68Ga-FAPI PET/CT Visualized Benign Metastasizing Leiomyoma With Bone Invasion.

ABSTRACT: Benign metastasizing leiomyoma (BML) is a rare disease associated with pelvic leiomyoma. We report 18F-FDG and 68Ga-FAPI PET/CT findings in a 51-year-old woman with multiple BMLs. The mass in the abdominopelvic cavity and other metastatic lesions showed highly increased 68Ga-FAPI uptake, whereas uptake of 18F-FDG in those lesions was low. Our report demonstrates that 68Ga-FAPI PET/CT showed a different result in detecting BML to 18F-FDG PET/CT, and 68Ga-FAPI PET/CT may be a promising method for whole-body evaluate metastases.

68Ga-FAPI-04 PET/CT in Non-Small Cell Lung Cancer: Accurate Evaluation of Lymph Node Metastasis and Correlation with Fibroblast Activation Protein Expression.

Fibroblast activation protein (FAP) is a promising diagnostic and therapeutic target in various solid tumors. This study aimed to assess the diagnostic efficiency of 68Ga-labeled FAP inhibitor (FAPI)-04 PET/CT for detecting lymph node metastasis in non-small cell lung cancer (NSCLC) and to investigate the correlation between tumor 68Ga-FAPI-04 uptake and FAP expression. Methods: We retrospectively enrolled 136 participants with suspected or biopsy-confirmed NSCLC who underwent 68Ga-FAPI-04 PET/CT for initial staging. The diagnostic performance of 68Ga-FAPI-04 for the detection of NSCLC was evaluated. The final histopathology or typical imaging features were used as the reference standard. The SUVmax and SUVmean, 68Ga-FAPI-avid tumor volume (FTV), and total lesion FAP expression (TLF) were measured and calculated. FAP immunostaining of tissue specimens was performed. The correlation between 68Ga-FAPI-04 uptake and FAP expression was assessed using the Spearman correlation coefficient. Results: Ninety-one participants (median age, 65 y [interquartile range, 58-70 y]; 69 men) with NSCLC were finally analyzed. In lesion-based analysis, the diagnostic sensitivity and positive predictive value of 68Ga-FAPI-04 PET/CT for detection of the primary tumor were 96.70% (88/91) and 100% (88/88), respectively. In station-based analysis, the diagnostic sensitivity, specificity, and accuracy for the detection of lymph node metastasis were 72.00% (18/25), 93.10% (108/116), and 89.36% (126/141), respectively. Tumor 68Ga-FAPI-04 uptake (SUVmax, SUVmean, FTV, and TLF) correlated positively with FAP expression (r = 0.470, 0.477, 0.582, and 0.608, respectively; all P ≤ 0.001). The volume parameters FTV and TLF correlated strongly with FAP expression in 31 surgical specimens (r = 0.700 and 0.770, respectively; both P < 0.001). Conclusion: 68Ga-FAPI-04 PET/CT had excellent diagnostic efficiency for detecting lymph node metastasis, and 68Ga-FAPI-04 uptake showed a close association with FAP expression in participants with NSCLC.

Increased 68 Ga-FAPI Uptake in Pulmonary Sclerosing Pneumocytoma.

ABSTRACT: Pulmonary sclerosing pneumocytoma is a rare benign neoplasm arising from the primitive respiratory epithelium. Here, we report 68 Ga-FAPI PET/CT findings of pulmonary sclerosing pneumocytoma in a 55-year-old woman. The images showed a solitary pulmonary mass in the left lower lobe with intense 68 Ga-FAPI uptake. Our case illustrates that the sclerosing pneumocytoma should be taken into consideration as one of the differential diagnoses in lung nodules/masses with intense 68 Ga-FAPI uptake.

[68Ga]Ga-FAPI-04 PET/CT in the evaluation of epithelial ovarian cancer: comparison with [18F]F-FDG PET/CT.

PURPOSE: To compare the efficacy of [68Ga]Ga-FAPI-04 PET/CT in primary or recurrent tumors and metastatic lesions of epithelial ovarian cancer (EOC) with that of fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET/CT. METHODS: Forty-nine patients (median age, 57 years; IQR, 51-66 years) with histologically proven primary or relapsed EOC were enrolled. Participants underwent [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT. The detection rate, diagnostic accuracy, semiquantitative parameters, tumor staging, and clinical management of the tracers were compared. The diagnostic performance of [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT was evaluated and compared using surgical pathology. Differences between methods regarding the peritoneal cancer index (PCI) using preoperative imaging, surgical PCI, and tumor markers (CA125, HE4) were also assessed regarding peritoneal metastases. RESULTS: Among the 49 patients, 28 had primary EOC; 21 had relapsed EOC. [68Ga]Ga-FAPI-04 PET/CT outperformed [18F]F-FDG PET/CT in detecting peritoneal metastases (96.8% vs. 83.0%; p < 0.001), retroperitoneal (99.5% vs. 91.4%; p < 0.001), and supradiaphragmatic lymph node metastases (100% vs. 80.4%; p < 0.001). Compared with [18F]F-FDG, [68Ga]Ga-FAPI-04 showed higher SUVmax for peritoneal metastases (17.31 vs. 13.68; p = 0.026) and retroperitoneal (8.72 vs. 6.56; p < 0.001) and supradiaphragmatic lymph node metastases (6.39 vs. 4.20; p < 0.001). Moreover, [68Ga]Ga-FAPI-04 PET/CT showed higher sensitivity compared with [18F]F-FDG PET/CT for detecting metastatic lymph nodes (80.6% vs. 61.3%; p = 0.031) and peritoneal metastases (97.5% vs. 75.9%; p < 0.001), using surgical pathology as the gold standard. Compared with [18F]F-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT led to an upgrade in 14.3% and 33.3% of treatment-naive and relapse participants, resulting in management changes in 10.7% and 19.0% of the patients, respectively. The median PCIFAPI scores were significantly higher than PCIFDG (15 vs. 11; p < 0.001) and positively correlated with CA125 and HE4 levels and surgical PCI. CONCLUSION: [68Ga]Ga-FAPI-04 PET/CT achieved higher sensitivity than [18F]F-FDG PET/CT in the detection and diagnosis of lymph node and peritoneal metastases, suggesting advantages regarding the preoperative staging of patients with EOC and, thereby, improving treatment decision-making. TRIAL REGISTRATION: NCT05034146. Registered February 23, 2021.

The performance of 68Ga-FAPI-04 PET/CT in head and neck squamous cell carcinoma: a prospective comparison with 18F-FDG PET/CT.

PURPOSE: This study was designed to compare the performance of 68Ga-FAPI-04 and 18F-FDG PET/CT for initial staging and recurrence detection of head and neck squamous cell carcinoma (HNSCC). METHODS: Prospectively, 77 patients with histologically proven or highly suspected HNSCC underwent paired 18F-FDG and 68Ga-FAPI-04 PET/CT in a week for either initial staging (n = 67) or restaging (n = 10). The diagnostic performance was compared for the two imaging approaches, especially for N staging. SUVmax, SUVmean, and target-to-background ratio (TBR) were assessed for paired positive lesions. Furthermore, change in management by 68Ga-FAPI-04 PET/CT and histopathologic FAP expression of some lesions were explored. RESULTS: 18F-FDG and 68Ga-FAPI-04 PET/CT exhibited a comparable detection efficiency for primary tumor (100%) and recurrence (62.5%). In the twenty-nine patients receiving neck dissection, 68Ga-FAPI-04 PET/CT showed greater specificity and accuracy in evaluating preoperative N staging than 18F-FDG based on patient (p = 0.031 and p = 0.070), neck side (p = 0.002 and p = 0.006), and neck level (p < 0.001 and p < 0.001). As for distant metastasis, 68Ga-FAPI-04 PET/CT detected more positive lesions than 18F-FDG (25 vs 23) and with higher SUVmax (7.99 ± 9.04 vs 3.62 ± 2.68, p = 0.002) by lesion-based analysis. The type of neck dissection in 9 cases (9/33) was altered by 68Ga-FAPI-04. Overall, clinical management was significantly changed in 10 patients (10/61). Three patients had a follow-up 68Ga-FAPI-04 PET/CT post neoadjuvant therapy: One showed complete remission, and the others showed progression. The 68Ga-FAPI-04 uptake intensity was confirmed to be consistent with FAP expression. CONCLUSION: 68Ga-FAPI-04 outperforms 18F-FDG PET/CT in evaluating preoperative N staging in patients with HNSCC. Furthermore, 68Ga-FAPI-04 PET/CT also shows the potential in clinical management and monitoring response to treatment.

In Vivo Evaluation of a Gallium-68-Labeled Tumor-Tracking Cyanine Dye for Positron Emission Tomography/Near-Infrared Fluorescence Carcinoma Imaging, Image-Guided Surgery, and Photothermal Therapy.

Positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual-modal imaging presents an enticing prospect for tumor diagnosis and surgical navigation. In this study, we developed a novel probe IR808-DOTA for tumor-targeted PET/NIRF imaging, image-guided surgery, and photothermal therapy. This construct had better water solubility and pharmacokinetics than IR808 and had similar photophysical properties, tumor targeting ability, and photothermal anticancer effect to IR808. By a simple labeling process, IR808-DOTA was labeled with gallium-68 and applied as a PET probe for tumor imaging in MCF-7 tumor xenografted mice. IR808-DOTA itself acted as an NIRF imaging agent in the following surgery for intraoperative navigation to aid surgeons in the delineation of tumor margins and visualizing sentinel lymph nodes to facilitate a more thorough tumor resection. Irradiation by laser, IR808-DOTA could prominently inhibit tumor growth in MCF-7 subcutaneous tumor model mice by directly ablating tumor cells, inhibiting tumor proliferation, and promoting tumor cell apoptosis. In summary, 68Ga-DOTA-IR808 could enable a convenient and user-friendly workflow for tumor imaging and guided surgery, and therefore, it may have great prospects for clinical translation as a PET/NIRF dual-modal probe.

Usefulness of [68Ga]FAPI-04 and [18F]FDG PET/CT for the detection of primary tumour and metastatic lesions in gastrointestinal carcinoma: a comparative study.

OBJECTIVE: To assess and compare the diagnostic performance of gallium-68-labelled fibroblast activation protein inhibitor ([68Ga]FAPI-04) and fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in gastrointestinal cancer. METHODS: Fifty-one patients who underwent both [18F]FDG and [68Ga]FAPI-04 PET/CT for initial staging or restaging were enrolled. Histopathological findings, typical radiological appearances, and clinical imaging follow-up were used as the reference standard. The diagnostic performance of the two tracers was calculated and compared. The maximum standardised uptake value (SUVmax), mean SUV (SUVmean), tumour-to-mediastinal blood pool ratio (TBR), and tumour-to-liver ratio (TLR) of primary and metastatic lesions were measured and compared between two imaging modalities. RESULTS: In patient-based analysis, [68Ga]FAPI-04 showed much better diagnostic sensitivity than [18F]FDG in detecting primary tumour (94.44% [17/18] vs. 61.11% [11/18]), postoperative recurrence and metastases (95.65% [22/23] vs. 69.57% [16/23]), and peritoneal carcinomatosis (100% [28/28] vs. 60.71% [17/28]) (all p < 0.05). In lesion-based analysis, [68Ga]FAPI-04 showed higher sensitivity than [18F]FDG for detecting lymph node metastases. In peritoneal carcinomatosis, the median SUVmax (12.12 vs. 7.18) and SUVmean (6.84 vs. 4.11) with [68Ga]FAPI-04 were significantly higher than those with [18F]FDG (all p < 0.005). The TBR and TLR of [68Ga]FAPI-04 were significantly higher than those of [18F]FDG for detecting primary tumour, lymph node, liver, and peritoneal metastases (all p < 0.005). Therapeutic management changed in 13 patients according to [68Ga]FAPI-04 PET/CT compared with conventional imaging. CONCLUSIONS: [68Ga]FAPI-04 is superior to [18F]FDG PET/CT for detecting primary tumour, postoperative recurrence and metastasis, and peritoneal carcinomatosis in gastrointestinal cancer. KEY POINTS: • [68Ga]FAPI-04 PET/CT showed significantly higher sensitivity than [18F]FDG PET/CT in the detection of primary tumour and postoperative recurrence and metastasis in patients with gastrointestinal carcinoma. • [68Ga]FAPI-04 PET/CT had obvious advantages over [18F]FDG PET/CT in the detection of peritoneal carcinomatosis from gastrointestinal carcinoma with a much higher FAPI uptake value, TBR, and TLR. • Although the median SUVmax and SUVmean of [68Ga]FAPI-04 were similar to those of [18F]FDG for the primary tumour, lymph node metastases, and liver metastases in gastrointestinal carcinoma, the TBR and TLR of the SUVmax and SUVmean were significantly higher on [68Ga]FAPI-04 PET/CT, causing the lesions to be displayed more clearly.

68 Ga-FAPI-04 PET/CT in Epithelioid Hemangioendothelioma With Pleura and Bone Metastases.

ABSTRACT: Epithelioid hemangioendothelioma is a low- to intermediate-grade malignant vascular tumor with a slowly progressive course and unpredictable prognosis. We report a case of epithelioid hemangioendothelioma with pleura and bone metastases on 68 Ga-FAPI-04 PET/CT in a 65-year-old woman who underwent surgery and chemotherapy.

68Ga-WRWWWW Is a Potential Positron Emission Tomography Probe for Imaging Inflammatory Diseases by Targeting Formyl Peptide Receptor 2.

Inflammation plays a significant role in many physiological and pathological processes. Molecular imaging could provide functional as well as anatomical information for visualizing various inflammatory diseases. Advancements in imaging tracers for inflammation would improve the accuracy of diagnosis and monitoring, thus facilitating patient care. The positron emission tomography (PET) imaging tracer, 68Ga-labeled antagonist peptide Trp-Arg-Trp-Trp-Trp-Trp (WRWWWW, WRW4), targets formyl peptide receptor 2 (FPR2), which is in turn widely distributed in a variety of tissues and is associated with many inflammatory diseases. In the current study, we aimed to investigate the potential of 68Ga-WRW4 for detecting and monitoring inflammatory lesions in mice. We established an inflammation mouse model by the intramuscular injection of turpentine oil into the left thigh. WRW4 was labeled with 68Ga with an overall radiochemical yield >90% and radiochemical purity >99%. 68Ga-WRW4 uptake in inflamed muscle peaked on day 2 (1.14 ± 0.01 percentage of the injected dose per gram of tissue (%ID/g)) and the uptake ratio of inflammatory/normal muscle also reached a maximum (12.36 ± 2.35). Strong PET signals were detected in the left thigh at 60 min after the injection of 68Ga-WRW4 in experimental mice, but weak or no signals were detected in mice in the blocking and control groups. 68Ga-WRW4 uptake was in agreement with the dynamics of immune cell infiltration during the inflammatory reaction. These results suggest that 68Ga-WRW4 is a promising PET tracer suitable for the noninvasive detection of FPR2 expression and for monitoring inflammatory activity in inflammation-bearing mice.

68Ga-FAPI PET/CT Findings in a Rare Presacral Myxopapillary Ependymoma.

ABSTRACT: Myxopapillary ependymoma is a rare tumor. Most of them occur exclusively in the conus medullaris, cauda equina, or filum terminale. Here, we present the 68Ga-FAPI PET/CT findings in a 37-year-old woman with presacral myxopapillary ependymoma.

Utility of Volumetric Metabolic Parameters on Preoperative FDG PET/CT for Predicting Tumor Lymphovascular Invasion in Non-Small Cell Lung Cancer.

BACKGROUND. Lymphovascular invasion (LVI) is an adverse prognostic indicator in non-small cell lung cancer (NSCLC) and serves as an indication for postoperative adjuvant chemotherapy recommendation after resection. OBJECTIVE. The purpose of this article was to assess the utility of clinicopathologic factors and volumetric metabolic parameters from preoperative FDG PET/CT in predicting primary tumor LVI in NSCLC. METHODS. This retrospective study included 161 patients (mean age, 61.8 ± 8.1 [SD] years; 111 men, 50 women) with surgically confirmed NSCLC who underwent preoperative FDG PET/CT between January 2018 and November 2020. Two nuclear medicine physicians used software to place automated volumes of interest delineating each tumor to record metabolic indexes (SUVmax', SUVmean', and metabolic tumor volume [MTV]), which in turn were used to calculate total lesion glycolysis (TLG). Measurements were first performed independently to determine interobserver agreement using intraclass correlation coefficients (ICCs) and then repeated in consensus. Associations of clinicopathologic and metabolic parameters with tumor LVI status were assessed using t test, Mann-Whitney U test, and chi-square test. Diagnostic performance was assessed using ROC analysis. Multivariable logistic regression analysis was performed to identify independent predictors of tumor LVI. RESULTS. A total of 23.6% (38/161) of patients had LVI. The ICCs were 1.000 for SUVmax', 0.997 for SUVmean', and 0.999 for MTV. Tumors with LVI, compared with tumors without LVI, exhibited higher SUVmax (15.4 ± 5.9 vs 11.7 ± 7.5; p = .006), SUVmean (6.0 ± 1.6 vs 5.1 ± 2.0; p = .009), MTV (median, 15.8 cm3 vs 5.5 cm3; p < .001), and TLG (median, 88.8 vs 24.5; p < .001). Among the metabolic parameters, AUC was highest for MTV (0.704), with an optimal MTV cutoff of 6.4 cm3 yielding sensitivity of 92.1% (35/38), specificity of 56.1% (69/123), PPV of 39.3% (35/89), and NPV of 95.8% (69/72) for LVI. Independent predictors (p < .05) of LVI were MTV (≥ 6.4 cm3; odds ratio [OR], 6.5), category N1 (OR, 6.4) or N2 (OR, 4.0) disease, and category T2 disease (OR, 3.6). These factors combined achieved AUC of 0.854 for LVI. CONCLUSION. The volumetric metabolic parameter MTV from preoperative FDG PET/CT is an independent predictor of tumor LVI in NSCLC. CLINICAL IMPACT. Further studies are warranted to assess the potential role of preoperative prediction of LVI using FDG PET/CT to help guide clinical decision making in NSCLC.

An Unusual Case of Esophageal Carcinosarcoma on 18F-FDG PET/CT.

ABSTRACT: Carcinosarcoma of the esophagus is a rare malignant neoplasm. Here, we report a case of esophageal carcinosarcoma with lymphatic and pulmonary metastases on 18F-FDG PET/CT in a 64-year-old woman.

Unusual Case of an Exophytic Leiomyoma of Rectum Mimicking Malignancy on 18F-FDG PET/CT.

Rectal leiomyoma is an exceedingly rare benign lesion. We here report a case with extraluminal leiomyoma of the middle and lower parts of the rectum showing aberrant hypermetabolism on F-FDG PET/CT in a 54-year-old man.

18F-FDG PET/CT Findings in a Rare Myoepithelial Carcinoma Arising in the Parapharyngeal Space.

Myoepithelial carcinoma is an exceedingly rare malignant neoplasm that most frequently occurs in the salivary gland. We here report a case of myoepithelial carcinoma in a 57-year-old man. Unenhanced and contrast-enhanced CT scans showed an ill-defined, heterogeneous, contrast-enhancing mass in the left parapharyngeal space, which suggested malignancy. F-FDG PET/CT showed a hypermetabolic mass and multiple FDG-avid lymph nodes in the bilateral cervical regions. An incision biopsy was performed, and the pathological examination confirmed the mass to be a myoepithelial carcinoma.