ga‐FAPI‐04 PET imaging in acute coronary syndrome complicated by suspected gastrointestinal malignancies

Early diagnosis of gastrointestinal malignancies in patients with acute coronary syndrome (ACS) is often delayed. The present study aims to demonstrate the value of [68Ga]Ga‐FAPI‐04 PET imaging in ACS with suspected gastrointestinal malignancies. Twelve ACS patients with suspected gastrointestinal malignancies were enrolled, including ST‐elevation myocardial infarction (STEMI) (n = 5), non‐ST‐elevation myocardial infarction (NSTEMI) (n = 5), and unstable angina (UA) (n = 2). All patients underwent coronary angiography (CAG) and [68Ga]Ga‐FAPI‐04 PET/MR or PET/CT within 1 week. All five STEMI and five NSTEMI patients had high [68Ga]Ga‐FAPI‐04 uptake in the injured myocardium compared to remote area (TBR: 2.10 ± 0.72 vs. 0.62 ± 013; p < .001), correlated with peak cTnI level (R = .82, p = .004). No [68Ga]Ga‐FAPI‐04 in the myocardium was found in UA patients. NSTEMI displayed a similar myocardial [68Ga]Ga‐FAPI‐04 intensity as STEMI (p = .42). Compared with STEMI, NSTEMI patients had a significantly delayed door‐to‐balloon time for reperfusion treatment (p = .023). High uptake of [68Ga]Ga‐FAPI‐04 in the gastrointestinal tract was detected in three patients. Because of no myocardial [68Ga]Ga‐FAPI‐04 expression, they discontinued antiplatelet therapy and underwent endoscopy. The rectal, colon, and gastric cancer diagnoses were made by biopsy. The other nine patients showed no accumulation of [68Ga]Ga‐FAPI‐04 beyond the heart, and invasive tumor examinations were delayed. During a median 6‐month follow‐up, no tumor formation was observed. [68Ga]Ga‐FAPI‐04 PET imaging is valuable to assess injured myocardium, detect tumors, and guide invasive examinations in ACS patients with suspected gastrointestinal malignancies.


INTRODUCTION
Acute coronary syndrome (ACS) refers to a group of diseases, including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA).As cancer incidence increases globally, the proportion of ACS patients with gastrointestinal malignancies is also rising. 1 Early diagnosis of gastrointestinal malignancies in ACS patients is difficult and often delayed due to the paradoxical coexistence of antiplatelet therapy and gastrointestinal bleeding (GIB) events induced by tumors or invasive examinations, such as endoscopy and biopsy. 2 Current guidelines recommend that the duration of dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor, should be kept for at least 12 months in ACS patients. 3Nevertheless, interrupting antiplatelet therapy must be considered for at least 5-7 days before invasive examinations, significantly increasing the risk of ischemic events, stent thrombosis, and even cardiac death in ACS patients. 4Hence, there is an urgent need for a noninvasive tool to narrow down the candidates who need to interrupt antiplatelet therapy and perform invasive tumor examinations.It is also essential to simultaneously assess the injured myocardium and predict the ischemic risk for invasive examinations in ACS patients.
Fibroblast activation protein (FAP) is a cell membranebound serine protease overexpressed explicitly in activated fibroblasts and almost undetectable in healthy adult tissues. 5FAP is overexpressed in cancer-associated fibroblasts, the predominant stroma component in the tumor microenvironment, driving tumor progression and metastasis.Recently, gallium-68-labeled FAP inhibitor ([ 68 Ga]Ga-FAPI) PET/CT has been used to detect primary and metastatic lesions in various types of cancers. 6AP is also upregulated in the activated cardiac fibroblasts after acute myocardial infarction (AMI).[ 68 Ga]Ga-FAPI-04 has been reported to be accumulated in the injured myocardium after coronary ligation in rats 7 and patients post infarction. 8[ 68 Ga]Ga-FAPI-04 PET imaging is increasingly valuable for assessing myocardial damage in STEMI patients, whereas the disparity of [ 68 Ga]Ga-FAPI-04 PET imaging in ACS patients, including STEMI, NSTEMI, and UA, remains unclear.
As [ 68 Ga]Ga-FAPI-04 PET imaging has excellent advantages in simultaneously displaying gastrointestinal malignancies and myocardial injury, it may have unique advantages in diagnosing and managing ACS patients with gastrointestinal malignancies.In this pilot study, we aim to demonstrate the feasibility of [ 68 Ga]Ga-FAPI-04 PET imaging in detecting tumors and guiding invasive examinations for ACS patients with high suspicion of gastrointestinal malignancies.Meanwhile, we also try to reveal the value of [ 68 Ga]Ga-FAPI-04 PET imaging in assessing myocardial injury and directing antiplatelet therapy cessation for invasive tumor examinations in ACS patients.

Study population
A total of 12 ACS patients complicated by suspected gastrointestinal malignancies were enrolled in the study.These patients were selected from 1014 ACS patients who underwent coronary angiography (CAG) in our institution between December 2021 and August 2022.Diagnosis and treatment of STEMI, NSTEMI, and UA were carried out according to the current guidelines.As soon as the diagnosis was made, STEMI patients were treated immediately by the primary percutaneous coronary intervention (PCI), bypassing the emergency department. 9NSTEMI and UA patients were admitted to a coronary care unit (CCU) or a general ward and arranged immediate, early, or selective PCI based on risk stratification. 10These patients also presented with melena or hematochezia and elevated tumor markers.The bleeding events were classified based on the Bleeding Academic Research Consortium (BARC) criteria. 11Serial blood samples were tested in all patients, including complete blood count, troponin I (cTnI) (99th percentile > 0.03 μg/L), B-type natriuretic peptide (BNP), liver and renal function tests, cholesterol and triglyceride levels, and serum tumor markers.All patients underwent transthoracic echocardiography.
[ 68 Ga]Ga-FAPI-04 PET/MR or PET/CT was performed approximately 5-7 days after the onset of the ACS symptoms.Eight of 12 ACS patients underwent [ 68 Ga]Ga-FAPI-04 PET/MR imaging.Considering a complete cardiovascular magnetic resonance (CMR) examination requires almost 1 h, we optimized the PET/MR protocol in the present study, and CMR was mainly used for horizontal positioning with high resolution.Our protocol reduced the PET/MR examination time from 1 h to 20 min, which is more suitable and comfortable for ACS patients.The other four presented with MR contraindications (metal inside the body), and PET/CT replaced PET/MR for them.On the day of [ 68 Ga]Ga-FAPI-04 PET/MR or PET/CT examination, no specific preparation (fasting and normal blood glucose level) was requested.A multidisciplinary team diagnosed malignancies based on clinical presentations, radiologic patterns on [ 68 Ga]Ga-FAPI-04 PET/MR or PET/CT, and pathological results.The follow-up period was 1-9 months.
Exclusion criteria were less than 18 years of age, pregnant women, previously performed cardiac surgery or PCI, severe valvular diseases, or cardiomyopathies.This study was approved by the Institutional Ethical Committee of Changhai Hospital (CHEC2020-071) and was performed as a part of a clinical trial (ChiCTR2100052378).Patients were fully informed of the purpose of this study, and written informed consent was obtained from all patients.

Radiopharmaceuticals
Synthesis and radiolabeling of [ 68 Ga]Ga-FAPI-04 were performed using a previously documented method. 12 68Ga was obtained from an in-house 68 Ge-68 Ga generator (ITG).Chelation was performed after the pH adjustment with sodium acetate.Then the reaction mixture was heated to 100 • C for 10 min, and the integrity of the reaction was assessed by radio-liquid chromatography.Before injection, the 68 Ga compounds were processed by solid-phase extraction.The final product was sterile and pyrogenfree, and the radiochemical purity was greater than 95%.

[ 68 Ga]Ga-FAPI-04 PET imaging
PET scans were performed on a PET/CT system or a PET/MR scanner, depending on the presence or absence of metals in the patient's body.Scanning was performed using a Biograph 64 PET/CT equipment (Siemens Health-

Image interpretation
All reconstructed [ 68 Ga]Ga-FAPI-04 PET/MR or PET/CT images were independently evaluated using Syngo.Via (Siemens Healthcare) by two experienced nuclear medicine physicians, blinded to the clinical information.Discrepancies were resolved by consensus.For quantification of standard tracer uptake, circular regions of interest (ROIs) were drawn around the lesions with [ 68 Ga]Ga-FAPI-04 uptake, also in the infarct myocardium remote area and negative cases, for which ROIs of 10 mm in diameter were manually drawn in the myocardium opposing the infarct zone, and in the mid-anterior wall.The ROIs automatically adapted to a tridimensional volume of interest.
The maximum standard uptake value (SUV max ) was automatically derived within this ROI.The target-tobackground ratio (TBR) was calculated as the following formula: divide the tumor's original lesion SUV max by the SUV mean of the liver, and divide the myocardium SUV max by the SUV mean of the heart cavity.The maximum standardized uptake value (SUV max ) of [ 68 Ga]Ga-FAPI-04 was calculated as the formula: maximum pixel value within the ROI activity (MBq/kg)/(injected dose [MBq]/bodyweight [kg]).

Statistical methods
Data are described as mean and standard deviation (SD) or median (range).Categorical variables were compared using Fisher's exact test, and continuous variables using Student's t-test.Pearson's correlation analysis was used to explore the relationship between [ 68 Ga]Ga-FAPI-04 and clinical characteristics.All tests were two-tailed, and a p-value less than .05was considered significant unless otherwise specified.Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc).

Patients' characteristics
Patients' characteristics are summarized in Table 1.All 12 ACS patients, including 10 AMI patients (five STEMI and five NSTEMI) and two UA patients, presented with melena (n = 8), hematochezia (n = 4), and elevated tumor biomarkers (n = 12).The bleeding events were type 2 (n = 7) and 3a (n = 5) based on the BARC criteria.PET imaging was performed within a median of 6 days post ACS symptoms.

Comparison of [ 68 Ga]Ga-FAPI-04 intensity between STEMI and NSTEMI
The clinical characteristics and FAPI intensity between STEMI and NSTEMI patients were further compared (Table 3).NSTEMI patients had a significantly delayed door-to-balloon time for PCI compared to STEMI patients

[ 68 Ga]Ga-FAPI-04 expression beyond the heart in ACS patients
High uptake of [ 68 Ga]Ga-FAPI-04 beyond the heart was detected in three patients (patient #1 in the rectal wall, patient #11 in the sigmoid colon, and patient #12 in the gastric wall).Based on the low or no expression of [ 68 Ga]Ga-FAPI-04 in the myocardium, they discontinued dual antiplatelet therapy (DAPT) for 5 days, and were prescribed low molecular weight heparin (LMWH) as a bridge treatment for the invasive tumor examinations.The diagnoses of rectal, colon, gastric cancer were made by biopsy.
Patient #1 complained of severe chest pain for 1 h.He presented to the emergency department at night, and ECG showed significant ST elevations in leads V1-V5.After loading doses of aspirin and ticagrelor, primary PCI was performed.CAG showed a sub-occluded proximal segment of the left anterior descending (LAD) artery, and a drug-eluting stent (DES) was successfully implanted.Hematochezia and elevated tumor biomarkers were identified on the second day of admission.As shown in Figure 3, [ 68 Ga]Ga-FAPI-04 PET/MR revealed the focal uptake of FAPI in the apex of the heart (SUV max = 2.36, TBR = 1.52), and the rectal wall thickening with significantly high FAPI uptake (SUV max = 5.4,TBR = 2.77).Patient #1 was the first person enrolled in our study, and [ 18 F]FDG PET/MR was also performed to identify the myocardial viability and potential tumors.Compared with [ 68 Ga]Ga-FAPI-04 expression, [ 18 F]FDG PET/MR revealed reduced uptake in the apex of the heart and similar intensity in the rectal wall.The focal expression of [ 68 Ga]Ga-FAPI-04 in the apex of the heart revealed the limited myocardial injury post STEMI.The patient discontinued DAPT and underwent a colonoscopy, showing a large ulcer mass (4 cm in diameter) in the rectum.Pathological examination revealed adenocarcinoma, and he received chemotherapy.
Patient #11 complained of chest pain for 2 days.ECG showed no ST elevation or depression.He was admitted to the general ward with a diagnosis of UA.As shown in Figure 4, CAG showed an 80% LAD stenosis, and a bioabsorbable vascular stent (BVS) was successfully implanted.On the second day post PCI, he complained of chest tightness and melena, and presented with elevated tumor biomarkers.Coronary CTA showed a relatively normal lumen without beam-hardening artefacts compared to the CTA 1 month ago.PET/CT revealed no uptake of [ 68 Ga]Ga-FAPI-04 in the heart, but exhibited high focal uptake in the sigmoid colon (SUV max = 6.6,TBR = 9.12) and prostate (SUV max = 5.4,TBR = 7.46).He received colonography and prostate needle biopsy.Pathological examination revealed colon adenocarcinoma and acinar prostate adenocarcinoma.He was diagnosed with double primary malignant tumors, and received chemotherapy and castration therapy.
Patient #12 was admitted to the hospital with a diagnosis of UA, complaining of chest pain for 3 days.Admission ECG was normal.CAG showed a 70% LAD stenosis, and a DES was successfully implanted.After PCI, she showed melena and elevated tumor biomarkers.As shown in Figure 5, [ 68 Ga]Ga-FAPI-04 PET/MR revealed diffuse uptake in the thickened gastric wall (SUV max = 9.66, TBR = 14.16), but no abnormal uptake in the myocardium.
[ 18 F]FDG PET/CT was also performed, displaying gastric wall thickening, with no [ 18 F]FDG expression.She underwent gastroscopy, and pathological examination showed gastric signet-ring cell carcinoma.She received surgery, and single antiplatelet therapy (SAPT) combined with PPI was prescribed after the surgery.
[ 68 Ga]Ga-FAPI-04 PET imaging was also used to detect the residual tumor in one patient.Patient #7 received an endoscopic submucosal dissection (ESD) for gastric cancer.Pathological examination revealed poorly differentiated adenocarcinoma.Due to the deep positive margins and poorly differentiated carcinoma, he had to undergo laparoscopic gastrectomy.He developed NSTEMI before laparoscopic gastrectomy and thus a CAG examination was performed.As shown in Figure 6, CAG revealed 70% LAD stenosis with normal flow, and no stenosis in the LCX and right coronary artery (RCA).Optical coherence tomography (OCT) investigation in the LAD revealed a vulnerable plaque, and LAD was identified as the culprit vessel.PCI was not performed based on the CAG and OCT findings.He then underwent [ 68 Ga]Ga-FAPI-04 PET/CT to assess myocardium injury and residual tumor after ESD.Focal expression of [ 68 Ga]Ga-FAPI-04 in the interventricular septum was detected (SUV max = 2.04, TBR = 3.26), and LAD was further confirmed as the culprit artery.No accumulation of FAPI beyond the heart was identified.Antiplatelet therapy was discontinued based on the focal injured myocardium, and laparoscopic gastrectomy was performed safely.Pathological examination revealed no viable residual tumor, consistent with the [ 68 Ga]Ga-FAPI-04 PET/CT imaging.
The remaining eight patients showed no accumulation of [ 68 Ga]Ga-FAPI-04 beyond the heart, and invasive examinations were delayed.Due to the GIB events, they switched DAPT to SAPT and PPI.The symptoms of GIB gradually disappeared or improved.These patients were under regular oncology follow-up and close monitoring for F I G U R E 3 A 75-year-old man (patient #1) with STEMI and rectum adenocarcinoma.A DES was implanted in LAD by primary PCI (shown in Figure 1).Hematochezia and elevated tumor biomarkers were identified on the second day of admission.PET/CT showed increased (A) [ 68 Ga]Ga-FAPI-04 and (B) [ 18 F]FDG activity in both tracers in the rectal wall with significant thickening.PET/MR showed high [ 68 Ga]Ga-FAPI-04 uptake (white arrow) in the apex area of the heart, whereas decreased expression of [ 18 F]FDG (yellow arrow) correspondingly.
ischemic events.During a median follow-up, the baseline levels of tumor biomarkers were stable, and no tumor formation was observed.

DISCUSSION
The present study demonstrated the value of

F I G U R E 5
A 58-year-old woman (patient #12) with UA and gastric signet ring cell carcinoma.CAG showed a 70% LAD stenosis, and a DES was successfully implanted (shown in Figure 1).(A) [ 68 Ga]Ga-FAPI-04 PET/MR exhibited diffuse uptake in the thickened gastric wall (white arrow); no abnormal uptake was observed in the myocardium.(B) [ 18 F]FDG PET/CT showed diffusely gastric wall thickening without abnormal tracer uptake.
to the most significant myocardial damage.As soon as the diagnosis is made, STEMI patients should receive life-saving primary PCI, which is critical for myocardial salvage.In contrast, 42% of NSTEMI patients had multivessel diseases, 13 while 25.5% of NSTEMI patients also exhibited occluded or sub-occluded culprit arteries. 14LCX occlusion is often categorized as NSTEMI because of the absence of significant ST-elevation in the standard 12lead ECG.Current guidelines recommend that NSTEMI patients should undergo immediate, early, or selective PCI based on risk stratification. 10However, NSTEMI patients with occluded arteries were identified mostly on F I G U R E 6 A 58-year-old man (patient #7) with gastric cancer and NSTEMI.He received an ESD for gastric cancer and developed NSTEMI after the procedure.[ 68 Ga]Ga-FAPI-04 PET/CT exhibited focal uptake in the interventricular septum (white arrow), and no abnormal tracer uptake was observed in the gastric wall.CAG showed a 70% LAD stenosis (yellow arrow) with normal flow, and OCT revealed a vulnerable plaque formed by a large lipid pool (white arrowheads) and vasa vasorum (red arrows) in the proximal segment, with a minimal lumen area (MLA) 4.25 mm 2 (green circle).delayed cardiac catheterization, with a high risk of major adverse cardiac events and mortality. 15The Global Registry of Acute Coronary Events (GRACE) study reported lower post-discharge mortality in STEMI versus NSTEMI patients, 16 whereas others reported the opposite. 17,18he prognosis between STEMI and NSTEMI remains debatable, and the concrete mechanism is unclear.
We compared the myocardial [ 68 Ga]Ga-FAPI-04 intensity between STEMI and NSTMI patients to observe the underlying pathological processes.The results showed that NSTEMI displayed similar myocardial [ 68 Ga]Ga-FAPI-04 expression levels as STEMI patients.In our study, four of five NSTEMI patients identified the culprit vessel as LCX with sub-occluded or total-occluded lesions during CAG.None of them got immediate PCI.[ 68 Ga]Ga-FAPI-04 was distributed considerably in the lateral or posterior regions of the left ventricle.NSTEMI patients had a significantly delayed door-to-balloon time for PCI, which was 10 times longer than STEMI (31.20 ± 17.81 h vs. 2.80 ± 0.84 h).We speculated that the delayed PCI treatment in NSTEMI led to similar [ 68 Ga]Ga-FAPI-04 expression levels as in STEMI patients.[ 68 Ga]Ga-FAPI-04 PET imaging helped to identify NSTEMI patients with high FAPI intensity in the myocardium.These NSTEMI patients should be labeled with severe myocardial damage and referred for earlier PCI treatment.The molecular information on the underlying cardiac fibroblast activation processes provided by [ 68 Ga]Ga-FAPI-04 PET imaging significantly complements anatomical coronary angiography, which helps to reveal the degrees and distribution of myocardial injury.
Kessler et al. 19 reported that the FAPI uptake area agreed well with the affected coronary territory following AMI.Our study also revealed that FAPI PET imaging could reflect the extent and distribution of myocardial injury in STEMI and NSTEMI patients.Our findings are consistent with the data reported by Kessler et al.Moreover, one NSTEMI patient in our study presented with three-vessel disease, and LAD with moderate stenosis was identified as the culprit artery by FAPI PET imaging.We further demonstrated that FAPI PET imaging could help to determine the culprit artery of NSTEMI patients with three-vessel disease.However, more cases are needed to support our conclusion.
In patient #1, the first patient enrolled in our study, [ 18 F]FDG PET/MR was also used to identify the myocardial viability.Compared with [ 68 Ga]Ga-FAPI-04 PET/MR, [ 18 F]FDG PET/MR revealed reduced uptake of [ 18 F]FDG in the apex of the heart.However, the interpretation of myocardial viability via [ 18 F]FDG PET should combine metabolism and perfusion assessments, which increases the difficulty of assessing myocardial injury post infarction. 20Moreover, oral glucose and intravenous insulin loading are necessary for myocardial evaluation via [ 18 F]FDG PET imaging.As we know, diabetes is a common and significant risk factor for ACS.In the present study, half of ACS patients (50%) have diabetes.
[ 68 Ga]Ga-FAPI-04 PET imaging offers an investigational alternative clinical PET assay of myocardial injury without requiring patient fasting and glucose adjusting.It significantly increases comfort, safety, and satisfaction in ACS patients, especially those with diabetes.Thus, compared to [ 18 F]FDG, [ 68 Ga]Ga-FAPI-04 PET imaging is more straightforward for evaluating myocardial damage in ACS patients.
The 12 ACS patients in our study also presented with melena, hematochezia, or elevated tumor biomarkers.Invasive tumor examinations, including endoscopy and biopsy, are critical in obtaining a definitive diagnosis and proper treatment.A systematic review of endoscopy safety following ACS showed a 9.1% complication rate, with hypotension, cardiac arrhythmias, and repeat ACS as the most frequent complications. 21Given the trade-off between ischemic risk versus pathological examinations, it is necessary to utilize a noninvasive tool to screen ACS patients with suspected gastrointestinal malignancies, narrowing down the group who need to discontinue antiplatelet therapy for invasive tumor examinations.More recent work has revealed that [ 68 Ga]Ga-FAPI PET/CT is superior to [ 18 F]FDG PET/CT for detecting primary tumors, lymph nodes, and distant metastases in gastrointestinal malignancies. 22In our study, three patients were diagnosed with gastrointestinal malignancies by [ 68 Ga]Ga-FAPI-04 PET examination, with high intensity of [ 68 Ga]Ga-FAPI-04 in the rectal wall, sigmoid colon, and gastric wall.
Until now, no ischemic risk tool has been devised for ACS patients complicated by suspected gastrointestinal malignancies requiring antiplatelet therapy cessation and invasive tumor examinations.We found that these three ACS patients with gastrointestinal malignancies had low intensity or no expression of [ 68 Ga]Ga-FAPI-04 in the myocardium, revealing mild myocardial damage and low ischemic risk for antiplatelet therapy cessation and invasive tumor examinations.Under [ 68 Ga]Ga-FAPI-04 PET guidance, we discontinued DAPT for 5 days and prescribed LMWH as a bridge treatment for the invasive tumor examinations.Endoscopy and biopsy confirmed the diagnoses of rectal adenocarcinoma, colon adenocarcinoma, and gastric signet-ring cell carcinoma.Interestingly, in patient #12 with gastric signet-ring cell carcinoma, we performed both [ 68 Ga]Ga-FAPI-04 and [ 18 F]FDG PET imaging.In contrast to the diffuse uptake of [ 68 Ga]Ga-FAPI-04, no expression of [ 18 F]FDG was detected in the thickened gastric wall.Our results appear consistent with a previous study that suggests [ 68 Ga]Ga-FAPI-04 PET has a better detection rate than [ 18 F]FDG for gastric signet-ring cell carcinoma. 23aken together, by simultaneously displaying [ 68 Ga]Ga-FAPI-04 expression in the heart and gastrointestinal tract, [ 68 Ga]Ga-FAPI-04 PET imaging could be a valuable tool to guide antiplatelet therapy cessation and invasive tumor examinations in ACS patients complicated by suspected gastrointestinal malignancies.
Residual tumor after surgery is a critical determinant of clinical outcomes for cancer patients.In our study, patient #7 received ESD for gastric cancer and developed NSTEMI after the procedure.Mild expression of [ 68 Ga]Ga-FAPI-04 in the septum was detected, and there was no accumulation of FAPI in the gastrointestinal tract.Pathological examination confirmed no viable residual tumor after laparoscopic gastrectomy.The negative expression of [ 68 Ga]Ga-FAPI-04 in gastric anastomosis could help dis-tinguish it from the high uptake of [ 18 F]FDG caused by residual gastritis. 22Residual [ 18 F]FDG uptake in the anastomosis after surgery may represent either inflammation or residual tumors.Thus, we propose that [ 68 Ga]Ga-FAPI-04 PET imaging may also be a valuable postoperative imaging technique to detect residual tumors for gastric cancer, and it needs to be verified by further studies.
The remaining eight ACS patients showed the moderate-to-intense intensity of [ 68 Ga]Ga-FAPI-04 in the myocardium, but no accumulation of [ 68 Ga]Ga-FAPI-04 beyond the heart.Based on the high expression of [ 68 Ga]Ga-FAPI-04 in the injured myocardium and negative expression of [ 68 Ga]Ga-FAPI-04 in the gastrointestinal tract, invasive examinations were delayed in the acute phase of the ACS attack.Of course, [ 68 Ga]Ga-FAPI-04 PET imaging cannot replace histopathology as the gold standard for tumor diagnosis.Our multidisciplinary team managed these patients through regular oncologic and ischemic events follow-up.If ACS patients behave more and more like gastrointestinal malignancies, our multidisciplinary team will decide on antiplatelet cessation and invasive tumor examinations after considering both the ischemic and tumor risks during the follow-up.Therefore, our study reveals that the value of negative FAPI expression beyond the heart is to delay the invasive tumor examinations and avoid antiplatelet therapy cessation in the acute phase after the ACS attack.

Limitations
There were several limitations in our study.First, this was a single-center study, and the number of patients was relatively small (n = 12).We cannot eliminate the impact of selection bias in this group.Second, the small sample size and short follow-up duration limited the opportunities for robust multivariable regression analyses.Nevertheless, we propose that [ 68 Ga]Ga-FAPI-04 PET imaging could represent an essential tool with good potential in cardio-oncology.Its value in ACS complicated by suspected gastrointestinal malignancies warrants further validation with a longer follow-up and larger sample size.

CONCLUSIONS
The current study sheds new light on the feasibility of [ 68 Ga]Ga-FAPI-04 PET imaging to identify the injured myocardium, detect potential tumors, and guide invasive examinations in ACS patients with suspected gastrointestinal malignancies.

C O N F L I C T O F I N T E R E S T S TAT E M E N T
The authors declare no conflict of interest.

Figure 1
depicts coronary angiographies and [ 68 Ga]Ga-FAPI-04 PET/MR or PET/CT examinations for all 12 ACS F I G U R E 1 Coronary angiographies and [ 68 Ga]Ga-FAPI-04 PET/MR or PET/CT examinations for all ACS patients complicated by suspected gastrointestinal malignancies.The distribution of [ 68 Ga]Ga-FAPI-04 (white arrows) was consistent with the culprit artery (red arrows) of STEMI and NSTEMI patients.No [ 68 Ga]Ga-FAPI-04 expression was found in UA patients.

TA B L E 3
Comparison of clinical characteristics and FAPI intensity in STEMI and NSTEMI.
[ 68 Ga]Ga-FAPI-04 PET imaging in ACS patients complicated by suspected gastrointestinal malignancies.First, [ 68 Ga]Ga-FAPI-04 PET imaging could assess the intensity and distribution of myocardial injury in STEMI and NSTEMI.No myocardial [ 68 Ga]Ga-FAPI-04 expression was found in UA patients.NSTEMI displayed similar myocardial [ 68 Ga]Ga-FAPI-04 expression levels as STEMI patients.Second, [ 68 Ga]Ga-FAPI-04 PET imaging successfully detected tumors in ACS patients complicated by suspected gastrointestinal malignancies.The high expression of [ 68 Ga]Ga-FAPI-04 beyond the heart could guide invasive examinations and biopsies.Meanwhile, the intensity and distribution of FAPI in the myocardium directed the antiplatelet therapy cessation for invasive tumor examinations.[ 68 Ga]Ga-FAPI-04 PET imaging is a noninvasive tool to assess injured myocardium, detect potential tumors, and guide invasive examinations in ACS patients complicated by suspected gastrointestinal malignancies (Graphical Abstract).ACS is a life-threatening condition with high morbidity and mortality.Our study demonstrated the value of [ 68 Ga]Ga-FAPI-04 in displaying the distribution and degrees of myocardial injury for STEMI and NSTEMI patients noninvasively.The intensity of [ 68 Ga]Ga-FAPI-04 was correlated with the peak cTnI in STEMI and NSTEMI patients, and the distribution of [ 68 Ga]Ga-FAPI-04 presentation was consistent with the culprit artery.STEMI typically presents a total coronary occlusion, leading F I G U R E 4 A 77-year-old man (patient #11) with UA and double primary malignant tumors of the colon and prostate.(A) CAG showed an 80% LAD stenosis, and a BVS was successfully implanted.(B) On the second day post PCI, he presented with melena and elevated tumor biomarkers.Coronary CTA showed a relatively normal lumen compared to the CTA performed 1 month before.(C) [ 68 Ga]Ga-FAPI-04 PET/CT exhibited high focal uptake in the sigmoid colon and prostate, and no abnormal uptake was observed in the myocardium.
[ 68 Ga]Ga-FAPI-04 PET imaging is a promising tool to display injured myocardium in both STEMI and NSTEMI patients.It helps identify NSTEMI patients who should be labeled as having myocardial damage similar to STEMI and should be referred for a more early PCI treatment.In ACS patients with suspected gastrointestinal malignancies, [ 68 Ga]Ga-FAPI-04 PET imaging provides a new perspective to simultaneously detect tumors and myocardial injury.[ 68 Ga]Ga-FAPI-04 PET imaging can guide invasive tumor examinations for ACS patients and predict the ischemic risk during examinations.Although it cannot replace the histopathologic diagnosis, [ 68 Ga]Ga-FAPI-04 PET imaging avoids excessive biopsy and antiplatelet therapy cessation in the acute phase of an ACS attack.As a molecular imaging tool, we believe that [ 68 Ga]Ga-FAPI-04 PET has the potential to illuminate a novel path toward better outcomes in patients with cancer and cardiovascular diseases.A C K N O W L E D G M E N T SThis work was financially supported by the "234 Discipline Climbing Plan" of the First Affiliated Hospital of Naval Medical University (2019YPT002, 2020YPT002), and the Shanghai Science and Technology Innovation Action Plan "Science and Technology Support Project in Biomedical Science" (21S11906000).

TA B L E 1
Summary of clinical characteristics.
Clinical characteristics of each patient.
TA B L E 2