[(18)F]FAPI-42 PET/CT versus [(18)F]FDG PET/CT for imaging of recurrent or metastatic gastrointestinal stromal tumors.

PET has been important for monitoring recurrence and metastasis of Gastrointestinal Stromal Tumors (GISTs) and the selection of therapeutic strategies. A significant portion of GISTs lesions show negative FDG uptake and therefore calls for more tumor-specific imaging biomarkers. This study compared the imaging performance of [18F]FAPI-42 PET/CT and [18F]FDG PET/CT in recurrent or metastatic gastrointestinal stromal tumors (R/M GISTs). This study retrospectively included 35 patients with R/M GISTs who underwent both FAPI PET/CT and FDG PET/CT. The definite diagnosis was confirmed by pathology or follow-up drug treatment effects. The differences in detection rates and tumor-to-background SUVmax ratio (SUVTBR) of different locations between dual-tracer PET/CT were compared. Factors including tumor size, degree of enhancement, type of gene mutation, and targeted treatment potentially influencing the uptake of both tracers were assessed. The excised lesions (n = 3) underwent immunohistochemical staining to verify FAP expression in the tissue. A total of 106 lesions in 35 patients were identified, out of which 38/106 (35.8%) lesions (FAPI + /FDG -) were additionally detected by FAPI PET/CT as compared to that by FDG, including 26 liver metastases, ten peritoneal metastases, one gastrointestinal recurrence, and one bone metastasis. The positive detection rate of FAPI PET/CT for recurrent or metastatic GISTs was higher than that of FDG (80.2% vs. 53.8%,  P< 0.001), especially in liver metastases (87.5% vs. 33.3%, P< 0.001). Moreover, the SUVTBR of liver metastases of GISTs in FAPI PET/CT was higher than that in FDG [2.4 (0.3 to 11.2) vs. 0.9 (0.3 to 6.5), P< 0.001]. The longest diameter of tumors in the FDG-positive group was higher than that of the FDG-negative group (P= 0.005); still, it did not differ between the FAPI-positive group and the FAPI-negative group. No difference in the degree of enhancement was observed between both tracers' positive and negative groups. Besides, the SUVTBR of FDG but not FAPI differed significantly among various gene mutations (P< 0.001) as well as the targeted therapy and no targeted therapy groups (P= 0.001). FAP was expressed in R/M GISTs, and the uptake of FAPI corresponded to the level of FAP expression. In conclusion, FAPI for imaging of R/M GISTs could be superior to FDG, specifically for liver metastases. The uptake of FAPI could reflect the level of FAP expression, and it was independent of tumor size, degree of enhancement, type of gene mutation, and targeted therapy as compared to FDG.

Wu C ，Zhang X ，Zeng Y ，Wu R ，Ding L ，Xia Y ，Chen Z ，Zhang X ，Wang X ... -  《-》

Diagnostic Potential of Supplemental Static and Dynamic (68)Ga-FAPI-46 PET for Primary (18)F-FDG-Negative Pulmonary Lesions.

PET using 68Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, 18F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently 18F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic 68Ga-FAPI-46 PET in the 18F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic 68Ga-FAPI-46 PET in addition to 18F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUVmax, SUVmean, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (68Ga-FAPI-46 in relation to18F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k 1, k 2, k 3, and k 4) were extracted from dynamic 68Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated 68Ga-FAPI-46 uptake, higher TBRs, and higher 68Ga-FAPI-46-to-18F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative 68Ga-FAPI-46-to-18F-FDG ratios regarding SUVmax and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: 68Ga-FAPI-46 PET is a powerful new tool for the assessment of single 18F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.

Röhrich M ，Daum J ，Gutjahr E ，Spektor AM ，Glatting FM ，Sahin YA ，Buchholz HG ，Hoppner J ，Schroeter C ，Mavriopoulou E ，Schlamp K ，Grott M ，Eichhorn F ，Heußel CP ，Kauczor HU ，Kreuter M ，Giesel F ，Schreckenberger M ，Winter H ，Haberkorn U ... -  《-》

[(18)F]FDG and [(68)Ga]Ga-FAPI-04 Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms.

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [18F]FDG and [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [18F]FDG and [68Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [18F]FDG-positive, [68Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUVmean) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Results: Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([18F]FDG: mean TV, 258 ± 588 cm3; HR, 1.024 [per 10 cm3]; 95% CI, 1.007-1.046; P = 0.0204) ([68Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm3; HR, 1.032 [per 10 cm3]; 95% CI, 1.001-1.062; P = 0.0277) and TLU on [18F]FDG PET (mean TLU, 1,931 ± 4,248 cm3; HR, 1.004 [per 10 cm3]; 95% CI, 1.001-1.007; P = 0.0135). Conclusion: The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.

Michalski K ，Kosmala A ，Hartrampf PE ，Heinrich M ，Serfling SE ，Schlötelburg W ，Buck AK ，Meining A ，Werner RA ，Weich A ... -  《-》

Comparisons of Quantitative Parameters of Ga-68-Labelled Fibroblast Activating Protein Inhibitor (FAPI) PET/CT and [(18)F]F-FDG PET/CT in Patients with Liver Malignancies.

To compare quantitative parameters and tumour detection rates of [68 Ga]Ga-FAPI PET/CT with those of dedicated liver PET/MRI and 18F-FDG PET in patients with liver malignancies. Twenty-seven patients (29 imaging studies) with diagnosed or suspected liver malignancies who underwent [68 Ga]Ga-FAPI-46 PET/CT, liver PET/MRI, and [18F]FDG PET/CT between September 2020 and June 2021 were retrospectively analysed. MRI findings were used as the reference standard for diagnosis. The 27 patients had a median age of 68 years (interquartile range: 60-74 years; 21 men). Primary intrahepatic tumours were reported in 13 patients (15 imaging studies) with cholangiocarcinoma (CCA) and in 14 patients with hepatocellular carcinoma (HCC). All intrahepatic lesions detectable on MRI were also detected on [68 Ga]Ga-FAPI-46 PET/CT giving a sensitivity of 100% (19/19), whereas the sensitivity of [18F]FDG PET/CT was 58% (11/19). All intrahepatic lesions were detected on [68 Ga]Ga-FAPI-46 PET/CT, on which they showed higher activity (median SUVmax: 15.61 vs. 5.17; P < .001) and higher target-to-background ratio (TBR; median, 15.90 vs. 1.69, P < .001) than on [18F]FDG, especially in patients with CCA (median TBR, 21.08 vs. 1.47, respectively; P < .001). The uptake positivity rate in regional node metastasis was 100% (12/12) on [68 Ga]Ga-FAPI-46 PET/CT compared with 58% (7/12) on [18F]FDG PET/CT. All patients with distant metastasis (100%, 14/14) were detected on both [18F]FDG and [68 Ga]Ga-FAPI-46 PET/CT imaging, although more distant metastatic lesions were detected on [68 Ga]Ga-FAPI-46 PET/CT than on [18F]FDG (96% (42/44) vs. 89% (39/44), respectively). [68 Ga]Ga-FAPI PET/CT with dedicated liver PET/MRI shows potential for superior detection of hepatic malignancy compared with [18F]FDG PET/CT or MRI alone.

Siripongsatian D ，Promteangtrong C ，Kunawudhi A ，Kiatkittikul P ，Boonkawin N ，Chinnanthachai C ，Jantarato A ，Chotipanich C ... -  《-》

Comparative Study of [(18)F]AlF-LNC1007, [(18)F]FDG, and [(18)F]AlF-NOTA-FAPI-04 PET/CT in Breast Cancer Diagnosis: A Methodological Exploration and Analytical Insight.

Gao H ，Chen J ，Yang Z ，Zhu Z ，He L ，Zhang W ，Chen X ，Zhang J ... -  《-》