[(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 ... -  《-》

Exploring the Potential Value of [ 68 Ga]Ga-FAPI-46 PET/CT for Molecular Assessment of Fibroblast Activation in Interstitial Lung Disease : A Single-Center Pilot Study.

The aim of the study was to evaluate the association of high-resolution computed tomography (HRCT) findings with pulmonary fibrotic activity in the corresponding regions using [ 68 Ga]Ga-fibroblast activation fibroblast inhibitor (FAPI) PET/CT in patients with interstitial lung disease (ILD). Additionally, the potential of [ 68 Ga]Ga-FAPI-46 PET/CT for evaluating the active fibrosis process and 99m Tc-MIBI scintigraphy for assessing the inflammatory process in ILD patients was also assessed. In this pilot study, 20 ILD patients underwent [ 68 Ga]Ga-FAPI-46 PET/CT and 99m Tc-MIBI SPECT/CT. Additionally, 10 patients without lung or thoracic involvement who were undergoing [ 68 Ga]Ga-FAPI PET/CT for cancer detection were enrolled in the control group. The images were evaluated both visually and semiquantitatively and also compared with HRCT and pulmonary function tests. Multiple quantitative parameters were derived from the lung segments in the PET scan, including SUV max , SUV mean , maximum target-to-liver ratio, mean target-to-liver ratio (TLR mean ), and total lesion FAPI expression for the entire lung, as well as its lobes and zones. Additionally, the maximum Hounsfield unit (HU) and mean HU in HRCT were calculated for the whole lung as well as its lobes and zones. Furthermore, an HRCT fibrosis score (HFS) was defined according to the HRCT findings. Twenty ILD patients with a mean age of 58.70 (SD, 11.09) years were enrolled. Additionally, 10 control patients were enrolled with a mean age of 57.70 (SD, 15.19) years. Based on visual assessment, the FAPI scan was positive in 12 (60%) patients. Similarly, the MIBI scan was positive in 12 (60%) patients. In the 20 ILD cases, both scans were positive in 6 cases, and both were negative in 2 cases. Six cases showed FAPI-negative and MIBI-positive results, whereas another 6 cases showed FAPI-positive and MIBI-negative results. Comparing the control and ILD patients, there was a significant difference in SUV max , SUV mean , total lesion FAPI expression, TLR mean , maximum HU, and mean HU ( P < 0.05). When comparing HFS with PET-derived parameters in zones, a significant positive correlation was found between HFS and SUV mean , SUV max , maximum target-to-liver ratio, and TLR mean ( P < 0.05). Additionally, a significant difference was noted between FAPI results and HFS ( P = 0.003). An ancillary finding, 9 of 20 (45%) ILD patients showed intense FAPI uptakes in gallbladder, whereas none of the 10 in the control group showed such uptake. The present study may suggest that combining [ 68 Ga]Ga-FAPI PET/CT and 99m Tc-MIBI SPECT/CT yields an additive effect for evaluating ILD-related fibrosis and inflammatory processes over using either modality alone. Furthermore, it appears that [ 68 Ga]Ga-FAPI PET/CT has the potential to ascertain levels of fibrotic activity from population of resident fibroblasts, active fibroblasts, and scar maturation among ILD patients based on their HRCT patterns.

Bahtouee M ，Jafari E ，Khazaei M ，Aram N ，Amini A ，Jokar N ，Ahmadzadehfar H ，Gholamrezanezhad A ，Assadi M ... -  《-》

Detection of tumour heterogeneity in patients with advanced, metastatic castration-resistant prostate cancer on [(68)Ga]Ga-/[(18)F]F-PSMA-11/-1007, [(68)Ga]Ga-FAPI-46 and 2-[(18)F]FDG PET/CT: a pilot study.

In metastatic castration-resistant prostate cancer (mCRPC), some patients show low/absent PSMA expression in tumour lesions on positron emission tomography (PET) scans, indicating heterogeneity and heightened risk of non-response to PSMA-RLT (radioligand therapy). Imaging cancer-associated fibroblasts and glucose uptake may further characterise tumour heterogeneity in mCRPC patients. Here, we aimed to evaluate tumour heterogeneity and its potential implications for management in mCRPC patients assessed for PSMA-RLT using [68Ga]Ga-FAPI-46, 2-[18F]FDG and [68Ga]Ga-/[18F]F-PSMA-11/-1007 PET. Patients with advanced, progressive mCRPC underwent clinical [68Ga]Ga-/[18F]F-PSMA-11/-1007, 2-[18F]FDG and [68Ga]Ga-FAPI-46 PET/CT to evaluate treatment with PSMA-directed RLT. Tumour detection/semiquantitative parameters were compared on a per-lesion/-region basis. Two phenotypes were defined: Criteria for the mixed phenotype were: (a) PSMA-negative findings for lymph node metastases ≥ 2.5 cm, any solid organ metastases ≥ 1.0 cm, or bone metastases with soft tissue component ≥ 1.0 cm, (b) low [68Ga]Ga-/[18F]F-PSMA-11/-1007 uptake and/or (c) balanced tumour uptake of all radioligands. The PSMA-dominant phenotype was assigned if the criteria were not met. In ten patients, 472 lesions were detected on all imaging modalities (miTNM regions: M1b: 327 (69.3%), M1a: 95 (20.1%), N1: 26 (5.5%), M1c: 18 (3.8%), T: 5 (1.1%) and Tr: 1 (0.2%). [68Ga]Ga-/[18F]F-PSMA-11/-1007 (n = 453 (96.0%)) demonstrates the highest detection rate, followed by [68Ga]Ga-FAPI-46 (n = 268 (56.8%))/2-[18F]FDG (n = 241 (51.1%)). Semiquantitative uptake was highest for [68Ga]Ga-/[18F]F-PSMA-11/-1007 (mean SUVmax (interquartile range): 22.7 (22.5), vs. [68Ga]Ga-FAPI-46 (7.7 (3.7)) and 2-[18F]FDG (6.8 (4.7)). Seven/three patients were retrospectively assigned to the PSMA-dominant/mixed phenotype. Median overall survival was significantly longer for patients who underwent [177Lu]Lu-PSMA-617 RLT and were retrospectively assigned to the PSMA-dominant phenotype (19.7 vs. 9.3 months). Through whole-body imaging, we identify considerable inter- and intra-patient heterogeneity of mCRPC and potential imaging phenotypes. Regarding uptake and tumour detection, [68Ga]Ga-/[18F]F-PSMA-11/-1007 was superior to [68Ga]Ga-FAPI-46 and 2-[18F]FDG, while the latter two were comparable. Patients who underwent [177Lu]Lu-PSMA-617 RLT based on clinical-decision making had a longer overall survival and could be assigned to the PSMA-dominant phenotype.

Pabst KM ，Mei R ，Lückerath K ，Hadaschik BA ，Kesch C ，Rawitzer J ，Kessler L ，Bodensieck LS ，Hamacher R ，Pomykala KL ，Fanti S ，Herrmann K ，Fendler WP ... -  《-》

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 ... -  《-》

[(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 ... -  《-》