Value of Semi-Quantitative Parameters of 68Ga-FAPI-04 PET/CT in Primary Malignant and Benign Diseases: A Comparison with 18F-FDG.

Objectives: We aimed to compare the value of the semiquantitative parameters of 68Ga-labeled FAP inhibitor (68Ga-FAPI)-04 positron emission tomography/computed tomography (PET/CT) and 18F-fluorodeoxyglucose (18F-FDG) in diagnosing primary malignant and benign diseases. Materials and Methods: 18F-FDG and 68Ga-FAPI-04 PET/CT images of 80 patients were compared. Semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), peak SUV by lean body mass (SULpeak), metabolic tumor volume (or tumor volume of FAPI; FAPI-TV), and TLG (or total lesion activity of FAPI; FAPI-TLA), were automatically obtained using the IntelliSpace Portal image processing workstation with a threshold of 40% SUVmax. The liver blood pool was measured as the background, and the tumor-to-background ratio (TBRliver) was calculated. Results: In all malignant lesions, FAPI-TV and FAPI-TLA were higher in 68Ga-FAPI-04 PET/CT than in 18F-FDG. In the subgroup analysis, 68Ga-FAPI-04 had higher FAPI-TV and FAPI-TLA and lower SUVmax than 18F-FDG had in group A, including gynecological tumor, esophageal, and colorectal cancers. However, six semiquantitative parameters were higher in group B (the other malignant tumors). For the benign diseases, SUVmax, SUVmean, SUVpeak, and SULpeak were lower in 68Ga-FAPI-04 PET/CT than in 18F-FDG. 68Ga-FAPI-04 PET/CT showed a lower liver background and a higher TBRliver than 18F-FDG did. 68Ga-FAPI-04 PET/CT had higher accuracy, sensitivity, and specificity than 18F-FDG had. Conclusion: More accurate semiquantitative parameters and lower abdominal background in 68Ga-FAPI-04 PET/CT make it more competitive in the differential diagnosis of malignant and benign diseases than in 18F-FDG.

Comparison of 68 Ga-FAPI-04 PET/CT with 18 F-FDG PET/CT for diagnosis and staging of gastric and colorectal cancer.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of 68 Ga-FAPI-04 PET/computed tomography (CT) for the diagnosis of primary and metastatic gastric cancer and colorectal cancer lesions as compared with 18 F-FDG PET/CT. MATERIALS AND METHODS: Fifty-nine patients who underwent both 18 F-FDG and 68 Ga-FAPI-04 for initial staging or restaging were enrolled. Histopathological findings and clinical imaging follow-up were used as the reference standard. The diagnostic performance and TNM staging of the two tracers were calculated and compared. The maximum standardized uptake value (SUV max ), tumour-to-mediastinal blood pool ratio (TBR) (lesions SUV max /ascending aorta SUV mean ), and tumour-to-normal liver parenchyma ratio (TLR) (lesions SUV max /liver SUV mean ) of primary and metastatic lesions between two imaging modalities were measured and compared using the Wilcoxon signed-rank test and paired t -test. RESULTS: The two imaging agents are comparable for the detection of primary tumors. The sensitivity of 68 Ga-FAPI-04 PET/CT was higher than that of 18 F-FDG PET/CT for detecting lymph node metastases, peritoneal metastases, liver metastases, and bone metastases. In the patient-based analysis, the TLR for all lesions was significantly higher with 68 Ga-FAPI-04 PET/CT than with 18 F-FDG PET/CT (all P  < 0.05). The accuracy (92.2 vs. 70.3%, P  = 0.002) and sensitivity of 68 Ga-FAPI-04 were significantly higher than that of 18 F-FDG (78.6 vs. 71.4%, P  = 0.011) in determining the lymph node status. 68 Ga-FAPI-04 has a higher accuracy in staging ( P  = 0.041), which is mainly due to the ability of distant metastases detection. CONCLUSION: 68 Ga-FAPI-04 PET/CT may be superior in evaluating the diagnostic efficiency and staging accuracy of gastric and colorectal cancer.

Feasibility of One-Day PET/CT Scanning Protocol with 68Ga-DOTA-FAPI-04 and 18F-FDG for the Detection of Ovarian Cancer Recurrence and Metastasis.

Objective: The objective of this study was to investigate the feasibility of 1-d 68Ga-DOTA-FAPI-04 and 18F-FDG (2-deoxy-2[18F]fluoro-d-glucose) positron emission tomography/computed tomography (PET/CT) for detecting ovarian cancer recurrence and metastasis. Materials and Methods: Fifty-two patients who underwent 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT were divided into 1- and 2-d groups. Image acquisition, injection time, and total waiting time were compared. For the 68Ga-DOTA-FAPI-04 PET/CT scans, low-dose CT scans and low injection dosages were employed, and total radiation dose was assessed for both protocols. The comparative analysis included assessment of patient-based detection rates and lesion-based diagnostic efficacy. Results: The total waiting time was significantly shorter in the 1-d group than in the 2-d group (p = 0.000). The radiation doses stemming from internal radiation and external radiation between the groups showed no differences (p = 0.151 vs. 0.716). In the patient-based analysis, the detection rates for local recurrence, peritoneal, lymph node, and other metastases were not significantly different in both protocols (p ∈ [0.351, 1.000]). For the lesion-based analysis, no differences were noted in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (p ∈ [0.371, 1.000]). Conclusions: The 1-d PET/CT protocol reduced waiting time and exhibited equivalent detectability compared with the 2-d protocol, suggesting its clinical value.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL. RESULTS: A total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell's concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403). CONCLUSIONS: Radiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.

Value of pre-treatment 18F-FDG PET/CT radiomics in predicting the prognosis of stage III-IV colorectal cancer.

Background and purpose: To investigate the value of radiomics features extracted from pre-treatment 18F-FDG PET/CT in predicting the outcomes of stage III-IV colorectal cancer (CRC), which may assist in clinical management strategies and precise treatment of stage III-IV CRC. Materials and methods: 124 patients with pathologically confirmed stage III-IV CRC who underwent pre-treatment 18F-FDG PET/CT scans were enrolled in this study. The least absolute shrinkage and selection operator Cox regression (LASSO-Cox) was used to select radiomics features, and the radiomics scores (Rad-scores) were calculated to build radiomics models. The performance of radiomics models was represented by the concordance index (C-index) and compared with clinical models and complex model. The bootstrap resampling method was used to create validation sets. Additionally, nomograms were developed based on complex models. Results: The C-indices of the radiomics model for predicting PFS and OS were 0.712 (95%CI: 0.680-0.744) and 0.758 (0.728-0.789), respectively. In the clinical model, these values were 0.690 (0.664-0.0.717) and 0.738 (0.709-0.767), respectively. However, in the complex model were 0.734 (0.705-0.762) and 0.780 (0.754-0.807), respectively. The Kaplan-Meier curves demonstrated that the radiomics model could effectively separate patients with stage III-IV stage CRC into high- and low-risk groups (p < 0.001). Multivariate Cox regression analysis confirmed the independent prognostic value of Rad-scores. Conclusion: Pre-treatment 18F-FDG PET/CT radiomics features can stratify the risk of patients with stage III-IV CRC and accurately predict their outcomes. These findings could be clinically valuable for precision treatment and management decisions in stage III-IV CRC.

Value of Presurgical 18F-FDG PET/CT Radiomics for Predicting Mediastinal Lymph Node Metastasis in Patients with Lung Adenocarcinoma.

Objective: The aim of this study was to develop an F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomic model for predicting mediastinal lymph node metastasis (LNM) in presurgical patients with lung adenocarcinoma. Methods: The study enrolled 320 patients with lung adenocarcinoma (288 internal and 32 external cases) and extracted 190 radiomic features using the LIFEx package. Optimal radiomic features to build a radiomic model were selected using the least absolute shrinkage and selection operator algorithm. Logistic regression was used to build the clinical and complex (combined radiomic and clinical variables) models. Results: Ten radiomic features were selected. In the training group, the area under the receiver operating characteristic curve of the complex model was significantly higher than that of the radiomic and clinical models [0.924 (95% CI: 0.887-0.961) vs. 0.863 (95% CI: 0.814-0.912; p = 0.001) and 0.838 (95% CI: 0.783-0.894; p = 0.000), respectively]. The sensitivity, specificity, accuracy, and positive and negative predictive values of the radiomic model were 0.857, 0.790, 0.811, and 0.651 and 0.924, respectively, which were better than that of visual evaluation (0.539, 0.724, 0.667, and 0.472 and 0.775, respectively) and PET semiquantitative analyses (0.619, 0.732, 0.697, and 0.513 and 0.808, respectively). Conclusions: 18F-FDG PET/CT radiomics showed good predictive performance for LNM and improved the N-stage accuracy of lung adenocarcinoma.

68Ga-DOTATATE PET/CT imaging for insulinoma in MEN1 patient with endogenous hyperinsulinemic hypoglycemia: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare and complicated disease that is associated with several endocrine tumors. Here, we report a case of MEN1 associated with insulinoma, parathyroid, and pituitary tumors by 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT). PATIENT CONCERNS: A 49-year-old woman presented with intermittent hypoglycemia for more than a year and developed indistinct consciousness without an apparent trigger. DIAGNOSES: Biochemical results showed abnormally high serum insulin and parathyroid hormone levels. She underwent an Abdominal magnetic resonance imaging revealed a small nodule in the uncinate process of the pancreas, but it did not clarify the nature of the small nodule. Pituitary magnetic resonance imaging scan revealed a micropituitary tumor, and parathyroid imaging showed no abnormalities. 18F-FDG PET/CT showed no apparent abnormal 18F-FDG uptake in the whole body. In contrast, 68Ga-DOTATATE PET/CT imaging showed pathological radiotracer uptake in the pancreatic uncinate process, accompanied by mild radiotracer uptake in the pituitary gland, and no apparent abnormal radiotracer uptake in the parathyroid area. INTERVENTIONS: The patient underwent echoendoscopy for pancreatic uncinate process lesions and surgical resection. OUTCOMES: Histological analysis was suggested of insulinoma of pancreatic neuroendocrine tumor, the Ki-67 index was low (only 1% being positive). LESSONS: This case demonstrates that 68Ga-DOTATATE can be used for the detection of MEN1-related tumors and preoperative localization of small and low-grade insulinomas by PET/CT.

Preparation and Evaluation of (99m)Tc-Epidermal Growth Factor Receptor (EGFR)-Peptide Nucleic Acid for Visualization of EGFR Messenger RNA Expression in Malignant Tumors.

UNLABELLED: Epidermal growth factor receptor (EGFR) is overexpressed in many carcinomas and remains a prime target for diagnostic and therapeutic applications. There is a need to develop noninvasive methods to identify the subset of patients that is most likely to benefit from EGFR-targeted treatment. Noninvasive imaging of EGFR messenger RNA (mRNA) expression may be a useful approach. The aim of this study was to develop a method for preparation of single-photon-emitting probes, (99m)Tc-labeled EGFR mRNA antisense peptide nucleic acid (PNA) ((99m)Tc-EGFR-PNA), and nontargeting control ((99m)Tc-CTL-PNA) and to evaluate their feasibility for imaging EGFR mRNA overexpression in malignant tumors in vivo. METHODS: On the 5' terminus of synthesized single-stranded 17-mer antisense EGFR mRNA antisense PNA and mismatched PNA, a 4-amino-acid (Gly-(D)-Ala-Gly-Gly) linker forming an N4 structure was used for coupling (99m)Tc. Probes were labeled with (99m)Tc by ligand exchange. The radiochemical purity of these (99m)Tc-labeled probes was determined by reversed-phase high-performance liquid chromatography. Cellular uptake, retention, binding specificity, and stability of the probes were studied either in vitro or in vivo. Biodistribution and radionuclide imaging were performed in BALB/c nude mice bearing SKOV3 (EGFR-positive) or MDA-MB-435S (EGFR-negative) carcinoma xenografts, respectively. RESULTS: The average labeling efficiencies of (99m)Tc-EGFR-PNA and (99m)Tc-CTL-PNA were 98.80% ± 1.14% and 98.63% ± 1.36% (mean ± SD, n = 6), respectively, within 6 h at room temperature, and the radiochemical purity of the probes was higher than 95%. (99m)Tc-EGFR-PNA was highly stable in normal saline and fresh human serum at 37°C in vitro and in urine and plasma samples of nude mice after 2-3 h of injection. Cellular uptake and retention ratios of (99m)Tc-EGFR-PNA in SKOV3 cells were higher than those of (99m)Tc-CTL-PNA and the EGFR-negative control. Meanwhile, EGFR mRNA binding (99m)Tc-EGFR-PNA was blocked with an excess of unlabeled EGFR-PNA in SKOV3 cell lines. The biodistribution study demonstrated accumulation of (99m)Tc-EGFR-PNA primarily in the SKOV3 xenografts and in EGFR-expressing organs. Radionuclide imaging demonstrated clear localization of (99m)Tc-EGFR-PNA in the SKOV3 xenografts shortly after injection but not in (99m)Tc-CTL-PNA and the EGFR-negative control. CONCLUSION: (99m)Tc-EGFR-PNA has the potential for imaging EGFR mRNA overexpression in tumors.