The inferior performance of [68Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [177Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors.

PURPOSE: We aimed to investigate the potential of [68Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy. METHODS: Patients who received at least two cycles of [177Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI-04 PET/CT within 3 weeks. The number of PET-positive lesions related to NETs and tumor sites was documented. Mann-Whitney U and chi-square tests were used to compare SUVmax levels of tracers and the number of detected metastases. RESULTS: Twelve patients (7 male, 5 female) who met the eligibility criteria were included in the study. Ten patients had grade 1-2 NET of various origins, and two had paraganglioma and pheochromocytoma. One hundred ninety-eight of 230 lesions (86%) were SSTR positive with a median SUVmax of 16.6 (2.2-76.5), and 88 of 230 lesions (38.2%) were [68Ga]Ga-FAPI-04 positive with a median SUVmax of 5.1 (2.3-21). Median SUVmax level and detected number of tumors were significantly higher in [68Ga]Ga-DOTATATE PET/CT (p=<0.001). [68Ga]Ga-FAPI-04 PET/CT was completely (n:2) or almost completely (n:3) negative in 5 (42%) patients. Two (17%) patients had flip-flop SSTR/FAPI uptake in tumors. In four patients (33%), tumor uptake or the number of PET-positive lesions was inferior in [68Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [68Ga]Ga-FAPI-04 PET/CT. Low-dose [177Lu]Lu-FAPI-46 dosimetry was performed on the FAPI-dominant patient; absorbed radiation doses per GBq were 1.26 Gy, 0.36 Gy, 0.32 Gy, and 0.2 Gy for kidneys, liver, spleen, and total body, respectively. The mean absorbed dose per GBq was 0.33 Gy for liver mass and 0.41 Gy for metastatic lymph nodes. CONCLUSION: Our preliminary results demonstrated that [68Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy and had a limited role as an alternative diagnostic or theranostic agent. Further investigations with a larger patient population are required to determine the impact of [68Ga]Ga-FAPI-04 PET/CT on NETs.

Potential application of 68Ga-FAPI PET/CT for diagnosing cardiac sarcoidosis.

Detecting cardiac sarcoidosis; a potentially life-threatening condition is challenging and requires a multimodality imaging approach using echocardiography, PET/CT and CMR. Although 18F-FDG is the recommended PET tracer for evaluating cardiac sarcoidosis, it is limited by physiological cardiac FDG uptake and requires stringent patient preparation/ dietary modifications before imaging. We hereby present a case of cardiac sarcoidosis demonstrating myocardial FAPI uptake on cardiac PET, highlighting the potential role of 68Ga-FAPI PET in the evaluation of cardiac sarcoidosis.

Head-To-Head Comparison of 68Ga-FAPI PET/CT and FDG PET/CT for the Detection of Peritoneal Metastases: Systematic Review and Meta-Analysis.

BACKGROUND. FDG PET/CT has limited diagnostic performance in the detection of peritoneal metastasis (PM). Gallium-68-labeled fibroblast activation protein inhibitor (FAPI) targets tumor stroma, leading to high accumulation across cancer types. OBJECTIVE. The purpose of this study was to conduct a meta-analysis to compare the diagnostic performances of 68Ga-FAPI PET/CT and FDG PET/CT in detecting PM on the basis of studies providing head-to-head comparisons between the two tests. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Library databases were searched through July 2022 to identify studies reporting head-to-head comparison of 68Ga-FAPI PET/CT and FDG PET/CT for detection of PM. The reference standard was classified as histopathology for all patients or as a combination of histopathologic, clinical, imaging, laboratory, and follow-up information (multidisciplinary reference standard). A random-effects statistical model was applied to conduct a meta-analysis of the diagnostic performances of the tests in patient-based and lesion-based analyses. The QUADAS-2 and QUADAS Comparative tools were used to assess study quality. EVIDENCE SYNTHESIS. Eleven studies were included. Patient-based analysis was reported in nine studies including 340 patients, and lesion-based analysis was reported in four studies including 222 lesions. The pooled sensitivity of 68Ga-FAPI PET/CT was significantly higher than that of FDG PET/CT in patient-based analysis (98.2% [95% CI, 96.1-100.0%] vs 55.9% [95% CI, 33.9-77.9%]) and lesion-based analysis (99.9% [95% CI, 99.5-100.0%] vs 27.3% [95% CI, 11.2-43.4%]). Eight studies were rated at high risk of bias in the reference standard domain because the multidisciplinary reference standard was not sufficiently explained and may have included one of the two index tests, which would have artificially increased sensitivity. In three studies specificity was reported as 100.0% for both tests; these studies were considered at uncertain risk of bias in the patient selection domain because patients with benign peritoneal conditions may have been excluded, resulting in underestimation of potential false-positive results. CONCLUSION. The current evidence suggests excellent sensitivity of 68Ga-FAPI PET/CT for the detection of PM in comparison with poorer sensitivity of FDG PET/CT. However, most included studies had high risk of bias. Further studies are needed to more convincingly characterize true- and false-positive results. CLINICAL IMPACT. The sensitivity of 68Ga-FAPI PET/CT may be substantially greater than that of FDG PET/CT for the evaluation of PM, facilitating surgical planning and candidate selection.

FAP imaging in rare cancer entities-first clinical experience in a broad spectrum of malignancies.

PURPOSE: 68 Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors. MATERIAL AND METHODS: Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a 68 Ga-FAPI-PET/CT scan. Fourteen women and 41 men (median age 60) were included within the following subgroups: cancer of unknown primary (n = 10), head and neck cancer (n = 13), gastrointestinal and biliary-pancreatic cancer (n = 17), urinary tract cancer (n = 4), neuroendocrine cancer (n = 4), and others (n = 7). Tracer uptake was quantified by standardized uptake values SUVmax and SUVmean and the tumor-to-background ratio (TBR) was determined (SUVmax tumor/SUVmean organ). RESULTS: In 20 out of 55 patients, the primary tumor was identified and 31 patients presented metastases (n = 88), characterized by a high mean SUVmax in primary (10.1) and metastatic lesions (7.6). The highest uptake was observed in liver metastases (n = 6) with a mean SUVmax of 9.8 and a high TBR of 8.7, closely followed by peritoneal carcinomatosis (n = 16) presenting a mean SUVmax of 9.8 and an excellent TBR of 29.6. In terms of the included subgroups, the highest uptake regarding mean SUVmax was determined in gastrointestinal and biliary-pancreatic cancer with 9.8 followed closely by urinary tract cancer with 9.5 and head and neck cancer (9.1). CONCLUSION: Due to excellent tumor visualization and, thereby, sharp contrasts in terms of high TBRs in primary and metastatic lesions in different rare malignancies, 68 Ga-FAPI-PET/CT crystallizes as a powerful and valuable imaging tool, particularly with respect to epithelial carcinomas, and therefore an enhancement to standard diagnostics imaging methodologies. The realization of further and prospective studies is of large importance to confirm the potential of FAP imaging in oncology.

Prognostic significance of 68 Ga-FAPI PET/CT in patients with bone metastases in various cancers.

OBJECTIVE: This study aimed to compare 18FDGPET/CT in patients who develop bone metastases due to various cancers and to investigate the prognostic significance of the 68FAPI-PET/CT SUVmax value for survival. METHODS: Patients with bone metastases who underwent both 68 Ga-FAPI PET/CT and 18FDGPET/CT within a 1 week period were included in this retrospective study. The effect of the SUVmax value of bone lesions on overall survival was analyzed. RESULTS: A total of 75 eligible patients with 139 bone lesions were included in this study. The median age of the patients was 55 (30-83) and 48(64%) patients were newly diagnosed. The primary lesion median 68 Ga-FAPI PET/CT SUVmax value was higher than the median 18FDGPET/CT SUVmax (10.75 versus 6.7). Bone lesions 68 Ga-FAPI PET/CT SUVmax median (IQR) were 7.8 (4.6-13.2), and 18FDGPET/CT SUVmax of bone lesions were 5.9 (3.8-8.2). More bone lesions were detected on 68 Ga-FAPI PET/CT than on 18FDGPET/CT(median IQR 4 [1-9] versus 2 [1-6] (p = 0.014). The extra lesions observed on 68 Ga-FAPI PET/CT were mostly sclerotic bone lesions (p = 0.001).68 Ga-FAPI PET/CT SUVmax was significantly higher in vertebra and thorax lesions (p = 0.011 and p = 0.018, respectively). While the bone lesion 68 Ga-FAPI PET/CT SUVmax affected the OS, the 18FDGPET/CT SUVmax value did not affect the OS (p < 0.001 and p = 0.079, respectively). In ROC analysis, a cut-off-off value of 68 Ga-FAPI PET/CT SUVmax > 7.7 was found for OS (AUC: 0.619). The median OS in the group above the cut-off value was worse than that in the group below the cut-off value (32 versus 45) months (p = 0.002). In the multivariate analysis for OS, the 68 Ga-FAPI PET/CT SUVmax of bone lesions was an important parameter, as well as cancer subtype, ALP level, and disease occurrence. CONCLUSIONS: 68 Ga-FAPI PET/CT detected more bone lesions and higher SUVmax values than 18FDGPET/CT in various cancers. The prognostic value of the SUVmax value of 68 Ga-FAPI PET/CT bone lesions was observed regardless of disease subtype.

68Ga-FAPI PET/CT as an Alternative to 18F-FDG PET/CT in the Imaging of Invasive Lobular Breast Carcinoma.

Accurate staging of invasive lobular carcinoma (ILC), a subtype of breast cancer, is vital for effective clinical management. Although 18F-FDG PET/CT is a commonly used tool, its efficacy varies across different histologic subtypes. To mitigate this challenge, our investigation delves into the potential utility of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT as an alternative for staging ILC, aiming to address a significant research gap using a more expansive patient cohort than the smaller samples commonly found in the existing literature. Methods: In this retrospective analysis, women diagnosed with primary ILC of the breast underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/CT. Both modalities were compared across all lesion locations with the used reference standard. The interval between scans was 1 wk, without any intervening treatments. Lesions were categorized visually, and tracer activity was analyzed using SUVmax, tumor-to-background uptake ratio, and uptake ratios. Both modalities were compared across various parameters, and statistical analysis was performed using SPSS 22.0. A P value of less than 0.05 was chosen to determine statistical significance. Results: The study included 23 female ILC patients (mean age, 51 y) with hormone-positive, human epidermal growth factor receptor type 2-negative tumors. Most (65%) had the luminal A subtype. 68Ga-FAPI PET/CT outperformed 18F-FDG PET/CT, with higher tumoral activity and tumor-to-background uptake ratios (P < 0.001). Primary tumors showed significantly increased uptake with 68Ga-FAPI PET/CT (P < 0.001), detecting additional foci, including multicentric cancer. Axillary lymph node metastases were more frequent and had higher uptake values with 68Ga-FAPI PET/CT (P = 0.012). Moreover, 68Ga-FAPI PET/CT identified more lesions, including bone and liver metastases. Pathologic features did not significantly correlate with imaging modalities, but a positive correlation was observed between peritumoral lymphocyte ratio and 68Ga-FAPI PET/CT-to-18F-FDG PET/CT uptake ratios (P = 0.026). Conclusion: This study underscores 68Ga-FAPI PET/CT's superiority over 18F-FDG PET/CT for ILC. 68Ga-FAPI PET/CT excels in detecting primary breast masses, axillary lymph nodes, and distant metastases; can complement 18F-FDG PET/CT in ILC; and holds potential as an alternative imaging method in future studies.

Oncologic Staging with 68Ga-FAPI PET/CT Demonstrates a Lower Rate of Nonspecific Lymph Node Findings Than 18F-FDG PET/CT.

Nonspecific lymph node uptake on 18F-FDG PET/CT imaging is a significant pitfall for tumor staging. Fibroblast activation protein α expression on cancer-associated fibroblasts and some tumor cells is less sensitive to acute inflammatory stimuli, and fibroblast activation protein-directed PET may overcome this limitation. Methods: Eighteen patients from our prospective observational study underwent 18F-FDG and 68Ga fibroblast activation protein inhibitor (FAPI) PET/CT scans within a median of 2 d (range, 0-22 d). Lymph nodes were assessed on histopathology and compared with SUV measurements. Results: On a per-patient basis, lymph nodes were rated malignant in 10 (56%) versus 7 (39%) patients by 18F-FDG PET/CT versus 68Ga-FAPI PET/CT scans, respectively, with a respective accuracy of 55% versus 94% for true lymph node metastases. Five of 6 (83%) false-positive nodes on the 18F-FDG PET/CT scans were rated true negative by the 68Ga-FAPI PET/CT scans. On a per-lesion basis, tumor detection rates were similar (85/89 lesions, 96%). Conclusion: 68Ga-FAPI PET/CT imaging demonstrated higher accuracy for true nodal involvement and therefore has the potential to replace 18F-FDG PET/CT imaging for cancer staging.