FAPI-PET Imaging: Advancing molecular imaging in oncology and fibrotic diseases.
Explore how FAPI-PET offers high-contrast imaging, theranostic potential, and
complementary insights to FDG-PET in both cancer and fibrotic disease management.
Molecular Imaging
Molecular imaging is a field of advanced medical imaging focusing on the non-invasive
visualization, characterization, and measurement of biological processes at a molecular and cellular level. Molecular imaging has a place across a variety of disciplines, most notably within oncology, but also the central nervous system, cardiovascular medicine, and thyroid disorders. Scientists and researchers utilize molecular imaging to study how molecular abnormalities build up and influence the development of diseases, which in turn informs diagnosis, staging, and therapeutic innovation. Molecular imaging techniques include fluorescence, bioluminescence, nuclear magnetic resonance, ultrasound waves, radiation, and positron emission tomography (PET), and single photon emissions computed tomography (SPECT).
FAPI as a promising biomarker
One promising biomarker for evaluation via positron emission tomography, specifically, is Fibroblast Activation Protein (FAP). FAP is a cell surface protein primarily expressed by activated fibroblasts, minimally expressed in normal adult tissue, it is also upregulated in carcinoma-associated fibroblasts within the tumor microenvironment and certain fibrotic diseases. Carcinoma-associated fibroblasts often constitute a large proportion of tumor mass but have the benefit of relative stability versus genetically unstable cancer cells, making it a compelling target for diagnosis and therapy. Although this target has been under investigation for over four decades, it was traditionally studied in the context of chemotherapy with very little success. More recent discoveries in the field of radiopharmaceuticals, particularly prostate-specific membrane antigen (PSMA)–targeted and somatostatin receptor (SSTR)–targeted therapies, have redirected research efforts towards exploring FAP as a novel target with theranostic potential. This growing clinical and research interest has led to a significant increase in research funding, and there are currently an estimated 168 clinical trials which mention FAP registered on clinicaltrials.gov.
What is FAPI-PET?
FAPI-PET = Fibroblast Activation Protein Inhibitor (FAPI) -based Positron Emission Tomography (PET). FAPI-PET is a subset of molecular imaging. Positron Emission Tomography, or PET, is a molecular imaging modality which use radiolabeled tracers to map specific biologic targets. FAPI-PET uses those PET radiolabeled tracers to selectively bind to Fibroblast Activation Protein, which is highly expressed in cancer-associated fibroblasts and fibrotic diseases, providing high-contrast images of tumor sites and other areas of disease-related fibroblast activity. FAPI-PET has been found to produce high-contrast images with low-background (which are typically easier to analyze), with better tumor delineation, and the ability to detect hidden lesions near or within tissues. That being said, research is ongoing to determine performance against specific tumor types and clinical scenarios.
Advantages of FAPI-PET
Advantages of this imaging modality include:
- High-contrast, low-background images
- Broad tumor applicability
- Fast uptake and clearance
- Potential applications in theranostics
- Utility in non-oncologic indications
- Favorable dosimetry and safety profile
Milestone applications and discoveries
Early analysis of FAPI-PET established its feasibility as a novel diagnostic and staging modality, with broad applications in oncology. Initially, several highly prevalent cancers presented with remarkably high uptake and image contrast across clinical research, followed by confirmation of FAPI-PET as an imaging biomarker for the detection of FAP-expressing tumors. Research is ongoing into specific tumor types, with promising results for pancreatic cancer, head and neck cancer, and gynecological cancers.
While FAPI-PET has shown a lot of promise in staging of various oncologic indications, many KOLs believe its highest potential lies within the realm of fibrotic diseases, which are characterized by the activation of fibroblasts, in which FAP plays a central role. Specific conditions including pulmonary fibrosis, renal fibrosis, and liver fibrosis are driven by activated fibroblasts. FAPI-PET tracers specifically bind to FAP, enabling visualization of fibrotic activity rather than just structural changes as done by CT/MRI. Research clearly identifies FAPI-PET as a promising imaging biomarker for fibrotic disease because it visualizes active fibroblast biology. FAP-targeted imaging may also provide a novel biomarker of LV remodeling that is complementary to existing techniques. We are also seeing a lot of good data emerge in rheumatoid arthritis.
FAPI-PET has more recently shown extremely promising theranostic applications, combining therapy with diagnostics in one single approach. Research continues to explore its role in targeted radionuclide therapies and personalized medicine approaches, particularly in tumors with high FAP expression.
FAPI-PET versus FDG-PET
Many of the aforementioned oncology studies seek to clarify the efficacy of FAPI-PET versus the standard imaging modality, Fluorodeoxyglucose-positron emission tomography (FDG-PET). Although many recent studies support the apparent advantages of FAPI-PET, a recent webinar entitled “FAPI-PET Imaging & Theranostics: A New Era in Targeting Cancer and Fibrotic Diseases”, hosted by leading experts and suppliers of advanced medical imaging, Perceptive Imaging, highlights the plausibility that these two imaging techniques are actually complementary. FAPI-PET’s capacity to visualize the tumor microenvironment is highly complementary to FDG-PET’s sensitivity to metabolic activity. Combining both modalities could therefore offer a more holistic view of tumor microbiology.
Conclusion
Recent FAPI-PET discoveries have solidified the key advantages of utilizing this advanced molecular imaging modality within both oncology and fibrotic disease, with potential applications across other therapeutic areas undergoing further investigation. Advantages include broad tumor applicability, fast uptake and clearance, favorable dosimetry and safety profile, and most notably, a markedly higher tumor-to-background contrast which enables better tumor delineation and detection of hidden lesions. A complementary approach to the standard FDG-PET, combining metabolic and microenvironmental insights could provide a more comprehensive and holistic assessment of disease and tumor microbiology. Moving forward, larger clinical trials, standardization of imaging protocols, and regulatory approvals will be critical to fully establish FAPI-PET as a routine tool in both oncology and fibrotic disease management, and further research is needed to realize the potential and personalized applications in the field of theranostics.
One imaging provider, Perceptive, bring over 15 years of experience in radiopharmaceutical trial imaging support, with proven industry leadership in radioligand therapy and a robust team of in-house clinicians, dosimetrists, and imaging scientists. Partnering with Perceptive ensures operational excellence from protocol development through to endpoint analysis and regulatory submission.
Contact an imaging solutions specialist today.
Resources
Science Direct. Molecular Imaging. https://www.sciencedirect.com/topics/neuroscience/molecular-imaging
Clinical Nuclear Medicine. Dual-Time Point 68 Ga-FAPI-04 PET/CT Improves Tumor Delineation and Cervical Lymph Node Metastasis Identification in Patients With Head and Neck Squamous Cell Carcinoma. https://pubmed.ncbi.nlm.nih.gov/39668486/
FEBS Journal. Phenotypic heterogeneity, stability and plasticity in tumor-promoting carcinoma- associated fibroblasts. https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15851
Journal of Nuclear Medicine. 68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with
Various Cancers. https://pubmed.ncbi.nlm.nih.gov/30072500/
Journal of Nuclear Medicine. 68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer. https://pubmed.ncbi.nlm.nih.gov/30954939/
The Lancet. [68Ga]Ga-FAPI-46 PET accuracy for cancer imaging with histopathology validation: a single-centre, single-arm, interventional, phase 2 trial. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00299-2/fulltet
Cancers (Basel). FAP-Directed Imaging and Therapy in Head and Neck Cancer of Unknown Primary. https://pmc.ncbi.nlm.nih.gov/articles/PMC12249064/
Molecular Imaging Biology. Prospective Comparison of [18F]FDG and [18F]AIF-FAPI-74
PET/CT in the Evaluation of Potentially Resectable Pancreatic Ductal Adenocarcinoma.
https://pubmed.ncbi.nlm.nih.gov/39365411/
Cancer Imaging. Head-to-head comparison of 18F-FDG and 68Ga-FAPI PET/CT in common gynecological malignancies. https://pubmed.ncbi.nlm.nih.gov/40022239/
Lancet Rheumatology. 68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study. https://pubmed.ncbi.nlm.nih.gov/38279381/
European Journal of Nuclear Medicine and Molecular Imaging. [68 Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease. https://pubmed.ncbi.nlm.nih.gov/34988624/
Molecular Imaging and Radionuclide Therapy. 68Ga-FAPI-04 PET/CT Findings in Patients with Liver Cirrhosis. https://pubmed.ncbi.nlm.nih.gov/37337827/
Journal of Nuclear Medicine. Cardiac Fibroblast Activation in Patients Early After Acute
Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome. https://pubmed.ncbi.nlm.nih.gov/35210301/
