OBJECTIVE: Fibroblast activating protein is a promising target for tumor molecular imaging and therapy. Studies showed that fibroblast activating protein inhibitor (FAPI) radioactive tracers presented superiority over 18F-FDG PET/CT in the evaluation of various cancer types, including pancreatic cancer (PC). Therefore, we conducted this meta-analysis to evaluate and analyze the differences between 68Ga/18F-FAPI and 18F-FDG in PC, in order to provide evidence for the clinical application of FAPI PET imaging.
METHODS: In the current meta-analysis, original studies published as of January 1, 2024 were analyzed using radiolabeled FAPI as a diagnostic radioactive tracer and compared to 18F-FDG for PET in PC. Databases searched included pubmed and web of science, and subject headings searched included PC and FAPI. The quality of the enrolled studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies 2, and the meta-analysis was conducted using R language.
RESULTS: A total of seven studies including 322 patients compared the diagnostic performance of FAPI PET imaging and 18F-FDG PET/CT in PC. Overall, FAPI PET imaging showed higher pooled sensitivity (0.99 [95% CI: 0.97-1.00] vs. 0.84 [95% CI: 0.70-0.92]) and area under the curve (0.99 [95% CI: 0.98-1.00] vs. 0.91 [95% CI: 0.88-0.93]) than 18F-FDG PET/CT. The evidence showed that FAPI PET imaging is superior to 18F-FDG in pooled sensitivity to primary tumor, lymph node metastasis, and distant metastasis. Moreover, FAPI PET imaging improved TNM staging in 25% of PC patients and changed clinical management in 11.7% of PC patients compared to 18F-FDG.
CONCLUSIONS: FAPI PET imaging is superior to that of 18F-FDG in the detection of primary PC, nodal and distant metastases, TNM staging and clinical management.

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BACKGROUND: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy. All currently used FAPI rely on a linker-chelator complex attached to the \'inhibitor\'. We describe a new automated method of the direct attachment of the radioisotope to the inhibitor, resulting in a >50% MW reduction with the hope of an improved tumor-to-background ratio and tumor uptake.
METHODS: [18F]FluroFAPI was developed from a Sn precursor. This allowed for subsequent automated radioflourination. We obtained the biodistribution of [18F]FluroFAPI in rats, performed estimated human radiation dosimetry, and performed a 100× expected single dose toxicology analysis for eventual first-in-human experiments.
RESULTS: The synthesis of the Sn precursor for FluorFAPI and the automated synthesis of [18F]FluroFAPI was demonstrated. [18F]FluroFAPI had favorable estimated human radiation dosimetry, and demonstrated no adverse effects when injected at a dose of 100× that planned for [18F]FluroFAPI.
CONCLUSIONS: With the successful development of an automated synthesis of [18F]FluroFAPI, first-in-human testing can be planned with the hope of an improved tumor-to-background performance compared to other FAPI agents.

Formamidinium lead iodide (FAPI) represents the most promising perovskite for single junction solar cells, exhibiting an impressive performance when deposited in a controlled nitrogen environment. In order to foster the real-world application of this technology, the deposition of FAPI in ambient air is a highly desirable prospect, as it would reduce fabrication costs. This study demonstrates that the wettability of FAPI precursors on the hole transporting layers (HTL) used to fabricate inverted p-i-n solar cells is extremely poor in ambient air, hampering the realization of a perovskite active layer with good optoelectronic quality. To address this issue, herein, a double compatibilization method is developed, which results in the attainment of remarkable performance, exceeding 21%, representing one of the highest reported efficiencies for FAPI solar cells fabricated in humid ambient air. The incorporation of a small quantity of anionic surfactant, comprising a hydrocarbon tail and a polar headgroup, sodium dodecyl sulfate (SDS), in the perovskite solution and an ultrathin layer of alumina nanoparticles on the HTL, results in a significant improvement in the wettability of the FAPI solution. This enables the reproducible deposition of highly homogeneous perovskite films with complete coverage and excellent optical and optoelectronic quality. Furthermore, devices based on FAPI with SDS exhibit enhanced stability, retaining 98% of their initial efficiency after 40 h of continuous illumination.

99mTc-HFAPI can visualize fibroblast activation in hypertensive hearts. Myocardial work (MW) reflects the cardiac mechanical properties after accounting for the afterload in hypertensive patients. We investigated whether MW was associated with increased uptake of 99mTc-HFAPI. A total of 97 hypertensive patients and 41 healthy volunteers were prospectively recruited. Global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were analyzed. According to whether myocardial uptake of FAPI was higher than the adjacent blood pool, hypertensive patients were divided into two groups, namely: FAPI + and FAPI- group, respectively. GWI, GCW and GWE of the FAPI + group were lower than the FAPI- group. The value of GWW in the FAPI + group was higher than in the FAPI- group. Multiple regression analyses revealed GWI, GWW and GWE were independently associated with early myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, the best cutoff points for FAPI + of GWI, GWW and GWE were 1968.50 mmHg% (AUC: 0.687, 95% CI: 0.581-0.793, P = 0.002), 133.00 mmHg% (AUC: 0.778, 95% CI: 0.688-0.869, P < 0.001) and 95.07% (AUC: 0.813, 95% CI: 0.730-0.896, P < 0.001), respectively. GWI, GWW and GWE were impaired in hypertensive patients with cardiac 99mTc-HFAPI uptake and were associated with fibroblast activation in hypertensive hearts.

The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a 68Ga-FAPI46 PET observational trial (NCT04571086). Methods: Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the 68Ga-FAPI46 PET observational trial. All patients underwent 68Ga-FAPI46 PET/CT, contrast-enhanced CT, and 18F-FDG PET/CT. The primary study endpoint was the association of 68Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with 18F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI46 SUVmax or SUVpeak and histopathologic FAP expression was significant (SUVmax: r = 0.49, P = 0.037; SUVpeak: r = 0.51, P = 0.030).68Ga-FAPI46 and 18F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher 68Ga-FAPI46 than 18F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of 68Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for 68Ga-FAPI46 versus 18F-FDG.

The role of fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) is emerging for the assessment of non-oncological diseases, such as inflammatory and infectious diseases, even if the evidence in the literature is still in its initial phases. We conducted a systematic search of Scopus, PubMed/MEDLINE, Embase, and Cochrane library databases for studies published before 31 December 2023 reporting infectious and inflammatory disease imaging with FAPI PET/CT. We included twenty-one studies for a total of 1046 patients. The most frequent disease studied was lung interstitial disease, investigated in six studies for a total of 200 patients, followed by bone and joint diseases in two studies and 185 patients, IgG4-related disease in 53 patients, and Crohn\'s disease in 30 patients. Despite the heterogeneity of studies in terms of study design and technical features, FAPI PET/CT showed a high detection rate and diagnostic role. Moreover, when compared with 2-[18F]FDG PET/CT (n = 7 studies), FAPI PET/CT seems to have better diagnostic performances. The presence of chronic inflammation and tissue remodeling, typical of immune-mediated inflammatory conditions, may be the underlying mechanism of FAPI uptake.

Positron emission tomography (PET) plays a crucial role in breast cancer management. This review addresses the role of PET imaging in breast cancer care. We focus primarily on the utility of 18F-fluorodeoxyglucose (FDG) PET in staging, recurrence detection, and treatment response evaluation. Furthermore, we delve into the growing interest in precision therapy and the development of novel radiopharmaceuticals targeting tumor biology. This includes discussing the potential of PET/MRI and artificial intelligence in breast cancer imaging, offering insights into improved diagnostic accuracy and personalized treatment approaches.

BACKGROUND: Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
OBJECTIVE: This article is dedicated to comparing the diagnostic efficacy of FAPI PET and [18F]fluorodeoxyglucose (FDG) PET in the evaluation of primary tumors, lymph nodes, and distant metastases in pancreatic cancer.
METHODS: In this review, we conducted a systematic search of studies published in PubMed and Web of Science databases up to September 18, 2023. All included studies used radionuclide labeled FAPI and FDG as PET diagnostic tracers to evaluate their applicability in patients with pancreatic cancer.
RESULTS: The FAPI PET imaging group showed significantly higher sensitivity in the detection of primary lesions (1.000, [95% CI: 0.999-1.000]), lymph node metastases (0.624 [95% CI: 0.391-0.834]) and distant metastatic (0.965 [95% CI: 0.804-1.000]) in pancreatic cancer compared to the FDG PET imaging group (0.889 [95% CI: 0.788-0.966], 0.373 [95% CI: 0.163-0.606] and 0.889 [95% CI: 0.689-0.999], respectively). Furthermore, the maximum standardized uptake value (SUVmax) in FAPI PET imaging is significantly higher than that in FDG imaging for primary lesions (mean difference (MD) = 7.51, 95% CI: 5.34-9.67).
CONCLUSIONS: Compared with [18F]FDG PET/CT, FAPI PET imaging showed higher sensitivity, SUVmax. This method can be effectively utilized for the evaluation of pancreatic cancer.
CONCLUSIONS: Fibroblast activating protein inhibitor PET may be a better alternative to [18F]FDG in evaluating primary pancreatic cancer, lymph node metastases, and distant metastases.
CONCLUSIONS: Fibroblast activating protein inhibitor (FAPI) PET is compared with FDG PET for evaluating pancreatic cancer. Multiple radiolabeled FAPI variants have shown promising results in the diagnosis of pancreatic cancer. FAPI PET imaging effectively helps clinicians diagnose and stage pancreatic cancer.

BACKGROUND: [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.
METHODS: Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.
CONCLUSIONS: To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.
BACKGROUND: clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.