FAP expression

Immunohistological assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing Sibrotuzumab as a promising therapeutic avenue for clinical treatment of esophageal cancer patients.

P2, N=60, Recruiting, SOFIE | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

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. 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.

FAP-positive fibroblasts may contribute to tumor stroma formation in early-stage lung adenocarcinoma, and this could influence the development of therapeutic strategies targeting FAP-positive CAFs for disrupting extracellular matrix formation.

We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.

This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.

Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy...However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact. Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.

Radiolabeled FAPI can improve the detection, staging, and assessment of treatment response in breast and the most common gynecologic malignancies, but the problem with normal hormone-responsive organs remains insurmountable. Compared to the diagnostic applications of FAPI, further research is needed for future therapeutic applications.

The FAP overexpression promoted proliferation and migration while inhibiting the apoptosis of HCC cells. The FAP overexpression promoted the progression of HCC by regulating the immunity to affect the prognosis of HCC patients, thereby serving as a poor prognostic marker for HCC patients.

In addition, PET imaging results were corroborated by immunohistochemical assessment. In conclusion, molecular imaging approach revealed the heterogeneous progression of tumor cells and tumor stroma of bone metastasis of prostate cancer, and further confirming the necessity of multi-molecular imaging in cancer imaging.

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). 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.

P1/2, N=32, Not yet recruiting, Lantheus Medical Imaging

However, the tumor uptake values from the bispecific tracers were still lower than those obtained from the monospecific tracers, PSMA-targeted &lsqb;68Ga]Ga-PSMA-617 and FAP-targeted &lsqb;68Ga]Ga-AV02070. Further investigations are needed to optimize the selection of linkers and targeted pharmacophores to improve the tumor uptake of bispecific PSMA/FAP tracers for prostate cancer imaging.

Notably, TGF-β, CDKs, and the Wnt pathway are affected. In conclusion, CAFs play a significant role in CRC and impact the TME throughout development.

The background uptake of [18F]FAPI is negligible. Moreover, the uptake of [18F]FAPI may not be affected by acute radiation pneumonitis compared to [18F]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.

ANO1 is a prognostic factor in patients with PC after radical resection. ANO1 may induce an immunosuppressive tumor microenvironment in PC in a paracrine manner, suggesting that ANO1 may be a novel therapeutic target.

The Glycine-Proline FAP-cleavable technology was directly benchmarked against linkers found in Adcetris™, Enhertu™, and Trodelvy™ structures by means of in vivo therapeutic experiments in mice bearing tumors with cellular or stromal FAP expression. OncoFAP-GlyPro-Exatecan and OncoFAP-GlyPro-MMAE emerged as the most efficacious anti-cancer therapeutics against FAP-positive cellular models. OncoFAP-GlyPro-MMAE exhibited a potent antitumor activity also against stromal models, and was therefore selected for clinical development.

P1/2, N=222, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.

We successfully prepared an [F]AlF-LNC1007 dual-targeting PET probe with comparable performances as [Ga]Ga-LNC1007. With prolonged tumor retention and tumor specificity, it produced good imaging quality in preclinical and clinical translational studies, indicating that [F]AlF-LNC1007 is a promising non-invasive tracer for detecting tumors expressing FAP and/or integrin aβ, with the prospect of clinical implementation.

Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to F-FDG.

[Ga]Ga-FAPI-04 PET is more efficient in assisting debulking surgery in ovarian cancer patients than MRI-DWI. Integrated [Ga]Ga-FAPI-04 PET/MR imaging is a potential method for planning debulking surgery in ovarian cancer patients.

The immunohistochemical staining of IPMNs and PDAC validates FAP as a biology-based stromal target for in vivo imaging. Increasing expression of FAP in lesions with a higher degree of malignancy matches the expectation of a stronger FAP expression in PDAC and HG IPMNs than in LG IPMNs and corroborates our previous findings of higher SUVs and a longer TTP in PDAC and HG IPMNs than in LG IPMNs.

Clinical &lsqb;Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUV), 12.17 ± 6.67) and distant metastases (SUV, 9.24 ± 4.28). In summary, &lsqb;Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to &lsqb;Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

Our study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength.

P=N/A, N=45, Not yet recruiting, UMC Utrecht

The pattern of invasion should be included in reporting for MOC due to the strong prognostic implications. We highlight the histological features that should be considered to improve reproducibility. FAP and THBS2 are associated with infiltrative invasion in MOC.

These findings demonstrate that the novel αFAP TMs are promising immunotheranostic tools to foster cancer imaging and treatment, paving the way for a more convenient, individualized, and safer treatment of cancer patients.

Such enhanced energy expenditure is associated with increased levels of norepinephrine (NE) and lipolysis in white adipose tissues, likely due to decreased expression of monoamine oxidase, a NE degradation enzyme, by Fap ATM. Collectively, our study identifies FAP as a previously unrecognized regulator of ATM function contributing to diet-induced obesity and metabolic inflammation and suggests FAP as a potential immunotherapeutic target against metabolic disorders.

Additionally, we found high detection rate and diagnostic accuracy, superior to those of F-FDG PET/CT. Ga-FAPI might become a powerful diagnostic tool for pancreatic cancer work-up.

High intratumoral FAP expression was associated with worse survival, suggesting that intratumoral FAP expression represents malignant progression in patients with IHCC.

To facilitate the clinical translation of [68Ga]FAPI-46 in PDAC, the current study seeks to implement a coherent strategy to mitigate risks and increase the probability of meeting FDA requirements and stakeholder expectations. The findings from this study could potentially serve as a foundation for a New Drug Application to the FDA.

Fluorescence imaging further validated the value of the probe in guiding surgical resection and achieving precise removal of the tumor and residual lesions. In a preclinical model, these attractive &lsqb;Ga]Ga-FAP-2286-ICG PET/NIR imaging acquired in head and neck cancer make it a promising FAP-targeted multimodal probe for clinical translation.

We integrated in vitro data with mathematical modeling to characterize the pharmacology of FAP-4-1BBL as a function of trimeric complex formation when combined with the T-cell engager cibisatamab. Depending on the dosing schedule and FAP-4-1BBL plasma: tumor distribution, doses between 2 and 145 mg could lead to maximum trimeric complex formation in the clinic. Due to the expected variability in both pharmacokinetic and FAP expression in the patient population, we predict that detecting a clear dose-response relationship would remain difficult without a large number of patients per dose level, highlighting that mathematical modeling techniques based on in vitro data could aid dose selection.

Postsurgical pathologic report verified the diagnosis of ectopic papillary thyroid carcinoma. High FAP expression in the tumor sample corresponded to its imaging manifestations.

Our study suggests that Om and As could enhance the immune system's ability to treat TNBC by improving the infiltration and increasing the anti-tumor function of TILs. This intervention may lead to a promising therapeutic direction for the treatment of TNBC.

SPECT imaging and biodistribution of &lsqb;Tc]Tc-tricine/EDDA-HYNIC-Glc-FAPT demonstrated sustained high tumor uptake in BALB/c nude mice bearing U87MG tumors for 6 h. It demonstrated a long-range retention characteristic and more rapid clearance ability from nontarget organs. Collectively, we successfully synthesized &lsqb;Tc]Tc-tricine/EDDA-HYNIC-Glc-FAPT and &lsqb;Tc]Tc-tricine-HYNIC-Glc-FAPT, and the excellent targeting properties of &lsqb;Tc]Tc-tricine/EDDA-HYNIC-Glc-FAPT suggest a potential diagnostic value in future clinical studies for advanced-stage FAP-expressing malignancies, especially in prognostic evaluation of tumors for it low price and convenient source.

The role of FGF20 in activating FGFR2/pFGFR2 and AKT/pAKT was validated in-vitro. In conclusion, we identify a unique FAP(+) CAF population that showed WNT signaling upregulation and increased FGF20 levels; while neighbor tumor cells show the upregulation/activation of FGFR2-PI3K/Akt signaling at the tumor invasive margin of EOCC tumors.

P1, N=60, Recruiting, Affiliated Hospital of North Sichuan Medical College

Although 18F-FDG PET showed abnormally increased tracer uptake in multiple nodal sites and organs, indicating the aggressiveness of the disease status, 18F-FAPI PET showed no obvious FAPI uptake in any of the FDG-avid lesions. Our case suggests that low expression of FAP in diffuse large B-cell lymphoma, as indicated by FAPI PET, might help determine a subgroup of patients with poorer outcome.